A Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02087904
• Collaborator: (none)
• Enrollment: 350
• Arms: 4
• Actual Duration (Months): 30.3

Study Details

Study Description

Brief Summary

A Phase 2a, multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the safety, tolerability, efficacy and pharmacokinetic/pharmacodynamic effect of ABT-981 in patients with symptomatic, radiographic, and inflammatory knee osteoarthritis.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis; Medial Compartment Knee Osteoarthritis	Biological: ABT-981; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis
• Actual Study Start Date: Jun 4, 2014
• Actual Primary Completion Date: Jun 7, 2016
• Actual Study Completion Date: Dec 13, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-981 low dose 25 mg ABT-981 subcutaneous (SC) every 2 weeks (E2W)	Biological: ABT-981; Other Names: Lutikizumab
Experimental: ABT-981 medium dose 100 mg ABT-981 SC E2W	Biological: ABT-981; Other Names: Lutikizumab
Experimental: ABT-981 high dose 200 mg ABT-981 SC E2W	Biological: ABT-981; Other Names: Lutikizumab
Placebo Comparator: Placebo Placebo	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scores of the Index Knee at Week 16 [Baseline, Week 16]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.

2. Change From Baseline in Quantitative Synovitis of the Index Knee at Week 26 [Baseline, Week 26]

   Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness.

3. Change From Baseline in Effusion Volume of the Index Knee at Week 26 [Baseline, Week 26]

4. Change From Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26 [Baseline, Week 26]

   Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), < 33% of maximum estimated distention (1), 33% - 66% of maximum estimated distention (2), or > 66% of maximum estimated distention (3).

Secondary Outcome Measures

1. Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16 [Baseline, Week 16]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

2. Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26 [Baseline, Week 26]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

3. Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52 [Baseline, Week 52]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.

4. Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26 [Baseline, Week 26]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.

5. Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52 [Baseline, Week 52]

   The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.

6. Change From Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26 [Baseline, Week 26]

   BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe).

7. Change From Baseline in Global Total BML Score of the Index Knee MRI at Week 52 [Baseline, Week 52]

   BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe).

8. Change From Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16 [Baseline, Week 16]

   The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).

9. Change From Baseline in Index Knee ICOAP Scores at Week 26 [Baseline, Week 26]

   The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).

10. Change From Baseline in Index Knee ICOAP Scores at Week 52 [Baseline, Week 52]

    The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).

11. Change From Baseline In Index Knee Pain Intensity at Week 16 [Baseline, Week 16]

    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.

12. Change From Baseline In Index Knee Pain Intensity at Week 26 [Baseline, Week 26]

    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.

13. Change From Baseline In Index Knee Pain Intensity at Week 52 [Baseline, Week 52]

    The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.

14. Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16 [Baseline, Week 16]

    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.

15. Change From Baseline in PGA of Arthritis of the Index Knee at Week 26 [Baseline, Week 26]

    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.

16. Change From Baseline in PGA of Arthritis of the Index Knee at Week 52 [Baseline, Week 52]

    The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.

17. Change From Baseline in Cartilage Volume of the Index Knee at Week 26 [Baseline, Week 26]

    Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

18. Change From Baseline in Cartilage Volume of the Index Knee at Week 52 [Baseline, Week 52]

    Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

19. Change From Baseline in Cartilage Thickness of the Index Knee at Week 26 [Baseline, Week 26]

    Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

20. Change From Baseline in Cartilage Thickness of the Index Knee at Week 52 [Baseline, Week 52]

    Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.

21. Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16 [Week 16]

    Percentage of participants classified as OMERACT-OARSI responders at Week 16. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

22. Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 26 [Week 26]

    Percentage of participants classified as OMERACT-OARSI responders at Week 26. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

23. Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 52 [Week 52]

    Percentage of participants classified as OMERACT-OARSI responders at Week 52. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Radiographic knee osteoarthritis with Kellgren-Lawrence Grade 2 or 3

2. Body Mass Index (BMI) 18-34 kg/m2

3. One or more clinical signs and symptoms of active inflammation in the index knee

Exclusion Criteria:

1. History of allergic reaction to any constituents of the study drug, or to any Immunoglobulin G (IgG)-containing product

2. History of anaphylactic reaction to any agent

3. Significant trauma or surgery to the index knee

4. Severe knee malalignment

5. Any uncontrolled medical illness or an unstable treatment or therapy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Chair: Marc Levesque, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02087904
• Other Study ID Numbers: M13-741; 2013-003467-60
• First Posted: Mar 14, 2014
• Last Update Posted: Aug 28, 2019
• Last Verified: Jan 1, 2017

• Keywords provided by AbbVie: Osteoarthritis; Synovitis; Knee; Pain
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Pre-assignment Detail	The study included a screening period (approximately 45 days prior to first study drug dose) and a washout period (5 half-lives of the longest acting analgesic used, or 48 hours, whichever was longer, in which all standard of care analgesic medications were discontinued prior to the first study drug dose).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Period Title: Overall Study
STARTED	85	89	87	89
COMPLETED	60	70	65	64
NOT COMPLETED	25	19	22	25

Baseline Characteristics

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg	Total
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W	Total of all reporting groups
Overall Participants	85	89	85	88	347
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.53 (8.850)	61.63 (7.546)	60.21 (8.194)	59.05 (10.273)	60.11 (8.792)
Sex: Female, Male (Count of Participants)
Female	52 61.2%	63 70.8%	53 62.4%	57 64.8%	225 64.8%
Male	33 38.8%	26 29.2%	32 37.6%	31 35.2%	122 35.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scores of the Index Knee at Week 16
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, Last observation carried forward (LOCF; missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	88
Least Squares Mean (95% Confidence Interval) [score on a scale]	-8.9	-9.2	-11.8	-10.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.834
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and Kellgren-Lawrence (K-L) grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -3.13 to 2.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -5.73 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.415
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -4.00 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Quantitative Synovitis of the Index Knee at Week 26
Description	Change in synovitis of the index knee was evaluated using quantitative magnetic resonance imaging (MRI) measurements. MRI quantitative synovitis of the index knee was defined by mean synovial membrane thickness.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	59	65	59	63
Least Squares Mean (95% Confidence Interval) [mm]	-0.05	0.01	-0.08	0.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.021 to 0.141
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.056
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.159
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.023 to 0.139
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline in Effusion Volume of the Index Knee at Week 26
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	60	69	67	68
Least Squares Mean (95% Confidence Interval) [mL]	0.03	0.26	-1.04	-1.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.897
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -3.193 to 3.642
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.542
	Comments	P-value for test of difference between ABT-981 100 dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.07
	Confidence Interval	(2-Sided) 95%; -4.515 to 2.377
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.385
	Comments	P-value for test of difference between ABT-981 200 dose group and Placebo at each post-baseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.52
	Confidence Interval	(2-Sided) 95%; -4.95 to 1.916
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) Semi-Quantitative Synovitis/Effusion Score of the Index Knee at Week 26
Description	Semi-quantitative synovitis/effusion volume WORMS scores were scored as normal (0), < 33% of maximum estimated distention (1), 33% - 66% of maximum estimated distention (2), or > 66% of maximum estimated distention (3).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	70	76	70	75
Least Squares Mean (95% Confidence Interval) [score on a scale]	0.07	-0.01	-0.08	-0.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.384
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.249 to 0.096
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.324 to 0.026
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.314 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 16
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Modified intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	87
Least Squares Mean (95% Confidence Interval) [score on a scale]	-28.7	-29.8	-36.3	-32.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.818
	Comments	P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -10.22 to 8.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.109
	Comments	P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.6
	Confidence Interval	(2-Sided) 95%; -16.83 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.465
	Comments	P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -12.58 to 5.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 26
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	87
Least Squares Mean (95% Confidence Interval) [score on a scale]	-29.7	-31.8	-38.9	-36.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.666
	Comments	P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -11.76 to 7.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments	P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.2
	Confidence Interval	(2-Sided) 95%; -18.95 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments	P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) 95%; -16.84 to 2.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Scores of the Index Knee at Week 52
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) NRS. The WOMAC physical function subscale score was 0 (normal) to 170 (least physical function). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	87
Least Squares Mean (95% Confidence Interval) [score on a scale]	-32.9	-36.1	-38.7	-39.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments	P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -14.03 to 7.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.295
	Comments	P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) 95%; -16.77 to 5.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments	P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.8
	Confidence Interval	(2-Sided) 95%; -17.63 to 4.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 26
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified intent to Treat population: all subjects who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	88
Least Squares Mean (95% Confidence Interval) [score on a scale]	-9.2	-9.8	-11.9	-11.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.664
	Comments	P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -3.58 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.075
	Comments	P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -5.67 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments	P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -5.33 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Scores of the Index Knee at Week 52
Description	The WOMAC was developed to assess pain, stiffness, and physical function in subjects with hip and/or knee osteoarthritis. The WOMAC consists of 24 items divided into 3 subscales: Pain (5 items); Stiffness (2 items); and Physical Function (17 items). Each item is rated on an 11-point (0 to 10) numerical rating scale (NRS). The pain sub-score has a range of 0 (no pain) to 50 (maximum pain). A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified intent to Treat population: all participants who received at least 1 dose of study drug, LOCF (missing responses were imputed by calculation based on the last non-missing post-baseline component values).

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	88
Least Squares Mean (95% Confidence Interval) [score on a scale]	-10.0	-11.0	-12.1	-12.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments	P-value for test of difference between ABT-981 25 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -4.26 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.186
	Comments	P-value for test of difference between ABT-981 100 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -5.39 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.157
	Comments	P-value for test of difference between ABT-981 200 mg dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment, age, K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -5.46 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Global Total Bone Marrow Lesion (BML) Score of the Index Knee Magnetic Resonance Imaging (MRI) at Week 26
Description	BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	69	76	69	75
Least Squares Mean (95% Confidence Interval) [score on a scale]	0.1	0.3	-0.0	0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.319
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.966
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -0.45 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Global Total BML Score of the Index Knee MRI at Week 52
Description	BMLs in 15 regions were measured with MRI, and graded as 0 (normal), 1 (mild; < 25% of region), 2 (moderate; 25% - 50% of region), or 3 (severe; > 50% of region). The global total BML score was the sum of the 15 component scores, and ranged from 0 (normal) to 45 (severe).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	56	66	61	66
Least Squares Mean (95% Confidence Interval) [score on a scale]	0.1	0.2	0.1	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.602
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.953
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -0.55 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.61 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Index Knee Intermittent and Constant Osteoarthritis Pain (ICOAP) Scores at Week 16
Description	The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	75	84	76	77
Intermittent Pain	-20.2	-19.5	-21.3	-18.8
Constant Pain	-18.6	-17.7	-24.2	-20.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.804
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -4.91 to 6.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.699
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -6.9 to 4.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.636
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -4.37 to 7.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -4.91 to 6.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.6
	Confidence Interval	(2-Sided) 95%; -11.55 to 0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.649
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -7.34 to 4.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Index Knee ICOAP Scores at Week 26
Description	The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all subjects who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	68	75	72	73
Intermittent Pain	-18.7	-19.7	-21.3	-21.7
Constant Pain	-19.6	-18.8	-21.6	-22.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1
	Confidence Interval	(2-Sided) 95%; -7.14 to 5.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.409
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -8.82 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.338
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3
	Confidence Interval	(2-Sided) 95%; -9.24 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.817
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -5.59 to 7.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.544
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2
	Confidence Interval	(2-Sided) 95%; -8.37 to 4.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.437
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -8.91 to 3.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in Index Knee ICOAP Scores at Week 52
Description	The ICOAP is a multidimensional osteoarthritis-specific measure designed to comprehensively evaluate the pain experience in patients with hip or knee osteoarthritis. The ICOAP includes 11 items (5 constant pain items; 6 intermittent pain items). Each item is rated on a 0 to 4 point scale with a 7-day recall period. The raw maximum intermittent pain score ranges from 0 to 24, transformed to a reported scale of 0 (no pain) to 100 (worst pain). The raw maximum constant pain score ranges from 0 to 20, transformed to a reported scale of 0 (no pain) to 100 (worst pain).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	58	70	66	66
Intermittent Pain	-23.2	-25.4	-23.6	-27.2
Constant Pain	-20.6	-21.8	-25.2	-29.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.545
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -9.31 to 4.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.909
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -7.65 to 6.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Intermittent pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -11.23 to 3.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.732
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -8.42 to 5.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.216
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.6
	Confidence Interval	(2-Sided) 95%; -11.86 to 2.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Constant pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.2
	Confidence Interval	(2-Sided) 95%; -16.42 to -1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline In Index Knee Pain Intensity at Week 16
Description	The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	75	84	77	77
7-Day Recall Period	-2.4	-2.4	-2.7	-2.1
Activity Pain	-2.3	-2.4	-2.7	-2.1
Performance Pain (Before)	-2.4	-2.1	-2.5	-2.1
Performance Pain (After)	-2.6	-2.4	-2.7	-2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.874
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.451
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.86 to 0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.331
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.932
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.73 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.344
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.07 to 0.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.489
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.498
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.637
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.367
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.51 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.776
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.76 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.387
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline In Index Knee Pain Intensity at Week 26
Description	The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	68	75	73	73
7-Day Recall Period	-2.2	-2.4	-2.8	-2.5
Activity Pain	-2.5	-2.5	-2.8	-2.5
Performance Pain (Before)	-2.2	-2.2	-2.6	-2.7
Performance Pain (After)	-2.5	-2.4	-3.0	-2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.661
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.86 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.122
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.26 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.892
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.85 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.433
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.12 to 0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.957
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.68 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.222
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.13 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.209
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.15 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.813
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.62 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.135
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.25 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.679
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.85 to 0.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Change From Baseline In Index Knee Pain Intensity at Week 52
Description	The index knee pain intensity was assessed in 3 different ways using an 11 -point NRS (0 to 10 points representing 'no pain' to 'worst possible pain'). Subjects were asked to enter: 1) average pain intensity during the past week (7-day recall period); 2) the worst pain during activity over the past 24 hours; 3) pain intensity before and after a 40 meter walk (performance pain, before and after). The 40 meter fast paced walk test is a test of short distance walking activity, walking speed over short distances and changing direction during walking. Individuals taking the test should walk as quickly but as safely as possible, without running, along a walkway and then turn around, and repeat again for a total distance of 40 m (132 feet). The total time taken to walk the 40 meters is recorded.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	58	70	67	66
7-Day Recall Period	-2.9	-2.9	-2.9	-3.1
Activity Pain	-2.8	-3.0	-3.2	-3.0
Performance Pain (Before)	-2.6	-2.7	-3.0	-2.9
Performance Pain (After)	-2.9	-3.0	-3.4	-3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.978
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.76 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.925
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.75 to 0.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	7-day recall period
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.659
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.633
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.23 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Activity pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.663
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.696
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.89 to 0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.16 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (before)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.357
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.761
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.87 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.02 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Performance pain (after)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.513
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.02 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Change From Baseline in Patient Global Assessment (PGA) of Arthritis of the Index Knee at Week 16
Description	The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	75	84	77	77
Least Squares Mean (95% Confidence Interval) [units on a scale]	-2.5	-2.4	-2.9	-2.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.728
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.52 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.219
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.06 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.673
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.79 to 0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in PGA of Arthritis of the Index Knee at Week 26
Description	The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	68	75	73	73
Least Squares Mean (95% Confidence Interval) [units on a scale]	-2.4	-2.4	-3.0	-2.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.984
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.73 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.26 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.527
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.96 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline in PGA of Arthritis of the Index Knee at Week 52
Description	The PGA is a single item for evaluating overall osteoarthritis disease activity. PGA is assessed using an 11-point NRS of 0 to 10 points (representing best to worst disease status, respectively), with a 7-day recall period.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	58	70	67	66
Least Squares Mean (95% Confidence Interval) [units on a scale]	-3.0	-2.9	-3.2	-3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.836
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.71 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.738
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.94 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.22 to 0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline in Cartilage Volume of the Index Knee at Week 26
Description	Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	58	65	53	66
Global Knee	-326.0	-325.5	-322.4	-359.0
Medial Central Condyle + Plateau	-59.1	-54.9	-50.1	-57.5
Medial Condyle + Plateau	-128.6	-126.5	-124.5	-114.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -101.59 to 102.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.948
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -103.95 to 111.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.523
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-33.1
	Confidence Interval	(2-Sided) 95%; -134.76 to 68.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.799
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; -28.47 to 36.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.609
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.0
	Confidence Interval	(2-Sided) 95%; -25.62 to 43.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.923
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -30.97 to 34.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.937
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -49.88 to 54.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.882
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 95%; -50.68 to 58.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.602
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.8
	Confidence Interval	(2-Sided) 95%; -38.05 to 65.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Change From Baseline in Cartilage Volume of the Index Knee at Week 52
Description	Cartilage volume of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	49	57	50	56
Global Knee	-557.0	-598.7	-554.3	-583.1
Medial Central Condyle + Plateau	-101.2	-126.3	-90.1	-113.0
Medial Condyle + Plateau	-214.7	-255.0	-190.3	-242.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.554
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-41.7
	Confidence Interval	(2-Sided) 95%; -180.49 to 97.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -140.86 to 146.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.713
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-26.1
	Confidence Interval	(2-Sided) 95%; -165.47 to 113.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.272
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.1
	Confidence Interval	(2-Sided) 95%; -70.12 to 19.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -35.63 to 57.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.8
	Confidence Interval	(2-Sided) 95%; -56.94 to 33.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.319
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-40.3
	Confidence Interval	(2-Sided) 95%; -119.88 to 39.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.4
	Confidence Interval	(2-Sided) 95%; -58.05 to 106.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.489
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-28.1
	Confidence Interval	(2-Sided) 95%; -107.97 to 51.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline in Cartilage Thickness of the Index Knee at Week 26
Description	Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	58	65	53	66
Global Knee	-0.047	-0.047	-0.048	-0.052
Medial Central Condyle + Plateau	-0.085	-0.077	-0.074	-0.076
Medial Condyle + Plateau	-0.046	-0.045	-0.047	-0.044

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.972
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.015 to 0.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.929
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.001
	Confidence Interval	(2-Sided) 95%; -0.017 to 0.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.543
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.005
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.752
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.008
	Confidence Interval	(2-Sided) 95%; -0.043 to 0.059
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.011
	Confidence Interval	(2-Sided) 95%; -0.042 to 0.064
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.71
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.041 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.965
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.019 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.885
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95%; -0.022 to 0.019
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.887
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.001
	Confidence Interval	(2-Sided) 95%; -0.018 to 0.021
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change From Baseline in Cartilage Thickness of the Index Knee at Week 52
Description	Cartilage thickness of the global knee, the medial central condyle + plateau, and the medial condyle + plateau was measured using MRI.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, observed cases.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	49	57	50	56
Global Knee	-0.081	-0.085	-0.081	-0.083
Medial Central Condyle + Plateau	-0.136	-0.176	-0.113	-0.141
Medial Condyle + Plateau	-0.084	-0.096	-0.073	-0.087

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.619
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.005
	Confidence Interval	(2-Sided) 95%; -0.024 to 0.014
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.952
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.001
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.019
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Global knee
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.765
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.003
	Confidence Interval	(2-Sided) 95%; -0.022 to 0.016
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.535
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.023
	Confidence Interval	(2-Sided) 95%; -0.049 to 0.094
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial central condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.866
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.006
	Confidence Interval	(2-Sided) 95%; -0.076 to 0.064
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.413
	Comments	P-value for test of difference between ABT-981 25 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.012
	Confidence Interval	(2-Sided) 95%; -0.041 to 0.017
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.445
	Comments	P-value for test of difference between ABT-981 100 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.012
	Confidence Interval	(2-Sided) 95%; -0.018 to 0.042
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments	Medial condyle + plateau
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.835
	Comments	P-value for test of difference between ABT-981 200 mg dose group and Placebo at each postbaseline time point was from an ANCOVA model with treatment, age, and K-L grade as the main factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.003
	Confidence Interval	(2-Sided) 95%; -0.032 to 0.026
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 16
Description	Percentage of participants classified as OMERACT-OARSI responders at Week 16. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	87
Number (95% Confidence Interval) [percentage of participants]	60.0 70.6%	67.0 75.3%	72.6 85.4%	65.5 74.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.311
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	7.0
	Confidence Interval	(2-Sided) 95%; -7.3 to 21.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.435
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; -8.9 to 19.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.435
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	5.5
	Confidence Interval	(2-Sided) 95%; -8.9 to 19.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 26
Description	Percentage of participants classified as OMERACT-OARSI responders at Week 26. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	88
Number (95% Confidence Interval) [percentage of participants]	62.4 73.4%	64.8 72.8%	66.7 78.5%	72.7 82.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.744
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 95%; -11.9 to 16.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.581
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -10.1 to 18.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.146
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	10.4
	Confidence Interval	(2-Sided) 95%; -3.5 to 24.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT/OARSI) Response Rate at Week 52
Description	Percentage of participants classified as OMERACT-OARSI responders at Week 52. A subject was considered an OMERACT-OARSI responder if any of the following 3 criteria were met: 1. WOMAC Pain (in 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 2. WOMAC Function (in normalized 0 - 100 scale) improvement ≥ 50% and absolute reduction ≥ 20 as compared to the baseline; or 3. At least 2 of the following 3 are met: WOMAC Pain improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; WOMAC Function improvement ≥ 20% and absolute reduction (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline; PGA improvement ≥ 20% and absolute change (in normalized 0 - 100 scale) ≥ 10 as compared to the baseline. Response rate 95% confidence interval based on normal approximation.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat population: all participants who received at least 1 dose of study drug, LOCF.

Arm/Group Title	Placebo	ABT-981 25 mg	ABT-981 100 mg	ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W	25 mg ABT-981 SC E2W	100 mg ABT-981 SC E2W	200 mg ABT-981 SC E2W
Measure Participants	85	88	84	88
Number (95% Confidence Interval) [percentage of participants]	70.6 83.1%	69.3 77.9%	71.4 84%	72.7 82.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 25 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.824
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -14.9 to 12.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 100 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.964
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -12.8 to 14.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, ABT-981 200 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.763
	Comments	P-value for test of difference between each ABT-981 dose group and Placebo was from a Cochran-Mantel-Haenszel test using age group and K-L grade as stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -11.3 to 15.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	up to Week 52 (or last dose of study drug) plus 70 days
Adverse Event Reporting Description	Safety population: all participants who took at least one dose of study drug.
Arm/Group Title	Placebo		ABT-981 25 mg		ABT-981 100 mg		ABT-981 200 mg
Arm/Group Description	Matching placebo SC E2W		25 mg ABT-981 SC E2W		100 mg ABT-981 SC E2W		200 mg ABT-981 SC E2W
All Cause Mortality
	Placebo		ABT-981 25 mg		ABT-981 100 mg		ABT-981 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		ABT-981 25 mg		ABT-981 100 mg		ABT-981 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/85 (9.4%)		11/89 (12.4%)		8/85 (9.4%)		4/88 (4.5%)
Endocrine disorders
ADRENAL HAEMORRHAGE	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
Gastrointestinal disorders
COLITIS	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
ENTERITIS	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
ENTEROCOLITIS	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
PANCREATITIS	0/85 (0%)		0/89 (0%)		0/85 (0%)		1/88 (1.1%)
SMALL INTESTINAL OBSTRUCTION	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	0/85 (0%)		1/89 (1.1%)		1/85 (1.2%)		0/88 (0%)
LIVER DISORDER	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
Infections and infestations
APPENDICITIS	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
DIVERTICULITIS	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
PERITONITIS	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
PNEUMONIA	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
URINARY TRACT INFECTION	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
Injury, poisoning and procedural complications
ANKLE FRACTURE	1/85 (1.2%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
CERVICAL VERTEBRAL FRACTURE	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
CONCUSSION	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
FALL	2/85 (2.4%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
HIP FRACTURE	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
HUMERUS FRACTURE	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
JOINT INJURY	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
LACERATION	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
PROCEDURAL INTESTINAL PERFORATION	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
RADIUS FRACTURE	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
ROAD TRAFFIC ACCIDENT	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		1/88 (1.1%)
SKULL FRACTURE	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
TIBIA FRACTURE	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
UPPER LIMB FRACTURE	1/85 (1.2%)		0/89 (0%)		0/85 (0%)		0/88 (0%)
Musculoskeletal and connective tissue disorders
BACK PAIN	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
OSTEOARTHRITIS	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
COLON ADENOMA	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
INVASIVE DUCTAL BREAST CARCINOMA	0/85 (0%)		0/89 (0%)		0/85 (0%)		1/88 (1.1%)
LUNG CANCER METASTATIC	0/85 (0%)		0/89 (0%)		0/85 (0%)		1/88 (1.1%)
Nervous system disorders
AQUEDUCTAL STENOSIS	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
BRAIN OEDEMA	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
CEREBRAL HAEMORRHAGE	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
HYDROCEPHALUS	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
PARKINSON'S DISEASE	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
SEIZURE	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
SYNCOPE	0/85 (0%)		0/89 (0%)		0/85 (0%)		1/88 (1.1%)
Renal and urinary disorders
NEPHROLITHIASIS	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
Respiratory, thoracic and mediastinal disorders
ALVEOLITIS ALLERGIC	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
ASTHMA	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
DYSPNOEA	0/85 (0%)		0/89 (0%)		1/85 (1.2%)		0/88 (0%)
Vascular disorders
HYPERTENSION	0/85 (0%)		1/89 (1.1%)		0/85 (0%)		0/88 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		ABT-981 25 mg		ABT-981 100 mg		ABT-981 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/85 (77.6%)		63/89 (70.8%)		65/85 (76.5%)		75/88 (85.2%)
Blood and lymphatic system disorders
NEUTROPENIA	1/85 (1.2%)		12/89 (13.5%)		12/85 (14.1%)		21/88 (23.9%)
Gastrointestinal disorders
DIARRHOEA	7/85 (8.2%)		6/89 (6.7%)		5/85 (5.9%)		9/88 (10.2%)
NAUSEA	3/85 (3.5%)		4/89 (4.5%)		6/85 (7.1%)		6/88 (6.8%)
General disorders
FATIGUE	12/85 (14.1%)		4/89 (4.5%)		5/85 (5.9%)		7/88 (8%)
INJECTION SITE ERYTHEMA	1/85 (1.2%)		4/89 (4.5%)		7/85 (8.2%)		5/88 (5.7%)
INJECTION SITE PAIN	7/85 (8.2%)		2/89 (2.2%)		2/85 (2.4%)		1/88 (1.1%)
INJECTION SITE RASH	3/85 (3.5%)		3/89 (3.4%)		7/85 (8.2%)		8/88 (9.1%)
INJECTION SITE REACTION	0/85 (0%)		6/89 (6.7%)		8/85 (9.4%)		12/88 (13.6%)
PAIN	6/85 (7.1%)		3/89 (3.4%)		4/85 (4.7%)		4/88 (4.5%)
Infections and infestations
BRONCHITIS	2/85 (2.4%)		5/89 (5.6%)		1/85 (1.2%)		4/88 (4.5%)
INFLUENZA	10/85 (11.8%)		2/89 (2.2%)		5/85 (5.9%)		4/88 (4.5%)
NASOPHARYNGITIS	16/85 (18.8%)		9/89 (10.1%)		13/85 (15.3%)		17/88 (19.3%)
SINUSITIS	1/85 (1.2%)		5/89 (5.6%)		3/85 (3.5%)		3/88 (3.4%)
UPPER RESPIRATORY TRACT INFECTION	8/85 (9.4%)		8/89 (9%)		7/85 (8.2%)		12/88 (13.6%)
URINARY TRACT INFECTION	4/85 (4.7%)		3/89 (3.4%)		5/85 (5.9%)		8/88 (9.1%)
Injury, poisoning and procedural complications
CONTUSION	3/85 (3.5%)		9/89 (10.1%)		2/85 (2.4%)		5/88 (5.7%)
FALL	3/85 (3.5%)		5/89 (5.6%)		3/85 (3.5%)		8/88 (9.1%)
LIGAMENT SPRAIN	3/85 (3.5%)		6/89 (6.7%)		2/85 (2.4%)		2/88 (2.3%)
Investigations
NEUTROPHIL COUNT DECREASED	1/85 (1.2%)		3/89 (3.4%)		13/85 (15.3%)		13/88 (14.8%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	16/85 (18.8%)		16/89 (18%)		19/85 (22.4%)		14/88 (15.9%)
BACK PAIN	14/85 (16.5%)		8/89 (9%)		11/85 (12.9%)		14/88 (15.9%)
MUSCULOSKELETAL PAIN	5/85 (5.9%)		5/89 (5.6%)		4/85 (4.7%)		4/88 (4.5%)
MYALGIA	1/85 (1.2%)		2/89 (2.2%)		3/85 (3.5%)		9/88 (10.2%)
PAIN IN EXTREMITY	6/85 (7.1%)		5/89 (5.6%)		7/85 (8.2%)		5/88 (5.7%)
Nervous system disorders
DIZZINESS	1/85 (1.2%)		3/89 (3.4%)		6/85 (7.1%)		3/88 (3.4%)
HEADACHE	22/85 (25.9%)		14/89 (15.7%)		14/85 (16.5%)		21/88 (23.9%)
Respiratory, thoracic and mediastinal disorders
COUGH	5/85 (5.9%)		7/89 (7.9%)		5/85 (5.9%)		5/88 (5.7%)
OROPHARYNGEAL PAIN	2/85 (2.4%)		4/89 (4.5%)		5/85 (5.9%)		7/88 (8%)
Skin and subcutaneous tissue disorders
PRURITUS	0/85 (0%)		6/89 (6.7%)		5/85 (5.9%)		4/88 (4.5%)
RASH	3/85 (3.5%)		2/89 (2.2%)		6/85 (7.1%)		4/88 (4.5%)
Vascular disorders
HYPERTENSION	6/85 (7.1%)		7/89 (7.9%)		5/85 (5.9%)		1/88 (1.1%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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