FACT CLBP 1: Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03285646
• Collaborator: Teva Pharmaceutical Industries, Ltd. (Industry)
• Enrollment: 63
• Locations: 56
• Arms: 2
• Actual Duration (Months): 18
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the efficacy of fasinumab in relieving Chronic low back pain (CLBP) as compared to placebo in participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and Osteoarthritis (OA) of the knee or hip when treated for up to 16 weeks. The secondary objectives of the study are: To evaluate the safety and tolerability of fasinumab compared to placebo when participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks; To characterize the concentrations of fasinumab in serum over time when participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks; To evaluate the immunogenicity of fasinumab when treated for up to 16 weeks in participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip.

Condition or Disease	Intervention/Treatment	Phase
Chronic Low Back Pain; Osteoarthritis	Drug: Fasinumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee
• Actual Study Start Date: Oct 30, 2017
• Actual Primary Completion Date: May 5, 2018
• Actual Study Completion Date: May 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fasinumab Subcutaneous (SC) every 4 weeks (Q4W)	Drug: Fasinumab; Subcutaneous (SC) every 4 weeks (Q4W); Other Names: REGN475
Experimental: Placebo SC every 4 weeks	Drug: Placebo; Subcutaneous (SC) every 4 weeks (Q4W)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score [Week 1, Week 2, Week 4, Week 8, Week 12, Week 16]

   Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain.

Secondary Outcome Measures

1. Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score [Week 2, Week 4, Week 8, Week 12, Week 16]

   The RMDQ is a self-administered, health status measure for lower back pain (LBP). It measures pain and function using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores are indicative of better function.

2. Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score [Week 2, Week 4, Week 8, Week 12, Week 16]

   The PGA of LBP is a participant assessed 5 point Likert scale of LBP ranging from 1-5 where 1 = very well; 2 = well; 3 = fair; 4 = poor; and 5 = very poor.

3. Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score [Week 16]

   Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain.

4. Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score [Week 2, Week 4, Week 8, Week 12, Week 16]

   The BPI-sf is a self-administered questionnaire for participants to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function. With a recall period of 24 hours, the questionnaire contains the front and back body diagrams, the 4 pain severity items and 7 pain interference items rated on 0-10 scale; total interference score ranges from 0-10 (0, does not interfere; 10 completely interferes), and the question about percentage of pain relief by analgesics. The BPI pain interference is typically scored as the mean of the 7 interference items.

5. Number of Adjudicated Arthropathy (AA) Events [Up to Week 36]

   Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.

6. Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria [Up to Week 36]

   Destructive arthropathy (DA) is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive Osteoarthritis type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis.

7. Number of Treatment-Emergent Adverse Events (TEAEs) [Up to Week 16]

   Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period.

8. Number of Sympathetic Nervous System (SNS) Dysfunction Events [Up to Week 36]

   Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.

9. Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation [Up to Week 36]

   Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation.

10. Number of All-Cause Joint Replacement (JR) Surgery Events [Up to Week 36]

    All joint replacement surgery events regardless of cause.

11. Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug [Up to Week 64]

    An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (week 12) to evaluate the number of participants who had undergone or were scheduled for JR surgery.

12. Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay [16 Weeks]

    Samples for Anti-Drug Antibody (ADA) evaluation were collected at baseline and at subsequent study visits. ADA variables include ADA status (+ or -) and titer as follows: Total participants negative in the ADA assay at all time points analyzed. Pre-existing immunoreactivity - positive response at baseline with all post-dose results negative, or a positive response at baseline with all post-dose responses less than 9-fold over baseline titer levels. Treatment emergent - post-dose positive result when baseline results were negative. Persistent - A positive result detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period, with no negative results in-between. Indeterminate - A positive result at the last collection time point analyzed only. Transient - Not persistent or indeterminate regardless of any missing samples. Treatment boosted - any post-dose positive result at least 9-fold over the baseline level when baseline is positive.

13. Serum Concentration of Functional Fasinumab Over Time [Baseline, Week 2, Week 4, Week 8, Week 16]

    Summary of mean concentration of functional fasinumab are presented by nominal time point.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Clinical diagnosis of non-radicular moderate-to-severe CLBP for ≥3 months (prior to screening visit)

2. Clinical diagnosis of OA in at least 1 hip or knee joint based on the American College of Rheumatology Criteria with radiographic evidence of OA (K-L ≥2) at screening

3. History of inadequate relief of CLBP from non-pharmacologic therapy

4. Willing to undergo joint replacement (JR) surgery, if necessary

5. History of regular analgesic medication use

6. History of inadequate pain relief or intolerance to analgesics used for chronic LBP

Key Exclusion Criteria:

1. Patient is not a candidate for MRI

2. History of major trauma or back surgery in the past 6 months prior to the screening visit

3. History or presence of pyriformis syndrome

4. Evidence on baseline lumbar spine magnetic resonance imaging of potentially confounding conditions

5. History or evidence on joint imaging of conditions that may confound joint safety evaluation

6. Evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol

7. Recent use of longer acting pain medications

8. Other medical conditions that may interfere with participation or accurate assessments during the trial

Note: Other protocol defined Inclusion/ Exclusion criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regeneron Research Site	Phoenix	Arizona	United States	85053
2	Regeneron Research Site	Tucson	Arizona	United States	85704
3	Regeneron Research Site	Tucson	Arizona	United States	85712
4	Regeneron Research Site	Anaheim	California	United States	92801
5	Regeneron Research Site	Anaheim	California	United States	92805
6	Regeneron Research Site	La Mesa	California	United States	91942
7	Regeneron Research Site	North Hollywood	California	United States	91606
8	Regeneron Research Site	San Diego	California	United States	92103
9	Regeneron Research Site	San Marcos	California	United States	92078
10	Regeneron Research Site	Santa Ana	California	United States	92703
11	Regeneron Research Site	Spring Valley	California	United States	91978
12	Regeneron Research Site	Whittier	California	United States	90602
13	Regeneron Research Site	Stamford	Connecticut	United States	06905
14	Regeneron Research Site	Waterbury	Connecticut	United States	06708
15	Regeneron Research Site	Clearwater	Florida	United States	33756
16	Regeneron Research Site	Hialeah	Florida	United States	33012
17	Regeneron Research Site	Jacksonville	Florida	United States	32256
18	Regeneron Research Site	Lauderdale Lakes	Florida	United States	33319
19	Regeneron Research Site	Miami	Florida	United States	33155
20	Regeneron Research Site	Ocoee	Florida	United States	34761
21	Regeneron Research Site	Orlando	Florida	United States	32801
22	Regeneron Research Site	Orlando	Florida	United States	32806
23	Regeneron Research Site	Port Orange	Florida	United States	32127
24	Regeneron Research Site	Sarasota	Florida	United States	34232
25	Regeneron Research Site	Atlanta	Georgia	United States	30189
26	Regeneron Research Site	Columbus	Georgia	United States	31904
27	Regeneron Research Site #1	Marietta	Georgia	United States	30060
28	Regeneron Research Site #2	Marietta	Georgia	United States	30060
29	Regeneron Research Site	Newnan	Georgia	United States	30265
30	Regeneron Research Site	Idaho Falls	Idaho	United States	83404
31	Regeneron Research Site	Chicago	Illinois	United States	60602
32	Regeneron Research Site	Chicago	Illinois	United States	60607
33	Regeneron Research Site	Valparaiso	Indiana	United States	46383
34	Regeneron Research Site	West Des Moines	Iowa	United States	50265
35	Regeneron Research Site	Edgewood	Kentucky	United States	41017
36	Regeneron Research Site	New Orleans	Louisiana	United States	70115
37	Regeneron Research Site	Bay City	Michigan	United States	48706
38	Regeneron Research Site	Saint Louis	Missouri	United States	63117
39	Regeneron Research Site	Lincoln	Nebraska	United States	68516
40	Regeneron Research Site	Las Vegas	Nevada	United States	89144
41	Regeneron Research Site	Berlin	New Jersey	United States	08009
42	Regeneron Research Site	Albuquerque	New Mexico	United States	87102
43	Regeneron Research Site	Hartsdale	New York	United States	10530
44	Regeneron Research Site	New York	New York	United States	10036
45	Regeneron Research Site	High Point	North Carolina	United States	27262
46	Regeneron Research Site	Fargo	North Dakota	United States	58105
47	Regeneron Research Site	Beavercreek	Ohio	United States	45431
48	Regeneron Research Site	Oklahoma City	Oklahoma	United States	73103
49	Regeneron Research Site	Duncansville	Pennsylvania	United States	16635
50	Regeneron Research Site	Rapid City	South Dakota	United States	57702
51	Regeneron Research Site #1	Memphis	Tennessee	United States	38119
52	Regeneron Research Site #2	Memphis	Tennessee	United States	38119
53	Regeneron Research Site	Houston	Texas	United States	77058
54	Regeneron Research Site	Katy	Texas	United States	77498
55	Regeneron Research Site	Plano	Texas	United States	75075
56	Regeneron Research Site	Kenosha	Wisconsin	United States	53144

Sponsors and Collaborators

• Regeneron Pharmaceuticals
• Teva Pharmaceutical Industries, Ltd.

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jul 25, 2017
• Statistical Analysis Plan - Dec 10, 2018

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03285646
• Other Study ID Numbers: R475-PN-1612; 2017-001943-12
• First Posted: Sep 18, 2017
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Regeneron Pharmaceuticals: Knee; Hip
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Hip; Back Pain; Low Back Pain; Fasinumab

Study Results

Participant Flow

Recruitment Details	Participants were screened for study eligibility across the US. Of the 377 participants screened, 63 met eligibility criteria. The most frequently reported reason for non-randomization was inclusion criteria not met and/or exclusion criteria met (224 participants):139 did not meet inclusion criteria, 86 participants met exclusion criteria.
Pre-assignment Detail	The study consisted of a screening period of up to 30 days and a 7 (+3 day) day pre-randomization period during which all pain medication except study-provided rescue medication was discontinued.

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Period Title: Overall Study
STARTED	32	31
COMPLETED	19	27
NOT COMPLETED	13	4

Baseline Characteristics

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W	Total
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Total of all reporting groups
Overall Participants	32	31	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (9.88)	60.0 (10.52)	58.8 (10.18)
Sex: Female, Male (Count of Participants)
Female	21 65.6%	18 58.1%	39 61.9%
Male	11 34.4%	13 41.9%	24 38.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.1%	3 9.7%	4 6.3%
Not Hispanic or Latino	31 96.9%	28 90.3%	59 93.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White	15 46.9%	17 54.8%	32 50.8%
Black or African American	15 46.9%	14 45.2%	29 46%
American Indian or Alaska Native	1 3.1%	0 0%	1 1.6%
Native Hawaiian or Other Pacific Islander	1 3.1%	0 0%	1 1.6%
Average Daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS) Score (Score on a Scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a Scale]	6.66 (1.475)	6.81 (1.338)	6.73 (1.400)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score
Description	Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain.
Time Frame	Week 1, Week 2, Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Number of Participants analyzed = Participants evaluable for this endpoint

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Change from Baseline to Week 1	-0.73 (1.424)	-1.62 (2.037)
Change from Baseline to Week 2	-0.98 (1.588)	-2.15 (2.067)
Change from Baseline to Week 4	-1.28 (1.878)	-2.64 (2.038)
Change from Baseline to Week 8	-1.21 (1.568)	-2.82 (1.963)
Change from Baseline to Week 12	-2.12 (1.582)	-3.18 (2.046)
Change from Baseline to Week 16	-0.77 (1.943)	-2.32 (1.367)

2. Secondary Outcome

Title	Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score
Description	The RMDQ is a self-administered, health status measure for lower back pain (LBP). It measures pain and function using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores are indicative of better function.
Time Frame	Week 2, Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed = Participants evaluable for this endpoint

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Change from Baseline to Week 2	-2.70 (5.120)	-2.54 (4.836)
Change from Baseline to Week 4	-1.92 (4.529)	-3.09 (3.884)
Change from Baseline to Week 8	0.37 (4.487)	-4.18 (5.015)
Change from Baseline to Week 12	0.83 (3.061)	-3.33 (4.301)
Change from Baseline to Week 16	-1.00 (NA)	-5.75 (3.948)

3. Secondary Outcome

Title	Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score
Description	The PGA of LBP is a participant assessed 5 point Likert scale of LBP ranging from 1-5 where 1 = very well; 2 = well; 3 = fair; 4 = poor; and 5 = very poor.
Time Frame	Week 2, Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed = Participants evaluable for this endpoint

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Change from Baseline to Week 2	-0.44 (0.751)	-0.76 (0.786)
Change from Baseline to Week 4	-0.60 (0.957)	-1.04 (0.676)
Change from Baseline to Week 8	-0.55 (0.945)	-1.10 (1.021)
Change from Baseline to Week 12	-0.57 (1.134)	-1.00 (1.333)
Change from Baseline to Week 16	0.00 (NA)	-0.75 (0.500)

4. Secondary Outcome

Title	Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score
Description	Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Count of Participants [Participants]	12 37.5%	21 67.7%

5. Secondary Outcome

Title	Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score
Description	The BPI-sf is a self-administered questionnaire for participants to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function. With a recall period of 24 hours, the questionnaire contains the front and back body diagrams, the 4 pain severity items and 7 pain interference items rated on 0-10 scale; total interference score ranges from 0-10 (0, does not interfere; 10 completely interferes), and the question about percentage of pain relief by analgesics. The BPI pain interference is typically scored as the mean of the 7 interference items.
Time Frame	Week 2, Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed = Participants evaluable for this endpoint

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Change from Baseline to Week 2	-1.55 (2.306)	-1.94 (2.255)
Change from Baseline to Week 4	-1.49 (2.390)	-2.15 (2.157)
Change from Baseline to Week 8	-1.31 (2.119)	-2.70 (2.774)
Change from Baseline to Week 12	-1.63 (2.096)	-1.84 (1.978)
Change from Baseline to Week 16	-1.14 (NA)	-1.29 (3.017)

6. Secondary Outcome

Title	Number of Adjudicated Arthropathy (AA) Events
Description	Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Adjudicated Arthropathy (AA) Events]	0	2

7. Secondary Outcome

Title	Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria
Description	Destructive arthropathy (DA) is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive Osteoarthritis type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Destructive Arthropathy (DA) Events]	0	0

8. Secondary Outcome

Title	Number of Treatment-Emergent Adverse Events (TEAEs)
Description	Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Treatment-Emergent Adverse Events]	33	14

9. Secondary Outcome

Title	Number of Sympathetic Nervous System (SNS) Dysfunction Events
Description	Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Sympathetic NS Dysfunction Events]	0	0

10. Secondary Outcome

Title	Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation
Description	Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Hypoaesthesia events	1	0
Paraesthesia events	1	0

11. Secondary Outcome

Title	Number of All-Cause Joint Replacement (JR) Surgery Events
Description	All joint replacement surgery events regardless of cause.
Time Frame	Up to Week 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Joint Replacement (JR) Surgery Events]	2	1

12. Secondary Outcome

Title	Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug
Description	An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (week 12) to evaluate the number of participants who had undergone or were scheduled for JR surgery.
Time Frame	Up to Week 64

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	32	31
Number [Joint Replacement (JR) Surgery Events]	0	0

13. Secondary Outcome

Title	Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay
Description	Samples for Anti-Drug Antibody (ADA) evaluation were collected at baseline and at subsequent study visits. ADA variables include ADA status (+ or -) and titer as follows: Total participants negative in the ADA assay at all time points analyzed. Pre-existing immunoreactivity - positive response at baseline with all post-dose results negative, or a positive response at baseline with all post-dose responses less than 9-fold over baseline titer levels. Treatment emergent - post-dose positive result when baseline results were negative. Persistent - A positive result detected in at least 2 consecutive post baseline samples separated by at least a 16-week post baseline period, with no negative results in-between. Indeterminate - A positive result at the last collection time point analyzed only. Transient - Not persistent or indeterminate regardless of any missing samples. Treatment boosted - any post-dose positive result at least 9-fold over the baseline level when baseline is positive.
Time Frame	16 Weeks

Outcome Measure Data

Analysis Population Description

Anti-Drug Antibody (ADA) analysis set: All treated participants who received any study drug or placebo (safety analysis set) and had at least one non-missing anti-drug antibody result following the first dose of study drug or placebo

Arm/Group Title	Fasinumab-matching Placebo	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	31	31
Negative/Pre-Existing	31 96.9%	31 100%
Treatment Boosted	0 0%	0 0%
Treatment-Emergent	0 0%	0 0%
Treatment-Emergent: Persistent	0 0%	0 0%
Treatment-Emergent: Transient	0 0%	0 0%
Treatment-Emergent: Indeterminate	0 0%	0 0%

14. Secondary Outcome

Title	Serum Concentration of Functional Fasinumab Over Time
Description	Summary of mean concentration of functional fasinumab are presented by nominal time point.
Time Frame	Baseline, Week 2, Week 4, Week 8, Week 16

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed = Participants evaluable for this endpoint

Arm/Group Title	Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
Measure Participants	31
Baseline	0 (0)
Week 2	0.262 (0.0992)
Week 4	0.176 (0.0679)
Week 8	0.247 (0.130)
Week 16	0.192 (0.0932)

Adverse Events

Time Frame	From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36)
Adverse Event Reporting Description	Reported adverse events (AEs) are AEs that developed/worsened from the time of the first administration of study drug until the end of the follow up period (week 36)
Arm/Group Title	Fasinumab-matching Placebo		Fasinumab 3 mg SC Q4W
Arm/Group Description	Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.		Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks.
All Cause Mortality
	Fasinumab-matching Placebo		Fasinumab 3 mg SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/31 (0%)
Serious Adverse Events
	Fasinumab-matching Placebo		Fasinumab 3 mg SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		2/31 (6.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/32 (3.1%)	2	0/31 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer stage IV	0/32 (0%)	0	1/31 (3.2%)	1
Nervous system disorders
Dizziness	0/32 (0%)	0	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/32 (0%)	0	1/31 (3.2%)	1
Other (Not Including Serious) Adverse Events
	Fasinumab-matching Placebo		Fasinumab 3 mg SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/32 (43.8%)		4/31 (12.9%)
General disorders
Peripheral swelling	2/32 (6.3%)	2	0/31 (0%)	0
Infections and infestations
Upper respiratory tract infection	4/32 (12.5%)	4	1/31 (3.2%)	1
Investigations
Blood creatine phosphokinase increased	3/32 (9.4%)	3	1/31 (3.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	4/32 (12.5%)	7	3/31 (9.7%)	4
Back pain	5/32 (15.6%)	5	0/31 (0%)	0
Neck Pain	2/32 (6.3%)	2	1/31 (3.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/32 (6.3%)	2	0/31 (0%)	0

Limitations/Caveats

Enrollment and study drug administration was stopped due to an urgent safety measure. As a result the small number of participants enrolled in this study limited the interpretability of the efficacy results.

More Information

Certain Agreements

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

The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.