A Study to Determine the Efficacy and Safety of Fasinumab for the Treatment of Adults With Chronic Low Back Pain

• Sponsor: Regeneron Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02620020
• Collaborator: (none)
• Enrollment: 563
• Locations: 74
• Arms: 4
• Actual Duration (Months): 19.6
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The main objective of the trial is to evaluate the efficacy of fasinumab compared to placebo as measured by the change from baseline in the average daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS).

Secondary objectives of the study are to evaluate the efficacy of fasinumab compared to placebo as measured by:

• Change from baseline in the Roland Morris disability questionnaire (RMDQ) total score

• Change from baseline in the Patient Global Assessment (PGA) of Low Back Pain (LBP) score

• Change from baseline in the average daily LBPI NRS score

Condition or Disease	Intervention/Treatment	Phase
Low Back Pain	Drug: Fasinumab; Drug: placebo	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 563 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Multi-dose, Placebo-controlled Phase 2/3 Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate to Severe Chronic Low Back Pain
• Actual Study Start Date: Jan 26, 2016
• Actual Primary Completion Date: Feb 3, 2017
• Actual Study Completion Date: Sep 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fasinumab 6 mg SC Q4W and Placebo IV Q8W Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Drug: Fasinumab; Participants received fasinumab SC or IV, Q4W or Q8W.; Other Names: REGN475 ; Drug: placebo; Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.
Experimental: Fasinumab 9 mg SC Q4W and Placebo IV Q8W Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Drug: Fasinumab; Participants received fasinumab SC or IV, Q4W or Q8W.; Other Names: REGN475 ; Drug: placebo; Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.
Experimental: Fasinumab 9 mg IV Q8W and Placebo SC Q4W Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.	Drug: Fasinumab; Participants received fasinumab SC or IV, Q4W or Q8W.; Other Names: REGN475 ; Drug: placebo; Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.
Experimental: Placebo SC Q4W and Placebo IV Q8W Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Drug: placebo; Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.

Outcome Measures

Primary Outcome Measures

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

   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.

2. Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score [Baseline to Week 16]

   The RMDQ is a self-administered, widely used 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 - that is from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores indicative of better function.

3. Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score [Baseline to Week 16]

   The PGA of LBP is a participant assessed 5 point Likert scale of LBP ranging from 0-5 where 1=very well; 2=well; 3=fair; 4=poor; and 5=very poor.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Male or female ≥35 years of age at the screening visit

2. Clinical diagnosis of chronic moderate to severe LBP (nonradiculopathic)for ≥3 months

3. History of regular analgesic medication

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

5. Willing to discontinue current pain medication

Key Exclusion Criteria:

1. History of lumbosacral radiculopathy within the past 2 years

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

3. Recent use of longer acting pain medications

4. Evidence of destructive arthropathy

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Chandler	Arizona	United States
3		Glendale	Arizona	United States
4		Mesa	Arizona	United States
5		Phoenix	Arizona	United States
6		Scottsdale	Arizona	United States
7		Tucson	Arizona	United States
8		Little Rock	Arkansas	United States
9		Beverly Hills	California	United States
10		Carlsbad	California	United States
11		Lakewood	California	United States
12		Long Beach	California	United States
13		Sacramento	California	United States
14		San Diego	California	United States
15		Santa Rosa	California	United States
16		Vista	California	United States
17		Aurora	Colorado	United States
18		Colorado Springs	Colorado	United States
19		Littleton	Colorado	United States
20		Washington	District of Columbia	United States
21		Clearwater	Florida	United States
22		Fort Myers	Florida	United States
23		Leesburg	Florida	United States
24		Miami	Florida	United States
25		Orlando	Florida	United States
26		Chicago	Illinois	United States
27		Evansville	Indiana	United States
28		Council Bluffs	Iowa	United States
29		Worcester	Massachusetts	United States
30		Edina	Minnesota	United States
31		Kansas City	Missouri	United States
32		Saint Louis	Missouri	United States
33		Elkhorn	Nebraska	United States
34		Henderson	Nevada	United States
35		Las Vegas	Nevada	United States
36		Jamaica	New York	United States
37		New York	New York	United States
38		Williamsville	New York	United States
39		Cary	North Carolina	United States
40		High Point	North Carolina	United States
41		Raleigh	North Carolina	United States
42		Salisbury	North Carolina	United States
43		Wilmington	North Carolina	United States
44		Akron	Ohio	United States
45		Cincinnati	Ohio	United States
46		Columbus	Ohio	United States
47		Oklahoma City	Oklahoma	United States
48		Duncansville	Pennsylvania	United States
49		Anderson	South Carolina	United States
50		Greer	South Carolina	United States
51		Bristol	Tennessee	United States
52		Knoxville	Tennessee	United States
53		Cypress	Texas	United States
54		Dallas	Texas	United States
55		Lubbock	Texas	United States
56		Plano	Texas	United States
57		San Antonio	Texas	United States
58		Salt Lake City	Utah	United States
59		London	Ontario	Canada
60		Toronto	Ontario	Canada
61		Prague		Czechia
62		Rychnov Nad Kneznou		Czechia
63		Aalborg		Denmark
64		Ballerup		Denmark
65		Tallinn		Estonia
66		Budapest		Hungary
67		Gyula		Hungary
68		Szolnok		Hungary
69		Bialystok		Poland
70		Lodz		Poland
71		Lublin		Poland
72		Rzeszow		Poland
73		Warszawa		Poland
74		Zgierz		Poland

Sponsors and Collaborators

• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 26, 2016
• Statistical Analysis Plan - Mar 20, 2017

More Information

Publications

None provided.

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02620020
• Other Study ID Numbers: R475-PN-1524; 2015-003782-28
• First Posted: Dec 2, 2015
• Last Update Posted: Jun 16, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Back Pain; Low Back Pain; Fasinumab

Study Results

Participant Flow

Recruitment Details	The study was conducted at 105 sites in US, CA & EU from 26Jan2016 - 13Sep2017. Of 1,783 participants screened, 563 randomized to 1 of 4 groups stratified by baseline low back pain numerical rating scale (LBP NRS) score (<7, ≥7), duration of chronic LBP (<5, ≥5yrs) & max. Kellgren-Lawrence (K-L) score (≤2, >2) at any knee/ hip joint at screening.
Pre-assignment Detail	The study consisted of a screening period of up to 30 days & a 7-day pre-randomization period during which pain medication, except study-provided rescue medication, was discontinued. Confirmation of no exclusionary findings on joint on which imaging was performed during screening must have been received before a participant could be randomized.

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.
Period Title: Overall Study
STARTED	141	141	140	141
Modified Intent to Treat Set (mITT)	140	139	139	140
COMPLETED	97	106	115	115
NOT COMPLETED	44	35	25	26

Baseline Characteristics

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W	Total
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.	Total of all reporting groups
Overall Participants	141	141	140	141	563
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (12.54)	58.2 (11.29)	56.6 (10.99)	55.4 (10.49)	57.1 (11.38)
Age, Customized (Number) [Number]
< 65 years	93 66%	95 67.4%	109 77.9%	117 83%	414 73.5%
≥ 65 years	48 34%	46 32.6%	31 22.1%	24 17%	149 26.5%
Sex: Female, Male (Count of Participants)
Female	83 58.9%	85 60.3%	84 60%	81 57.4%	333 59.1%
Male	58 41.1%	56 39.7%	56 40%	60 42.6%	230 40.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 5%	4 2.8%	4 2.9%	10 7.1%	25 4.4%
Not Hispanic or Latino	134 95%	135 95.7%	135 96.4%	131 92.9%	535 95%
Unknown or Not Reported	0 0%	2 1.4%	1 0.7%	0 0%	3 0.5%
Race/Ethnicity, Customized (Number) [Number]
White	127 90.1%	119 84.4%	118 84.3%	116 82.3%	480 85.3%
Black or African American	13 9.2%	19 13.5%	19 13.6%	21 14.9%	72 12.8%
Asian	1 0.7%	2 1.4%	2 1.4%	1 0.7%	6 1.1%
American Indian or Alaska Native	0 0%	1 0.7%	0 0%	1 0.7%	2 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 0.7%	1 0.2%
Other	0 0%	0 0%	1 0.7%	1 0.7%	2 0.4%
Low Back Pain Intensity Numerical Rating Scale (LBPI NRS) Baseline Score (Scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Scores on a scale]	6.50 (1.297)	6.49 (1.2481)	6.66 (1.300)	6.45 (1.191)	6.53 (1.267)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (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	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Analysis performed on modified intent to treat set (mITT) included all randomized participants who received at least one dose of study drug based on the treatment allocated (as randomized) including data up to 5 weeks after the last dose of study drug. Number of participants analyzed = participants with available data for specified time point.

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.
Measure Participants	140	139	139	140
Least Squares Mean (Standard Error) [Scores on a scale]	-1.7 (0.23)	-2.0 (0.23)	-2.5 (0.22)	-2.4 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 6 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3876
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.88 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.31
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0180
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.32 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0288
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.26 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS)
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	Baseline to Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Analysis performed on modified intent to treat set (mITT) included all randomized participants who received at least one dose of study drug based on the treatment allocated (as randomized) including data up to 5 weeks after the last dose of study drug. Number of participants analyzed = participants with available data for specified time point.

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.
Measure Participants	140	139	139	140
Change from Baseline to Week 2	-0.9 (0.17)	-1.3 (0.17)	-1.6 (0.17)	-1.6 (0.16)
Change from Baseline to Week 4	-0.9 (0.17)	-1.5 (0.17)	-2.0 (0.17)	-1.9 (0.16)
Change from Baseline to Week 8	-1.2 (0.19)	-1.8 (0.19)	-2.3 (0.19)	-2.2 (0.19)
Change from Baseline to Week 12	-1.5 (0.21)	-2.0 (0.21)	-2.6 (0.21)	-2.5 (0.21)

3. Secondary Outcome

Title	Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score
Description	The RMDQ is a self-administered, widely used 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 - that is from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores indicative of better function.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, number of participants analyzed = participants with available data for specified time point.

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.
Measure Participants	46	46	55	55
Least Squares Mean (Standard Error) [Units on a scale]	-3.8 (0.54)	-6.0 (0.54)	-5.8 (0.51)	-6.3 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 6 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -3.65 to -0.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2
	Confidence Interval	(2-Sided) 95%; -3.36 to -0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.72
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -3.88 to -1.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.72
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 16 in the 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 0-5 where 1=very well; 2=well; 3=fair; 4=poor; and 5=very poor.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, number of participants analyzed=participants with available data for specified time point.

Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W	Fasinumab 6 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg SC Q4W and Placebo IV Q8W	Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8.	Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12.
Measure Participants	50	48	55	57
Least Squares Mean (Standard Error) [Units on a scale]	-0.7 (0.10)	-0.9 (0.10)	-0.8 (0.10)	-1.0 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 6 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1501
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.46 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg SC Q4W and Placebo IV Q8W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2603
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo SC Q4W and Placebo IV Q8W, Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0135
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.59 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Safety analysis set (SAF): All randomized participants who received any study drug (based on treatment received [as treated]). Reported AEs & deaths are treatment emergent: AEs that developed/worsened & deaths that occurred during 'treatment emergent period' (from 1st dose of study drug up to 4 wks after last dose of SC drug, or 8 wks after last dose of IV study drug, whichever is later). Reported death occurred during post-treatment follow-up period in fasinumab 6 mg SC Q4W & placebo IV Q8W arm
Arm/Group Title	Placebo SC Q4W and Placebo IV Q8W		Fasinumab 6 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg IV Q8W and Placebo SC Q4W
Arm/Group Description	Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8. Patients randomized to the 'Placebo SC Q4W and Placebo IV Q8W" treatment arm who wrongly received at least one dose of active treatment were classified in the active treatment group in the SAF.		Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8. Participants randomized to any of the active treatment groups receiving active fasinumab doses who wrongly received another dose of fasinumab were classified to the arm of the lowest dose of fasinumab received. For example, a participant randomized to the 'fasinumab 9 mg SC Q4W and placebo 9 mg IV Q8W' who wrongly received treatment with fasinumab 6 mg SC at least once was classified under the 'fasinumab 6 mg SC Q4W and placebo IV Q8W' treatment arm.		Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8. Participants randomized to any of the active treatment groups receiving active fasinumab doses who wrongly received another dose of fasinumab were classified to the arm of the lowest dose of fasinumab received. For example, a participant randomized to the 'fasinumab 9 mg SC Q4W and placebo 9 mg IV Q8W' who wrongly received treatment with fasinumab 6 mg SC at least once was classified under the 'fasinumab 6 mg SC Q4W and placebo IV Q8W' treatment arm.		Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12. Participants randomized to any of the active treatment groups receiving active fasinumab doses who wrongly received another dose of fasinumab were classified to the arm of the lowest dose of fasinumab received. For example, a participant randomized to the 'fasinumab 9 mg SC Q4W and placebo 9 mg IV Q8W' who wrongly received treatment with fasinumab 6 mg SC at least once was classified under the 'fasinumab 6 mg SC Q4W and placebo IV Q8W' treatment arm.
All Cause Mortality
	Placebo SC Q4W and Placebo IV Q8W		Fasinumab 6 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/140 (0%)		1/139 (0.7%)		0/139 (0%)		0/140 (0%)
Serious Adverse Events
	Placebo SC Q4W and Placebo IV Q8W		Fasinumab 6 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/140 (2.9%)		2/139 (1.4%)		3/139 (2.2%)		5/140 (3.6%)
Cardiac disorders
Angina pectoris	0/140 (0%)	0	1/139 (0.7%)	1	0/139 (0%)	0	0/140 (0%)	0
General disorders
Pyrexia	0/140 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	1/140 (0.7%)	1
Infections and infestations
Diverticulitis	0/140 (0%)	0	0/139 (0%)	0	1/139 (0.7%)	1	0/140 (0%)	0
Injury, poisoning and procedural complications
Concussion	0/140 (0%)	0	1/139 (0.7%)	1	0/139 (0%)	0	0/140 (0%)	0
Craniocerebral injury	0/140 (0%)	0	1/139 (0.7%)	1	0/139 (0%)	0	0/140 (0%)	0
Eye injury	1/140 (0.7%)	1	0/139 (0%)	0	0/139 (0%)	0	0/140 (0%)	0
Meniscus injury	0/140 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	1/140 (0.7%)	1
Patella fracture	0/140 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	1/140 (0.7%)	1
Skull fracture	0/140 (0%)	0	1/139 (0.7%)	1	0/139 (0%)	0	0/140 (0%)	0
Investigations
Blood creatine phosphokinase increased	1/140 (0.7%)	1	0/139 (0%)	0	0/139 (0%)	0	0/140 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/140 (0%)	0	0/139 (0%)	0	1/139 (0.7%)	1	0/140 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/140 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	1/140 (0.7%)	1
Tongue carcinoma stage IV	1/140 (0.7%)	1	0/139 (0%)	0	0/139 (0%)	0	0/140 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/140 (0.7%)	1	0/139 (0%)	0	0/139 (0%)	0	0/140 (0%)	0
Haemorrhagic stroke	0/140 (0%)	0	0/139 (0%)	0	1/139 (0.7%)	1	0/140 (0%)	0
Vascular disorders
Hypotension	0/140 (0%)	0	0/139 (0%)	0	0/139 (0%)	0	1/140 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Placebo SC Q4W and Placebo IV Q8W		Fasinumab 6 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg SC Q4W and Placebo IV Q8W		Fasinumab 9 mg IV Q8W and Placebo SC Q4W
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/140 (31.4%)		35/139 (25.2%)		52/139 (37.4%)		49/140 (35%)
Gastrointestinal disorders
Nausea	2/140 (1.4%)	4	4/139 (2.9%)	4	7/139 (5%)	7	1/140 (0.7%)	1
Infections and infestations
Nasopharyngitis	8/140 (5.7%)	8	9/139 (6.5%)	9	8/139 (5.8%)	9	10/140 (7.1%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	17/140 (12.1%)	22	15/139 (10.8%)	26	16/139 (11.5%)	24	21/140 (15%)	26
Back pain	7/140 (5%)	7	0/139 (0%)	0	4/139 (2.9%)	4	5/140 (3.6%)	5
Pain in extremity	12/140 (8.6%)	14	3/139 (2.2%)	4	5/139 (3.6%)	5	4/140 (2.9%)	7
Nervous system disorders
Headache	9/140 (6.4%)	11	9/139 (6.5%)	9	9/139 (6.5%)	19	9/140 (6.4%)	9
Hypoaesthesia	4/140 (2.9%)	4	4/139 (2.9%)	4	7/139 (5%)	7	3/140 (2.1%)	3
Paraesthesia	4/140 (2.9%)	5	6/139 (4.3%)	6	9/139 (6.5%)	10	9/140 (6.4%)	9

Limitations/Caveats

FDA placed study on partial clinical hold. Sponsor did not amend the protocol and enrollment and dosing were not resumed. However randomized participants completed all remaining study visits/procedures per protocol except for dosing.

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.