Trial Outcomes & Findings for Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee (NCT NCT03285646)

NCT ID: NCT03285646

Last Updated: 2021-06-30

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 63 participants
• Primary outcome timeframe: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
• Results posted on: 2021-06-30

Participant Flow

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.

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.

Participant milestones

Measure	Fasinumab-matching Placebo 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.	Fasinumab 3 mg SC Q4W 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.
Overall Study STARTED	32	31
Overall Study COMPLETED	19	27
Overall Study NOT COMPLETED	13	4

Reasons for withdrawal

Measure	Fasinumab-matching Placebo 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.	Fasinumab 3 mg SC Q4W 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.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	10	2
Overall Study Lost to Follow-up	2	1
Overall Study Investigator/Sponsor Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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 n=63 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 9.88 • n=5 Participants	60.0 years STANDARD_DEVIATION 10.52 • n=7 Participants	58.8 years STANDARD_DEVIATION 10.18 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	18 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Average Daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS) Score	6.66 Score on a Scale STANDARD_DEVIATION 1.475 • n=5 Participants	6.81 Score on a Scale STANDARD_DEVIATION 1.338 • n=7 Participants	6.73 Score on a Scale STANDARD_DEVIATION 1.400 • n=5 Participants

PRIMARY outcome

Timeframe: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16

Population: Number of Participants analyzed = Participants evaluable for this endpoint

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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 1	-0.73 Score on a Scale Standard Deviation 1.424	-1.62 Score on a Scale Standard Deviation 2.037
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 2	-0.98 Score on a Scale Standard Deviation 1.588	-2.15 Score on a Scale Standard Deviation 2.067
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 4	-1.28 Score on a Scale Standard Deviation 1.878	-2.64 Score on a Scale Standard Deviation 2.038
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 8	-1.21 Score on a Scale Standard Deviation 1.568	-2.82 Score on a Scale Standard Deviation 1.963
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 12	-2.12 Score on a Scale Standard Deviation 1.582	-3.18 Score on a Scale Standard Deviation 2.046
Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score Change from Baseline to Week 16	-0.77 Score on a Scale Standard Deviation 1.943	-2.32 Score on a Scale Standard Deviation 1.367

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 8, Week 12, Week 16

Population: Number of Participants Analyzed = Participants evaluable for this endpoint

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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score Change from Baseline to Week 2	-2.70 Score on a Scale Standard Deviation 5.120	-2.54 Score on a Scale Standard Deviation 4.836
Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score Change from Baseline to Week 4	-1.92 Score on a Scale Standard Deviation 4.529	-3.09 Score on a Scale Standard Deviation 3.884
Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score Change from Baseline to Week 8	0.37 Score on a Scale Standard Deviation 4.487	-4.18 Score on a Scale Standard Deviation 5.015
Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score Change from Baseline to Week 12	0.83 Score on a Scale Standard Deviation 3.061	-3.33 Score on a Scale Standard Deviation 4.301
Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score Change from Baseline to Week 16	-1.00 Score on a Scale Standard Deviation NA Standard deviation could not be calculated due to insufficient number of participants	-5.75 Score on a Scale Standard Deviation 3.948

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 8, Week 12, Week 16

Population: Number of Participants Analyzed = Participants evaluable for this endpoint

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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score Change from Baseline to Week 2	-0.44 Score on a Scale Standard Deviation 0.751	-0.76 Score on a Scale Standard Deviation 0.786
Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score Change from Baseline to Week 4	-0.60 Score on a Scale Standard Deviation 0.957	-1.04 Score on a Scale Standard Deviation 0.676
Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score Change from Baseline to Week 8	-0.55 Score on a Scale Standard Deviation 0.945	-1.10 Score on a Scale Standard Deviation 1.021
Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score Change from Baseline to Week 12	-0.57 Score on a Scale Standard Deviation 1.134	-1.00 Score on a Scale Standard Deviation 1.333
Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score Change from Baseline to Week 16	0.00 Score on a Scale Standard Deviation NA Standard deviation could not be calculated due to insufficient number of participants	-0.75 Score on a Scale Standard Deviation 0.500

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score	12 Participants	21 Participants

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 8, Week 12, Week 16

Population: Number of Participants Analyzed = Participants evaluable for this endpoint

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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score Change from Baseline to Week 2	-1.55 Score on a Scale Standard Deviation 2.306	-1.94 Score on a Scale Standard Deviation 2.255
Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score Change from Baseline to Week 4	-1.49 Score on a Scale Standard Deviation 2.390	-2.15 Score on a Scale Standard Deviation 2.157
Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score Change from Baseline to Week 8	-1.31 Score on a Scale Standard Deviation 2.119	-2.70 Score on a Scale Standard Deviation 2.774
Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score Change from Baseline to Week 12	-1.63 Score on a Scale Standard Deviation 2.096	-1.84 Score on a Scale Standard Deviation 1.978
Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score Change from Baseline to Week 16	-1.14 Score on a Scale Standard Deviation NA Standard deviation could not be calculated due to insufficient number of participants	-1.29 Score on a Scale Standard Deviation 3.017

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Adjudicated Arthropathy (AA) Events	0 Adjudicated Arthropathy (AA) Events	2 Adjudicated Arthropathy (AA) Events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria	0 Destructive Arthropathy (DA) Events	0 Destructive Arthropathy (DA) Events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Treatment-Emergent Adverse Events (TEAEs)	33 Treatment-Emergent Adverse Events	14 Treatment-Emergent Adverse Events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Sympathetic Nervous System (SNS) Dysfunction Events	0 Sympathetic NS Dysfunction Events	0 Sympathetic NS Dysfunction Events

SECONDARY outcome

Timeframe: Up to Week 36

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

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation Hypoaesthesia events	1 Peripheral Sensory Adverse Events (AEs)	0 Peripheral Sensory Adverse Events (AEs)
Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation Paraesthesia events	1 Peripheral Sensory Adverse Events (AEs)	0 Peripheral Sensory Adverse Events (AEs)

SECONDARY outcome

Timeframe: Up to Week 36

All joint replacement surgery events regardless of cause.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of All-Cause Joint Replacement (JR) Surgery Events	2 Joint Replacement (JR) Surgery Events	1 Joint Replacement (JR) Surgery Events

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Fasinumab-matching Placebo n=32 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug	0 Joint Replacement (JR) Surgery Events	0 Joint Replacement (JR) Surgery Events

SECONDARY outcome

Timeframe: 16 Weeks

Population: 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

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.

Outcome measures

Measure	Fasinumab-matching Placebo n=31 Participants 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.	Fasinumab 3 mg SC Q4W n=31 Participants 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.
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Negative/Pre-Existing	31 Participants	31 Participants
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Treatment Boosted	0 Participants	0 Participants
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Treatment-Emergent	0 Participants	0 Participants
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Treatment-Emergent: Persistent	0 Participants	0 Participants
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Treatment-Emergent: Transient	0 Participants	0 Participants
Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay Treatment-Emergent: Indeterminate	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 8, Week 16

Population: Number of Participants Analyzed = Participants evaluable for this endpoint

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

Outcome measures

Measure	Fasinumab-matching Placebo n=31 Participants 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.	Fasinumab 3 mg SC Q4W 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.
Serum Concentration of Functional Fasinumab Over Time Baseline	0 Milligram per Liter (mg/L) Standard Deviation 0	—
Serum Concentration of Functional Fasinumab Over Time Week 2	0.262 Milligram per Liter (mg/L) Standard Deviation 0.0992	—
Serum Concentration of Functional Fasinumab Over Time Week 4	0.176 Milligram per Liter (mg/L) Standard Deviation 0.0679	—
Serum Concentration of Functional Fasinumab Over Time Week 8	0.247 Milligram per Liter (mg/L) Standard Deviation 0.130	—
Serum Concentration of Functional Fasinumab Over Time Week 16	0.192 Milligram per Liter (mg/L) Standard Deviation 0.0932	—

Adverse Events

Fasinumab-matching Placebo

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Fasinumab 3 mg SC Q4W

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fasinumab-matching Placebo n=32 participants at risk 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.	Fasinumab 3 mg SC Q4W n=31 participants at risk 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage IV	0.00% 0/32 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Nervous system disorders Dizziness	0.00% 0/32 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/32 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Musculoskeletal and connective tissue disorders Osteoarthritis	3.1% 1/32 • Number of events 2 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	0.00% 0/31 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)

Other adverse events

Measure	Fasinumab-matching Placebo n=32 participants at risk 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.	Fasinumab 3 mg SC Q4W n=31 participants at risk 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.
Infections and infestations Upper respiratory tract infection	12.5% 4/32 • Number of events 4 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 4/32 • Number of events 7 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	9.7% 3/31 • Number of events 4 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Investigations Blood creatine phosphokinase increased	9.4% 3/32 • Number of events 3 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Musculoskeletal and connective tissue disorders Back pain	15.6% 5/32 • Number of events 5 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	0.00% 0/31 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Musculoskeletal and connective tissue disorders Neck Pain	6.2% 2/32 • Number of events 2 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	3.2% 1/31 • Number of events 1 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
General disorders Peripheral swelling	6.2% 2/32 • Number of events 2 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	0.00% 0/31 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)
Respiratory, thoracic and mediastinal disorders Cough	6.2% 2/32 • Number of events 2 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)	0.00% 0/31 • From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36) 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)

Additional Information

Study Director

Regeneron Pharmaceuticals, Inc.

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER