Trial Outcomes & Findings for A Study to Determine the Efficacy and Safety of Fasinumab for the Treatment of Adults With Chronic Low Back Pain (NCT NCT02620020)

NCT ID: NCT02620020

Last Updated: 2020-06-16

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

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

563 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2020-06-16

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.	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.
Overall Study STARTED	141	141	140	141
Overall Study Modified Intent to Treat Set (mITT)	140	139	139	140
Overall Study COMPLETED	97	106	115	115
Overall Study NOT COMPLETED	44	35	25	26

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.	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.
Overall Study Adverse Event	8	4	3	5
Overall Study Lost to Follow-up	4	8	1	4
Overall Study Physician Decision	7	4	3	4
Overall Study Protocol Violation	5	2	1	1
Overall Study Withdrawal by Subject	20	16	17	12
Overall Study Death	0	1	0	0

Baseline Characteristics

Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo SC Q4W and Placebo IV Q8W n=141 Participants 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=141 Participants 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=140 Participants 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=141 Participants 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 n=563 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 12.54 • n=141 Participants	58.2 years STANDARD_DEVIATION 11.29 • n=141 Participants	56.6 years STANDARD_DEVIATION 10.99 • n=140 Participants	55.4 years STANDARD_DEVIATION 10.49 • n=141 Participants	57.1 years STANDARD_DEVIATION 11.38 • n=563 Participants
Age, Customized < 65 years	93 Participants n=141 Participants	95 Participants n=141 Participants	109 Participants n=140 Participants	117 Participants n=141 Participants	414 Participants n=563 Participants
Age, Customized ≥ 65 years	48 Participants n=141 Participants	46 Participants n=141 Participants	31 Participants n=140 Participants	24 Participants n=141 Participants	149 Participants n=563 Participants
Sex: Female, Male Female	83 Participants n=141 Participants	85 Participants n=141 Participants	84 Participants n=140 Participants	81 Participants n=141 Participants	333 Participants n=563 Participants
Sex: Female, Male Male	58 Participants n=141 Participants	56 Participants n=141 Participants	56 Participants n=140 Participants	60 Participants n=141 Participants	230 Participants n=563 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=141 Participants	4 Participants n=141 Participants	4 Participants n=140 Participants	10 Participants n=141 Participants	25 Participants n=563 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=141 Participants	135 Participants n=141 Participants	135 Participants n=140 Participants	131 Participants n=141 Participants	535 Participants n=563 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=141 Participants	2 Participants n=141 Participants	1 Participants n=140 Participants	0 Participants n=141 Participants	3 Participants n=563 Participants
Race/Ethnicity, Customized White	127 Participants n=141 Participants	119 Participants n=141 Participants	118 Participants n=140 Participants	116 Participants n=141 Participants	480 Participants n=563 Participants
Race/Ethnicity, Customized Black or African American	13 Participants n=141 Participants	19 Participants n=141 Participants	19 Participants n=140 Participants	21 Participants n=141 Participants	72 Participants n=563 Participants
Race/Ethnicity, Customized Asian	1 Participants n=141 Participants	2 Participants n=141 Participants	2 Participants n=140 Participants	1 Participants n=141 Participants	6 Participants n=563 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=141 Participants	1 Participants n=141 Participants	0 Participants n=140 Participants	1 Participants n=141 Participants	2 Participants n=563 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=141 Participants	0 Participants n=141 Participants	0 Participants n=140 Participants	1 Participants n=141 Participants	1 Participants n=563 Participants
Race/Ethnicity, Customized Other	0 Participants n=141 Participants	0 Participants n=141 Participants	1 Participants n=140 Participants	1 Participants n=141 Participants	2 Participants n=563 Participants
Low Back Pain Intensity Numerical Rating Scale (LBPI NRS) Baseline Score	6.50 Scores on a scale STANDARD_DEVIATION 1.297 • n=140 Participants • Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.	6.49 Scores on a scale STANDARD_DEVIATION 1.2481 • n=139 Participants • Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.	6.66 Scores on a scale STANDARD_DEVIATION 1.300 • n=140 Participants • Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.	6.45 Scores on a scale STANDARD_DEVIATION 1.191 • n=141 Participants • Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.	6.53 Scores on a scale STANDARD_DEVIATION 1.267 • n=560 Participants • Full analysis set (FAS): included all randomized patients per IVRS and was based on the treatment allocated (as randomized). Baseline number analyzed = number of participants in FAS; number analyzed here = number of participants within a specified category. EDiary NRS data were missing for some participants at Baseline.

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo SC Q4W and Placebo IV Q8W n=140 Participants 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=139 Participants 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=139 Participants 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=140 Participants 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.
Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score	-1.7 Scores on a scale Standard Error 0.23	-2.0 Scores on a scale Standard Error 0.23	-2.5 Scores on a scale Standard Error 0.22	-2.4 Scores on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline to Weeks 2, 4, 8, and 12

Outcome measures

Outcome measures
Measure	Placebo SC Q4W and Placebo IV Q8W n=140 Participants 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=139 Participants 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=139 Participants 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=140 Participants 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.
Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) Change from Baseline to Week 4	-0.9 Scores on a scale Standard Error 0.17	-1.5 Scores on a scale Standard Error 0.17	-2.0 Scores on a scale Standard Error 0.17	-1.9 Scores on a scale Standard Error 0.16
Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) Change from Baseline to Week 8	-1.2 Scores on a scale Standard Error 0.19	-1.8 Scores on a scale Standard Error 0.19	-2.3 Scores on a scale Standard Error 0.19	-2.2 Scores on a scale Standard Error 0.19
Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) Change from Baseline to Week 2	-0.9 Scores on a scale Standard Error 0.17	-1.3 Scores on a scale Standard Error 0.17	-1.6 Scores on a scale Standard Error 0.17	-1.6 Scores on a scale Standard Error 0.16
Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) Change from Baseline to Week 12	-1.5 Scores on a scale Standard Error 0.21	-2.0 Scores on a scale Standard Error 0.21	-2.6 Scores on a scale Standard Error 0.21	-2.5 Scores on a scale Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline to Week 16

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

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.

Outcome measures

Outcome measures
Measure	Placebo SC Q4W and Placebo IV Q8W n=46 Participants 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=46 Participants 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=55 Participants 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=55 Participants 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.
Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score	-3.8 Units on a scale Standard Error 0.54 • Interval 0.54 to	-6.0 Units on a scale Standard Error 0.54 • Interval 0.54 to	-5.8 Units on a scale Standard Error 0.51 • Interval 0.51 to	-6.3 Units on a scale Standard Error 0.51 • Interval 0.51 to

SECONDARY outcome

Timeframe: Baseline to Week 16

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

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.

Outcome measures

Outcome measures
Measure	Placebo SC Q4W and Placebo IV Q8W n=50 Participants 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=48 Participants 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=55 Participants 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=57 Participants 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.
Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score	-0.7 Units on a scale Standard Error 0.10 • Interval 0.1 to	-0.9 Units on a scale Standard Error 0.10 • Interval 0.1 to	-0.8 Units on a scale Standard Error 0.10 • Interval 0.1 to	-1.0 Units on a scale Standard Error 0.09 • Interval 0.09 to

Adverse Events

Placebo SC Q4W and Placebo IV Q8W

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Fasinumab 6 mg SC Q4W and Placebo IV Q8W

Serious events: 2 serious events

Other events: 35 other events

Deaths: 1 deaths

Fasinumab 9 mg SC Q4W and Placebo IV Q8W

Serious events: 3 serious events

Other events: 52 other events

Deaths: 0 deaths

Fasinumab 9 mg IV Q8W and Placebo SC Q4W

Serious events: 5 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo SC Q4W and Placebo IV Q8W n=140 participants at risk 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.	Fasinumab 6 mg SC Q4W and Placebo IV Q8W n=139 participants at risk 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.	Fasinumab 9 mg SC Q4W and Placebo IV Q8W n=139 participants at risk 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.	Fasinumab 9 mg IV Q8W and Placebo SC Q4W n=140 participants at risk 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.
Gastrointestinal disorders Nausea	1.4% 2/140 • Number of events 4 • 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. 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	2.9% 4/139 • Number of events 4 • 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. 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	5.0% 7/139 • Number of events 7 • 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. 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	0.71% 1/140 • Number of events 1 • 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. 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
Infections and infestations Nasopharyngitis	5.7% 8/140 • Number of events 8 • 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. 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	6.5% 9/139 • Number of events 9 • 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. 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	5.8% 8/139 • Number of events 9 • 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. 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	7.1% 10/140 • Number of events 10 • 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. 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
Musculoskeletal and connective tissue disorders Arthralgia	12.1% 17/140 • Number of events 22 • 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. 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	10.8% 15/139 • Number of events 26 • 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. 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	11.5% 16/139 • Number of events 24 • 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. 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	15.0% 21/140 • Number of events 26 • 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. 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
Musculoskeletal and connective tissue disorders Back pain	5.0% 7/140 • Number of events 7 • 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. 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	0.00% 0/139 • 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. 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	2.9% 4/139 • Number of events 4 • 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. 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	3.6% 5/140 • Number of events 5 • 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. 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
Musculoskeletal and connective tissue disorders Pain in extremity	8.6% 12/140 • Number of events 14 • 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. 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	2.2% 3/139 • Number of events 4 • 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. 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	3.6% 5/139 • Number of events 5 • 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. 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	2.9% 4/140 • Number of events 7 • 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. 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
Nervous system disorders Headache	6.4% 9/140 • Number of events 11 • 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. 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	6.5% 9/139 • Number of events 9 • 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. 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	6.5% 9/139 • Number of events 19 • 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. 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	6.4% 9/140 • Number of events 9 • 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. 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
Nervous system disorders Hypoaesthesia	2.9% 4/140 • Number of events 4 • 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. 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	2.9% 4/139 • Number of events 4 • 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. 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	5.0% 7/139 • Number of events 7 • 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. 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	2.1% 3/140 • Number of events 3 • 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. 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
Nervous system disorders Paraesthesia	2.9% 4/140 • Number of events 5 • 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. 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	4.3% 6/139 • Number of events 6 • 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. 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	6.5% 9/139 • Number of events 10 • 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. 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	6.4% 9/140 • Number of events 9 • 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. 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

Additional Information

Clinical Trial Administrator

Regeneron Pharmaceuticals

Phone: 844-734-6643

Email: [email protected]

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