Clinical Trial Results:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Fasinumab in Patients with Moderate to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee
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Summary
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EudraCT number |
2017-001943-12 |
Trial protocol |
GB HU ES |
Global end of trial date |
03 May 2019
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Results information
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Results version number |
v2(current) |
This version publication date |
17 Oct 2021
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First version publication date |
15 May 2020
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R475-PN-1612
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03285646 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Acronym: FACT CLBP 1 | ||
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Sponsors
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Sponsor organisation name |
Regeneron Pharmaceuticals, Inc.
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Sponsor organisation address |
777 Old Saw Mill River Rd., Tarrytown, United States, 10591
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Public contact |
Study Director, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
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Scientific contact |
Study Director, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Jun 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 May 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of fasinumab in relieving chronic low back pain (CLBP) as compared to placebo in subjects with a clinical diagnosis of moderate-to-severe non-radicular CLBP and osteoarthritis (OA) of the knee or hip when treated for up to 16 weeks.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Oct 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 63
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Worldwide total number of subjects |
63
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
45
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From 65 to 84 years |
18
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were screened for study eligibility across the United States. Of the 377 subjects screened, 63 met eligibility criteria. The most frequently reported reason for non-randomization was inclusion criteria not met and/or exclusion criteria met (224 subjects):139 did not meet inclusion criteria, 86 subjects met exclusion criteria. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
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. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Data analyst, Carer, Assessor | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fasinumab-matching Placebo | ||||||||||||||||||||||||
Arm description |
Subjects received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects were administered SC injection of placebo matched to fasinumab Q4W into abdomen, thigh or upper arm
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Arm title
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Fasinumab 3 mg SC Q4W | ||||||||||||||||||||||||
Arm description |
Subjects received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Fasinumab
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Investigational medicinal product code |
REGN475
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects were administered 3 mg SC injection of fasinumab Q4W into abdomen, thigh or upper arm
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Baseline characteristics reporting groups
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Reporting group title |
Fasinumab-matching Placebo
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Reporting group description |
Subjects received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fasinumab 3 mg SC Q4W
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Reporting group description |
Subjects received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fasinumab-matching Placebo
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Reporting group description |
Subjects received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||
Reporting group title |
Fasinumab 3 mg SC Q4W
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Reporting group description |
Subjects received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | ||
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End point title |
Change from Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score [1] | ||||||||||||||||||||||||||||||
End point 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. Subjects 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.
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End point type |
Primary
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End point timeframe |
Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Placebo subjects were not included in the concentration analysis |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Change from Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | |||||||||||||||||||||||||||
End point description |
The RMDQ is a self-administered, health status measure for lower back pain (LBP). It measures pain and function, using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores are indicative of better function.
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, Week 16
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Change from Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | |||||||||||||||||||||||||||
End point description |
The PGA of LBP is a subject 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.
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, Week 16
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Change from Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | |||||||||||||||||||||||||||
End point description |
The BPI-sf is a self-administered questionnaire for subjects 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.
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End point type |
Secondary
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End point timeframe |
Week 2, Week 4, Week 8, Week 12, Week 16
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Number of Subjects Achieving ≥30% Reduction from Baseline to Week 16 in Average Daily LBPI NRS Score | |||||||||
End point 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. Subjects 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.
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End point type |
Secondary
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End point timeframe |
Week 16
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Adjudicated Arthropathy (AA) Events | |||||||||
End point description |
Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.
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End point type |
Secondary
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End point timeframe |
Up to Week 36
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Adjudicated Arthropathy (AA) Events meeting Destructive Arthropathy (DA) Criteria | |||||||||
End point description |
Destructive arthropathy (DA) is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive Osteoarthritis type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis.
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End point type |
Secondary
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End point timeframe |
Up to Week 36
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Treatment-Emergent Adverse Events (TEAEs) | |||||||||
End point description |
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period.
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End point type |
Secondary
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End point timeframe |
Up to Week 16
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Sympathetic Nervous System (SNS) Dysfunction Events | |||||||||
End point description |
Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.
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End point type |
Secondary
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End point timeframe |
Up to Week 36
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Peripheral Sensory Adverse Events (AEs) that Require a Neurology Consultation | |||||||||||||||
End point description |
Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation.
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End point type |
Secondary
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End point timeframe |
Up to Week 36
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Number of All-Cause Joint Replacement (JR) Surgery Events | |||||||||
End point description |
All joint replacement surgery events regardless of cause.
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End point type |
Secondary
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End point timeframe |
Up to Week 36
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | |||||||||
End point description |
An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (week 12) to evaluate the number of participants who had undergone or were scheduled for JR surgery.
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End point type |
Secondary
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End point timeframe |
Up to Week 64
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Subjects With at Least One Positive Anti-Drug Antibody (ADA) Assay | |||||||||||||||||||||||||||
End point description |
Samples for Anti-Drug Antibody (ADA) evaluation were collected at baseline and at subsequent study visits. ADA variables include ADA status (+ or -) and titer as follows: Total subjects 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.
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End point type |
Secondary
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End point timeframe |
16 Weeks
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Serum Concentration of Functional Fasinumab Over Time [2] | ||||||||||||||||||
End point description |
Summary of mean concentration of functional fasinumab are presented by nominal time point.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 2, Week 4, Week 8, Week 16
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Placebo subjects were not included in the concentration analysis |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36)
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Adverse event reporting additional description |
Reported adverse events (AEs) are AEs that developed/worsened from the time of the first administration of study drug until the end of the follow up period (week 36)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Fasinumab-matching Placebo
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Reporting group description |
Subjects received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fasinumab 3 mg SC Q4W
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Reporting group description |
Subjects received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Subjects 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| As a result of an urgent safety measure and discontinuation of study drug, the small number of subjects enrolled in this study limited the interpretability of the efficacy results. | |||||||
