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CompletedNCT03304379FACT OA2Updated Feb 24, 2023Results posted

Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip

A Phase 3 interventional study of Fasinumab and Diclofenac in Osteoarthritis, Knee and Osteoarthritis, Hip, sponsored by Regeneron Pharmaceuticals. Completed at 71 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-24.

Sponsored by Regeneron Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,650
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The primary objective of the study is to evaluate the efficacy of fasinumab compared to placebo, when administered for up to 24 weeks in patients with pain due to osteoarthritis (OA) of the knee or hip.

The secondary objectives of the study are:

  • To evaluate the efficacy of fasinumab compared to non-steroidal anti-inflammatory drugs (NSAID)s, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip
  • To assess the safety and tolerability of fasinumab compared to placebo and compared to NSAIDs, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip
02

Conditions studied

  • Osteoarthritis, Knee
  • Osteoarthritis, Hip
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria (additional criteria may apply at screening):

  1. A clinical diagnosis of osteoarthritis (OA) of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit.
  2. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol to be taken as needed with a maximum daily dose of 2500 mg [countries where 500 mg strength tablets/capsules are available] or 2600 mg [countries where 325 mg strength tablets/capsules are available])
  3. A history of at least 12 weeks of inadequate pain relief or intolerance to analgesics used for pain due to OA of the knee or hip
  4. Currently using a stable dose of NSAID
  5. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment

Key Exclusion Criteria (additional criteria may apply at screening):

  1. Non-compliance with the numeric rating scale (NRS) recording during the pre-randomization period
  2. History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy
  3. History or presence on imaging of arthropathy, hip or knee dislocation, extensive subchondral cysts, evidence of severe structural damage, bone collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures
  4. Trauma to the index joint within 3 months prior to the screening visit
  5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening
  6. Patient is not a candidate for magnetic resonance imaging (MRI)
  7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed
  8. History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
  9. Evidence of autonomic neuropathy as defined in the schedule of assessments (SoAs)
  10. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
  11. Use of systemic corticosteroids within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit
  12. Exposure to an anti-NGF antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies
  13. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 20 weeks after the last dose
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
1,650 participants (actual)

Study arms

  • Experimental
    Dosing regimen 1

    Drug: Fasinumab · Drug: Matching placebo

  • Experimental
    Dosing regimen 2

    Other: Diclofenac · Drug: Matching placebo

  • Experimental
    Dosing regimen 3

    Other: Celecoxib · Drug: Matching placebo

  • Experimental
    Dosing regimen 4

    Drug: Matching placebo

Interventions

  • DrugFasinumab

    Solution for injection in pre-filled syringe

    Also known as: REGN475, MT-5547

  • OtherDiclofenac

    NSAID active comparator (capsule)

    Also known as: ZORVOLEX

  • OtherCelecoxib

    NSAID active comparator (capsule)

    Also known as: CELEBREX

  • DrugMatching placebo

    Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)

05

What researchers measure

Primary outcomes

  1. Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

    WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

    Time frame: Baseline up to Week 24

  2. Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

    Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

    Time frame: Baseline up to Week 24

Secondary outcomes

  1. Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo

    WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.

    Time frame: Baseline up to Week 24

  2. Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

    The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

    Time frame: Baseline up to Week 24

  3. Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

    WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

    Time frame: Baseline up to Week 24

  4. Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

    Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

    Time frame: Baseline up to Week 24

  5. Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

    The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

    Time frame: Baseline up to Week 24

  6. Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale

    Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain.

    Time frame: Baseline up to Week 24

  7. Number of Participants With Adjudicated Arthropathy (AA) Events

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

    Time frame: Baseline up to follow-up period (Week 44)

  8. Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria

    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 OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.

    Time frame: Baseline up to follow-up period (Week 44)

  9. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.

    Time frame: Baseline up to follow-up period (Week 44)

  10. Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events

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

    Time frame: Baseline up to follow-up period (Week 44)

  11. Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)

    Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI).

    Time frame: Baseline up to Week 44

  12. Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24

    Number of participants who underwent a JR surgery from baseline up to Week 24 were reported.

    Time frame: Baseline up to Week 24

  13. Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44

    Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported.

    Time frame: Baseline up to Week 44

  14. Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)

    An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery.

    Time frame: At Week 72

  15. Serum Concentrations of Functional Fasinumab

    Time frame: At Weeks 0, 4, 8, 16, 24 and 44

  16. Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development

    Immunogenicity was characterized by ADA responses \& titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses \< 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, \>= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing.

    Time frame: Baseline up to Week 44

06

Results

Posted Feb 24, 2023

Participant flow

A total of 4531 participants were screened in this study. Out of which, 1650 participants were randomized to 1 of the following arms: Fasinumab (1 milligram \[mg\]), non-steroidal anti-inflammatory drug (NSAIDs), matched placebo, Fasinumab 3 and 6 mg. Screen failure was mostly due to inclusion criteria not met/exclusion criteria met. Eligible participants were randomized to receive placebo matched to Fasinumab/NSAIDs, NSAIDs (Diclofenac and Celecoxib) and Fasinumab 1 mg.

Participant flow — Overall Study
MilestonePlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mg
Started3086126125959
Full analysis set (fas)30861261200
Safety analysis set (saf)30960960900
Urgent safety measure set (usms)0005959
Completed treatment21843645400
Completed2384714634242
Not completed701411491717
Withdrew: Protocol violation810502
Withdrew: Adverse event4201710
Withdrew: Lack of efficacy17162000
Withdrew: Physician decision6106910
Withdrew: Withdrawal by subject26586635
Withdrew: Lost to follow-up8243540
Withdrew: Death12000
Withdrew: Other01000

Outcome measures

PrimaryChange From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
Score on a ScalePlaceboFasinumab 1 mg
FAS-2.21 ± 0.165-2.84 ± 0.127
mFAS-2.01 ± 0.182-2.78 ± 0.141
Statistical analysis
  • Placebo vs Fasinumab 1 mg · MMRM · p = = 0.0003 (Threshold for significance at 0.05 level.) · Least square (ls) mean difference: -0.63 · 95% CI -0.971 to -0.286
  • Placebo vs Fasinumab 1 mg · MMRM · p = > 0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -0.77 · 95% CI -1.154 to -0.383
PrimaryChange From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
Score on a ScalePlaceboFasinumab 1 mg
FAS-2.02 ± 0.164-2.65 ± 0.125
mFAS-1.80 ± 0.180-2.62 ± 0.138
Statistical analysis
  • Placebo vs Fasinumab 1 mg · MMRM · p = = 0.0003 (Threshold for significance at 0.05 level.) · Ls mean difference: -0.64 · 95% CI -0.981 to -0.290
  • Placebo vs Fasinumab 1 mg · MMRM · p = <0.0001 (Threshold for significance at 0.05 level) · Ls mean difference: -0.82 · 95% CI -1.198 to -0.443
SecondaryPercentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo

WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.

Time frame:
Baseline up to Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo
Percentage of ParticipantsPlaceboFasinumab 1 mg
Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to Placebo48.759.8
Statistical analysis
  • Placebo vs Fasinumab 1 mg · Cochran-Mantel-Haenszel · p = = 0.0013 (Threshold for significance at 0.05 level.) · Odds ratio (or): 1.581 · 95% CI 1.195 to 2.092
SecondaryChange From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo

The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
Score on a ScalePlaceboFasinumab 1 mg
Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo-0.66 ± 0.063-0.81 ± 0.047
Statistical analysis
  • Placebo vs Fasinumab 1 mg · MMRM · p = = 0.0365 (Threshold for significance at 0.05 level.) · Ls mean difference: -0.14 · 95% CI -0.28 to -0.009
SecondaryChange From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
Score on a ScaleNSAIDsFasinumab 1 mg
FAS-2.60 ± 0.128-2.84 ± 0.127
mFAS-2.48 ± 0.140-2.78 ± 0.141
SecondaryChange From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
Score on a ScaleNSAIDsFasinumab 1 mg
FAS-2.33 ± 0.127-2.65 ± 0.125
mFAS-2.26 ± 0.140-2.62 ± 0.138
SecondaryChange From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs

The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
Score on a ScaleNSAIDsFasinumab 1 mg
Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs-0.75 ± 0.048-0.81 ± 0.047
SecondaryChange From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale

Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain.

Time frame:
Baseline up to Week 24
Reported as:
Least squares mean · Score on a Scale
Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale
Score on a ScalePooled PlaceboNSAIDsFasinumab 1 mg
Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale-1.85 ± 0.130-2.13 ± 0.101-2.51 ± 0.100
SecondaryNumber of Participants With Adjudicated Arthropathy (AA) Events

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

Time frame:
Baseline up to follow-up period (Week 44)
Reported as:
Count of participants · Participants
Number of Participants With Adjudicated Arthropathy (AA) Events
ParticipantsPooled PlaceboNSAIDsFasinumab 1 mg
Number of Participants With Adjudicated Arthropathy (AA) Events5934
SecondaryNumber of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria

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 OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.

Time frame:
Baseline up to follow-up period (Week 44)
Reported as:
Count of participants · Participants
Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria
ParticipantsPooled PlaceboNSAIDsFasinumab 1 mg
Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria002
SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.

Time frame:
Baseline up to follow-up period (Week 44)
Reported as:
Count of participants · Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
ParticipantsPooled PlaceboNSAIDsFasinumab 1 mg
Number of Participants With Treatment Emergent Adverse Events (TEAEs)186406403
SecondaryNumber of Participants With Sympathetic Nervous System (SNS) Dysfunction Events

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

Time frame:
Baseline up to follow-up period (Week 44)
Reported as:
Count of participants · Participants
Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events
ParticipantsPooled PlaceboNSAIDsFasinumab 1 mg
Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events000
SecondaryNumber of Participants With At-least One Peripheral Sensory Adverse Events (AEs)

Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI).

Time frame:
Baseline up to Week 44
Reported as:
Count of participants · Participants
Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)
ParticipantsPlaceboNSAIDsFasinumab 1 mg
Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)82431
SecondaryNumber of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24

Number of participants who underwent a JR surgery from baseline up to Week 24 were reported.

Time frame:
Baseline up to Week 24
Reported as:
Count of participants · Participants
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24
ParticipantsPlaceboNSAIDsFasinumab 1 mg
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24273
SecondaryNumber of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44

Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported.

Time frame:
Baseline up to Week 44
Reported as:
Count of participants · Participants
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44
ParticipantsPlaceboNSAIDsFasinumab 1 mg
Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 4461310
SecondaryNumber of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)

An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery.

Time frame:
At Week 72
Reported as:
Count of participants · Participants
Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)
ParticipantsPlaceboNSAIDsFasinumab 1 mg
Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)112921
SecondarySerum Concentrations of Functional Fasinumab
Time frame:
At Weeks 0, 4, 8, 16, 24 and 44
Reported as:
Mean · Milligrams per Liter (mg/L)
Serum Concentrations of Functional Fasinumab
Milligrams per Liter (mg/L)Fasinumab 1 mg
Week 00.000155 ± 0.002
Week 40.0469 ± 0.0179
Week 80.0644 ± 0.0275
Week 160.0738 ± 0.0380
Week 240.0713 ± 0.0379
Week 440.000349 ± 0.00476
SecondaryNumber of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development

Immunogenicity was characterized by ADA responses \& titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses \< 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, \>= 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing.

Time frame:
Baseline up to Week 44
Reported as:
Count of participants · Participants
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development
ParticipantsPlaceboNSAIDsFasinumab 1 mg
Pre-Existing Immunoreactivity10915
Treated-Boosted Response000
Treatment-Emergent Response314

Adverse events

Collected over First dose to week 44. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo1/309 (0.3%)20/309 (6.5%)121/309 (39.2%)
NSAIDs3/609 (0.5%)45/609 (7.4%)263/609 (43.2%)
Fasinumab 1mg Q4W1/609 (0.2%)35/609 (5.7%)261/609 (42.9%)
Fasinumab 3mg Q4W0/58 (0%)5/58 (8.6%)17/58 (29.3%)
Fasinumab 6mg Q8W0/59 (0%)2/59 (3.4%)15/59 (25.4%)
Most frequent serious events
Showing 10 of 77
Most frequent serious events
EventPlaceboNSAIDsFasinumab 1mg Q4WFasinumab 3mg Q4WFasinumab 6mg Q8W
Rapidly progressive osteoarthritisMusculoskeletal and connective tissue disorders2/3090/6098/6092/582/59
ArthralgiaMusculoskeletal and connective tissue disorders0/3091/6090/6091/580/59
OsteoarthritisMusculoskeletal and connective tissue disorders3/3096/6091/6091/580/59
Knee arthroplastySurgical and medical procedures1/3094/6092/6091/580/59
Atrioventricular block completeCardiac disorders0/3090/6090/6091/580/59
Subchondral insufficiency fractureMusculoskeletal and connective tissue disorders0/3090/6090/6091/580/59
Joint arthroplastySurgical and medical procedures1/3093/6091/6090/580/59
Hip arthroplastySurgical and medical procedures1/3093/6091/6090/580/59
Atrial fibrillationCardiac disorders1/3092/6090/6090/580/59
Gastrointestinal haemorrhageGastrointestinal disorders0/3090/6092/6090/580/59
Most frequent other events
Most frequent other events
EventPlaceboNSAIDsFasinumab 1mg Q4WFasinumab 3mg Q4WFasinumab 6mg Q8W
HeadacheNervous system disorders48/309107/60995/6092/582/59
ArthralgiaMusculoskeletal and connective tissue disorders36/30978/60982/6094/583/59
Urinary tract infectionInfections and infestations25/30935/60950/6091/582/59
Back painMusculoskeletal and connective tissue disorders17/30944/60946/6091/581/59
NasopharyngitisInfections and infestations22/30938/60929/6092/581/59
Upper respiratory tract infectionInfections and infestations15/30930/60930/6093/581/59
Blood creatine phosphokinase increasedInvestigations3/3095/6095/6093/583/59
Muscle strainInjury, poisoning and procedural complications0/3094/6096/6093/581/59
Ligament sprainInjury, poisoning and procedural complications2/3094/6095/6090/583/59

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
Mean62.0 ± 9.3062.3 ± 9.4162.1 ± 9.1362.8 ± 9.3861.5 ± 9.5562.2 ± 9.28
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
Female22241843636341146
Male861941762325504
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
Hispanic or Latino204431510110
Not Hispanic or Latino28556858154491537
Unknown or Not Reported300003
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
American Indian or Alaska Native002002
Asian33575483155
Native Hawaiian or Other Pacific Islander101002
Black or African American601341321216354
White20239640539401082
More than one race1124180053
Unknown or Not Reported110002
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score(Score on a scale)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
Mean6.42 ± 1.3946.38 ± 1.3446.46 ± 1.3216.43 ± 1.4016.54 ± 1.2796.42 ± 1.344
WOMAC Physical Function Subscale Scores
WOMAC Physical Function Subscale Scores(Score on a scale)PlaceboNSAIDsFasinumab 1 mgFasinumab 3 mgFasinumab 6 mgTotal
Mean6.40 ± 1.4956.32 ± 1.4186.39 ± 1.4626.50 ± 1.3506.34 ± 1.3926.37 ± 1.445
07

Study locations

71 sites
  • Pinnacle Research Group, Llc
    Anniston, Alabama 36207, United States
  • Horizon Research Partners
    Mobile, Alabama 36608, United States
  • Clinical Research Advantage, Inc./Warner Family Practice, PC
    Chandler, Arizona 85224, United States
  • Synexus Central Phoenix Medical Clinic
    Phoenix, Arizona 85020, United States
  • Clinical Research Consortium Arizona
    Tempe, Arizona 85283, United States
  • Advance Research Center
    Anaheim, California 92805, United States
  • TriWest Research Associates, LLC
    El Cajon, California 92020, United States
  • Paragon Rx Clinical Research, Inc.
    Garden Grove, California 92840, United States
  • Catalina Research Institute, LLC
    Montclair, California 91763, United States
  • Sierra Clinical Research
    Roseville, California 95661, United States
  • UC Davis Center for Musculoskeletal Health
    Sacramento, California 95817, United States
  • Advanced Research Center, Inc
    San Diego, California 92103, United States
  • California Research Foundation
    San Diego, California 92123, United States
  • Paragon Rx Clinical Research, Inc
    Santa Ana, California 92703, United States
  • Encompass Clinical Research
    Spring Valley, California 91978, United States
  • Westlake Medical Research
    Thousand Oaks, California 91360, United States
  • Synexus Clinical Research US, Inc.
    Vista, California 92083, United States
  • Mountain View Clinical Research
    Denver, Colorado 80209, United States
  • New England Research Associates, LLC
    Bridgeport, Connecticut 06606, United States
  • CRM of Greater New Haven, LLC
    Hamden, Connecticut 06157, United States
  • Stamford Therapeutics Consortium
    Stamford, Connecticut 06905, United States
  • Avail Clinical Research, LLC
    DeLand, Florida 32720, United States
  • Lakes Research, LLC
    Miami Lakes, Florida 33014, United States
  • AMB Research Center, Inc
    Miami, Florida 33144, United States
  • Allied Biomedical Research Institute
    Miami, Florida 33155, United States
  • Bioclinica Research
    Orlando, Florida 32806, United States
  • Gulf Region Clinical Research institute
    Pensacola, Florida 32514, United States
  • Integral Rheumatology & Immunology Specialists (IRIS)
    Plantation, Florida 33324, United States
  • Progressive Medical Research
    Port Orange, Florida 32127, United States
  • Drug Studies America
    Marietta, Georgia 30060, United States
  • Georgia Institute For Clinical Research LLC
    Marietta, Georgia 30060, United States
  • North Georgia Clinical Research
    Woodstock, Georgia 30189, United States
  • Chicago Clinical Research Institute, Inc
    Chicago, Illinois 60607, United States
  • Affinity Clinical Research Institute
    Oak Lawn, Illinois 60453, United States
  • Clinical Research Advantage, Inc.
    Evansville, Indiana 47714, United States
  • MediSphere Medical Research Center, LLC
    Evansville, Indiana 47714, United States
  • L-MARC Research Center
    Louisville, Kentucky 40213, United States
  • Tandem Clinical Research
    Marrero, Louisiana 70072, United States
  • Tufts Medical Center, Inc.
    Boston, Massachusetts 02111, United States
  • Great Lakes Research Group, Inc.
    Bay City, Michigan 48706, United States
  • Onyx Clinical Research
    Caro, Michigan 48723, United States
  • Synexus Clinical Research US, Inc.
    Richfield, Minnesota 55423, United States
  • Skyline Medical Center /Radiant Research, Inc.
    Elkhorn, Nebraska 68022, United States
  • Meridian Clinical Research Associates, LLC
    Omaha, Nebraska 68134, United States
  • Robert Kaplan, D.O.
    Las Vegas, Nevada 89144, United States
  • Amici Clinical Research, LLC
    Raritan, New Jersey 08869, United States
  • Albuquerque Clinical Trials, Inc.
    Albuquerque, New Mexico 87102, United States
  • Drug Trial Brooklyn
    Brooklyn, New York 11230, United States
  • Northwell Health
    Great Neck, New York 11021, United States
  • Drug Trials America
    Hartsdale, New York 10530, United States
  • Upstate Clinical Research Associates, LLC
    Williamsville, New York 14221, United States
  • Carolina Research Center
    Shelby, North Carolina 28150, United States
  • PMG Research of Wilmington LLC
    Wilmington, North Carolina 28401, United States
  • The Center For Clinical Research
    Winston-Salem, North Carolina 27103, United States
  • New Horizons Clinical Research
    Cincinnati, Ohio 45242, United States
  • Aventiv Research Inc
    Columbus, Ohio 43213, United States
  • DOC Clinical Research
    Dayton, Ohio 45432, United States
  • Center for Orthopaedics and Sports Medicine
    Indiana, Pennsylvania 15701, United States
  • Radiant Research, Inc.
    Anderson, South Carolina 29621, United States
  • Piedmont Comprehensive Pain Management Group
    Greenville, South Carolina 29601, United States
  • Radiant Research, Inc.
    Greer, South Carolina 29651, United States
  • Piedmont Research Partners, LLC
    Indian Land, South Carolina 29707, United States
  • Coastal Carolina Research Center at LowCountry Orthopaedics
    North Charleston, South Carolina 29406, United States
  • ACME Research, LLC
    Orangeburg, South Carolina 29118, United States
  • Office of Dr.Ramesh C. Gupta MD
    Memphis, Tennessee 38119, United States
  • West Texas Clinical Research
    Lubbock, Texas 79410, United States
  • Clinical Investigations Of Texas
    Plano, Texas 75075, United States
  • Synexus USA
    Plano, Texas 75093, United States
  • Charlottesville Medical Research Center LLC
    Charlottesville, Virginia 22911, United States
  • Health Research of Hampton Roads, Inc
    Newport News, Virginia 23606, United States
  • Spokane Joint Replacement Center
    Spokane, Washington 99218, United States
08

References and documents

Study documents

  • Study protocol · Jul 11, 2018
  • Statistical analysis plan · Apr 16, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03304379
Lead sponsor
Regeneron Pharmaceuticals
Collaborators
Teva Pharmaceutical Industries, Ltd.
Responsible party
Sponsor
First posted
Oct 9, 2017
Start date
Oct 26, 2017
Primary completion
Dec 13, 2019
Completion
Nov 9, 2020
Results posted
Feb 24, 2023
Last update
Feb 24, 2023

Study contacts

Clinical Trial Management
study director · Regeneron Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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