Osteoarthritis, Hip, Osteoarthritis, Knee
Conditions
Brief summary
The primary objective of the study is to evaluate the effect of fasinumab compared to placebo on peripheral nerves in participants with pain due to Osteoarthritis (OA) of the hip or knee. The secondary objectives of the study are to: * Evaluate the efficacy of fasinumab compared to placebo in participants with pain due to OA of the hip or knee * Evaluate the safety and tolerability of fasinumab compared to placebo in participants with pain due to OA of the hip or knee * Characterize the concentrations of fasinumab in serum in participants with pain due to OA of the hip or knee * Evaluate the immunogenicity of fasinumab in participants with pain due to OA of the hip or knee.
Interventions
DRUGFasinumab
Subcutaneous (SC) every four weeks (Q4W)
OTHERPlacebo
Subcutaneous (SC) every four weeks (Q4W)
Sponsors
Teva Pharmaceutical Industries, Ltd.
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. A clinical diagnosis of 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. Moderate-to-severe pain in the index joint defined as a WOMAC average pain subscale score of ≥4 at both the screening and randomization visits 3. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments 4. A history of regular use of analgesic medications for OA pain (defined as an average of 4 days per week over the 4 weeks prior to the screening visit), including oral nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 inhibitors, opioids, paracetamol/acetaminophen, or combinations thereof 5. Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator Key
Exclusion criteria
1. History or presence at the screening visit of non-OA inflammatory joint disease (eg, rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-gout, gout, spondyloarthropathy, polymyalgia rheumatica, joint infections within the past 5 years), Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy 2. History or presence on imaging of arthropathy (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), stress fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation (prosthetic hip dislocation is eligible), knee dislocation (patella dislocation is eligible), congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures during the screening period 3. Trauma to the index joint within 3 months prior to the screening visit 4. History or presence of signs or symptoms of compression neuropathy, including carpal tunnel syndrome or sciatica 5. Participant is not a candidate for Magnetic Resonance Imaging (MRI) 6. Poorly controlled diabetes 7. Known history of human immunodeficiency virus (HIV) infection 8. Known history of ocular herpes simplex virus, herpes simplex virus pneumonia, or herpes simplex virus encephalitis 9. History of poorly controlled hypertension 10. Known history of infection with hepatitis B or C virus Note: Other protocol defined Inclusion/Exclusion apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16 | Baseline, Week 16 | Peroneal motor nerve conduction velocity was evaluated by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve conduction velocity at Week 16 was reported. |
| Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16 | Baseline, Week 16 | Peroneal motor nerve action potential amplitude was evaluated at ankle by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve action potential amplitude at Week 16 was reported. |
| Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16 | Baseline, Week 16 | Sural sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve conduction velocity at Week 16 was reported. |
| Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16 | Baseline, Week 16 | Sural sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve action potential amplitude at Week 16 was reported. |
| Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16 | Baseline, Week 16 | Ulnar sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in ulnar sensory nerve conduction velocity at Week 16 was reported. |
| Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16 | Baseline, Week 16 | Ulnar sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline ulnar sensory nerve action potential amplitude at Week 16 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Baseline up to follow-up (Week 36) | Any peripheral sensory AE (for example \[e.g.\], paraesthesia and hypoaesthesia) that required a neurology consultation. Number of peripheral sensory adverse events from baseline up to follow-up (Week 36) were reported. |
| Number of All-Cause Joint Replacement (JR) Surgery Events | Baseline up to follow-up (Week 36) | All joint replacement surgery events regardless of cause. |
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 | Baseline, Week 16 | 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. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. A negative change from baseline indicated improvement. Change from baseline in WOMAC Pain subscale score at Week 16 was reported. |
| Serum Concentration of Functional Fasinumab | Baseline, Week 1, 2, 4, 8, 12, 16 and 36 | Serum concentrations of functional Fasinumab were reported. |
| Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Baseline up to follow-up period (Week 36) | Samples for ADA evaluation were collected at baseline and at subsequent study visits. ADA variables included ADA status (+/-) and titer as follows: Total participants negative in ADA assay at all time points analyzed. Pre-existing immunoreactivity- positive response at baseline with all post-dose results negative/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/ more 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- positive response in ADA assay post first dose that is greater than/equal 9-fold over baseline level when baseline is positive. |
| Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | Baseline up to EOS (Week 64) | An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (Week 64) to evaluate the number of participants who had undergone or were scheduled for JR surgery. |
| Change From Baseline in WOMAC Physical Function Subscale Score at Week 16 | Baseline, Week 16 | Physical function referred to subject'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 (no difficulty) to 10 (extreme difficulty), where higher scores indicated worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. A negative change from baseline indicated improvement. Change from baseline in WOMAC physical function subscale score at Week 16 was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Week 16 | 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. 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. TEAE was defined as an AE with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs were reported. |
| Number of Adjudicated Arthropathy (AA) Events | Baseline up to follow-up (Week 36) | 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. Number of confirmed AA events from baseline up to follow-up (Week 36) were reported. |
| Number of AA Events Meeting Destructive Arthropathy (DA) Criteria | Baseline up to follow-up (Week 36) | AAs were evaluated to determine if they met 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. Number of confirmed AA events meeting DA criteria from baseline up to follow-up (Week 36) were reported. |
| Number of Sympathetic Nervous System (SNS) Dysfunction Events | Baseline up to follow-up (Week 36) | 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. Number of SNS dysfunction events from baseline up to follow-up (Week 36) were reported. |
Countries
Poland, United Kingdom, United States
Participant flow
Recruitment details
A total of 1604 participants were screened, out of which 180 were randomized into the study from 47 centers in North America and Europe.
Pre-assignment details
Participants who met the eligibility criteria were randomized in 1:1 ratio to receive Fasinumab or matched placebo.
Participants by arm
| Arm | Count |
|---|---|
| Fasinumab-matching Placebo Participants received Fasinumab-matching placebo SC Q4W from Day 1 through Week 12 of the 16-week treatment period. | 89 |
| Fasinumab 1 mg SC Q4W Participants received Fasinumab 1 mg SC Q4W from Day 1 through Week 12 of the 16-week treatment period. | 91 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 7 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 9 |
Baseline characteristics
| Characteristic | Fasinumab 1 mg SC Q4W | Total | Fasinumab-matching Placebo |
|---|---|---|---|
| Age, Continuous | 62.9 Years STANDARD_DEVIATION 9.1 | 62.7 Years STANDARD_DEVIATION 8.5 | 62.4 Years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 13 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 81 Participants | 164 Participants | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Peroneal Motor Nerve Action Potential Amplitude - Ankle | 4.67 Millivolts (mV) STANDARD_DEVIATION 1.7 | 4.71 Millivolts (mV) STANDARD_DEVIATION 1.85 | 4.75 Millivolts (mV) STANDARD_DEVIATION 2.01 |
| Peroneal Motor Nerve Conduction Velocity | 46.80 Meters per Second (m/sec) STANDARD_DEVIATION 3.88 | 46.83 Meters per Second (m/sec) STANDARD_DEVIATION 4.02 | 46.86 Meters per Second (m/sec) STANDARD_DEVIATION 4.17 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 78 Participants | 158 Participants | 80 Participants |
| Sex: Female, Male Female | 59 Participants | 122 Participants | 63 Participants |
| Sex: Female, Male Male | 32 Participants | 58 Participants | 26 Participants |
| Sural Sensory Nerve Action Potential Amplitude | 9.95 Microvolts (mcV) STANDARD_DEVIATION 5.67 | 9.82 Microvolts (mcV) STANDARD_DEVIATION 5.24 | 9.67 Microvolts (mcV) STANDARD_DEVIATION 4.79 |
| Sural Sensory Nerve Conduction Velocity | 52.49 m/sec STANDARD_DEVIATION 8.28 | 52.42 m/sec STANDARD_DEVIATION 8.37 | 52.35 m/sec STANDARD_DEVIATION 8.52 |
| Ulnar Sensory Nerve Action Potential Amplitude | 18.47 mcV STANDARD_DEVIATION 10.2 | 18.82 mcV STANDARD_DEVIATION 9.92 | 19.18 mcV STANDARD_DEVIATION 9.68 |
| Ulnar Sensory Nerve Conduction Velocity | 56.24 m/sec STANDARD_DEVIATION 7.45 | 56.14 m/sec STANDARD_DEVIATION 7.02 | 56.03 m/sec STANDARD_DEVIATION 6.58 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 91 |
| other Total, other adverse events | 49 / 88 | 55 / 91 |
| serious Total, serious adverse events | 6 / 88 | 3 / 91 |
Outcome results
Primary
Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16
Peroneal motor nerve action potential amplitude was evaluated at ankle by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve action potential amplitude at Week 16 was reported.
Time frame: Baseline, Week 16
Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16 | -0.2 mV | Standard Error 0.2 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16 | 0.2 mV | Standard Error 0.19 |
p-value: 0.052195% CI: [0, 0.8]MMRM
Primary
Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16
Peroneal motor nerve conduction velocity was evaluated by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve conduction velocity at Week 16 was reported.
Time frame: Baseline, Week 16
Population: The SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16 | -0.2 m/sec | Standard Error 0.46 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16 | 0.2 m/sec | Standard Error 0.42 |
p-value: 0.419295% CI: [-0.55, 1.32]Mixed Model for Repeated Measures (MMRM)
Primary
Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16
Sural sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve action potential amplitude at Week 16 was reported.
Time frame: Baseline, Week 16
Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16 | 0.5 mcV | Standard Error 0.69 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16 | 0.3 mcV | Standard Error 0.64 |
p-value: 0.775795% CI: [-1.59, 1.19]MMRM
Primary
Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16
Sural sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve conduction velocity at Week 16 was reported.
Time frame: Baseline, Week 16
Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16 | -2.9 m/sec | Standard Error 0.9 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16 | -1.6 m/sec | Standard Error 0.83 |
p-value: 0.159395% CI: [-0.52, 3.15]MMRM
Primary
Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16
Ulnar sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline ulnar sensory nerve action potential amplitude at Week 16 was reported.
Time frame: Baseline, Week 16
Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16 | 2.4 mcV | Standard Error 1.21 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16 | 1.4 mcV | Standard Error 1.12 |
p-value: 0.420395% CI: [-3.3, 1.39]MMRM
Primary
Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16
Ulnar sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in ulnar sensory nerve conduction velocity at Week 16 was reported.
Time frame: Baseline, Week 16
Population: SAF included all randomized participants who received any study drug and was based on the treatment received (as treated). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16 | -0.7 m/sec | Standard Error 0.74 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16 | -1.1 m/sec | Standard Error 0.68 |
p-value: 0.606395% CI: [-1.87, 1.09]MMRM
Secondary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16
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. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. A negative change from baseline indicated improvement. Change from baseline in WOMAC Pain subscale score at Week 16 was reported.
Time frame: Baseline, Week 16
Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 | -1.19 Score on a Scale | Standard Error 0.359 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 | -2.52 Score on a Scale | Standard Error 0.335 |
p-value: 0.00195% CI: [-2.123, -0.538]MMRM
Secondary
Change From Baseline in WOMAC Physical Function Subscale Score at Week 16
Physical function referred to subject'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 (no difficulty) to 10 (extreme difficulty), where higher scores indicated worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. A negative change from baseline indicated improvement. Change from baseline in WOMAC physical function subscale score at Week 16 was reported.
Time frame: Baseline, Week 16
Population: FAS included all randomized participants and was based on the treatment allocated (as randomized). Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline in WOMAC Physical Function Subscale Score at Week 16 | -0.83 Score on a Scale | Standard Error 0.366 |
| Fasinumab 1 mg SC Q4W | Change From Baseline in WOMAC Physical Function Subscale Score at Week 16 | -2.24 Score on a Scale | Standard Error 0.341 |
p-value: 0.000595% CI: [-2.212, -0.625]MMRM
Secondary
Number of AA Events Meeting Destructive Arthropathy (DA) Criteria
AAs were evaluated to determine if they met 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. Number of confirmed AA events meeting DA criteria from baseline up to follow-up (Week 36) were reported.
Time frame: Baseline up to follow-up (Week 36)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated). Overall Number of Participants Analyzed signifies those participants who had confirmed AA events.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab 1 mg SC Q4W | Number of AA Events Meeting Destructive Arthropathy (DA) Criteria | 0 Destructive Arthropathy (DA) Events |
Secondary
Number of 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. Number of confirmed AA events from baseline up to follow-up (Week 36) were reported.
Time frame: Baseline up to follow-up (Week 36)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Adjudicated Arthropathy (AA) Events | 0 Adjudicated Arthropathy (AA) Events |
| Fasinumab 1 mg SC Q4W | Number of Adjudicated Arthropathy (AA) Events | 4 Adjudicated Arthropathy (AA) Events |
Secondary
Number of All-Cause Joint Replacement (JR) Surgery Events
All joint replacement surgery events regardless of cause.
Time frame: Baseline up to follow-up (Week 36)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of All-Cause Joint Replacement (JR) Surgery Events | 4 Joint Replacement (JR) Surgery Events |
| Fasinumab 1 mg SC Q4W | Number of All-Cause Joint Replacement (JR) Surgery Events | 5 Joint Replacement (JR) Surgery Events |
Secondary
Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug
An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (Week 64) to evaluate the number of participants who had undergone or were scheduled for JR surgery.
Time frame: Baseline up to EOS (Week 64)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | 1 Joint Replacement (JR) Surgery Events |
| Fasinumab 1 mg SC Q4W | Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | 0 Joint Replacement (JR) Surgery Events |
Secondary
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA)
Samples for ADA evaluation were collected at baseline and at subsequent study visits. ADA variables included ADA status (+/-) and titer as follows: Total participants negative in ADA assay at all time points analyzed. Pre-existing immunoreactivity- positive response at baseline with all post-dose results negative/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/ more 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- positive response in ADA assay post first dose that is greater than/equal 9-fold over baseline level when baseline is positive.
Time frame: Baseline up to follow-up period (Week 36)
Population: The anti-drug antibody (ADA) analysis set included all treated participants who received any study drug and had at least 1 qualified (non-missing) ADA result following the first dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Pre-Existing Immunoreactivity | 1 Participants |
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Boosted Response | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent Response | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Persistent | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Transient | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Indeterminate | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Transient | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Pre-Existing Immunoreactivity | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Persistent | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Boosted Response | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent: Indeterminate | 0 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) | Treatment-Emergent Response | 0 Participants |
Secondary
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. 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. TEAE was defined as an AE with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs were reported.
Time frame: Baseline up to Week 16
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 57 Participants |
| Fasinumab 1 mg SC Q4W | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 63 Participants |
Secondary
Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation
Any peripheral sensory AE (for example \[e.g.\], paraesthesia and hypoaesthesia) that required a neurology consultation. Number of peripheral sensory adverse events from baseline up to follow-up (Week 36) were reported.
Time frame: Baseline up to follow-up (Week 36)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Decreased vibratory sense | 0 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Neuropathy peripheral | 1 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Hypoaesthesia | 1 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Paraesthesia | 1 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Carpal tunnel syndrome | 4 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 1 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Paraesthesia | 2 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 1 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Carpal tunnel syndrome | 4 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 1 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Decreased vibratory sense | 3 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 1 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Hypoaesthesia | 0 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 1 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Neuropathy peripheral | 3 Peripheral Sensory Adverse Events (AEs) |
Secondary
Number of 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. Number of SNS dysfunction events from baseline up to follow-up (Week 36) were reported.
Time frame: Baseline up to follow-up (Week 36)
Population: SAF included all randomized participants who received any study drug and was based on the actual treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Sympathetic Nervous System (SNS) Dysfunction Events | 0 SNS Dysfunction Events |
| Fasinumab 1 mg SC Q4W | Number of Sympathetic Nervous System (SNS) Dysfunction Events | 0 SNS Dysfunction Events |
Secondary
Serum Concentration of Functional Fasinumab
Serum concentrations of functional Fasinumab were reported.
Time frame: Baseline, Week 1, 2, 4, 8, 12, 16 and 36
Population: The Pharmacokinetic (PK) Analysis Set included all treated participants who received any study drug and who had at least 1 non-missing drug concentration result following the first dose of study drug. Here, Number Analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 16 | 0.0824 Milligrams per Liter (mg/L) | Standard Deviation 0.049 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 36 | 0 Milligrams per Liter (mg/L) | Standard Deviation 0 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Baseline | 0 Milligrams per Liter (mg/L) | Standard Deviation 0 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 1 | 0.0864 Milligrams per Liter (mg/L) | Standard Deviation 0.029 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 2 | 0.0820 Milligrams per Liter (mg/L) | Standard Deviation 0.025 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 4 | 0.0525 Milligrams per Liter (mg/L) | Standard Deviation 0.018 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 8 | 0.0780 Milligrams per Liter (mg/L) | Standard Deviation 0.0326 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab | Week 12 | 0.0802 Milligrams per Liter (mg/L) | Standard Deviation 0.04 |