Osteoarthritis, Hip, Osteoarthritis, Knee
Conditions
Brief summary
The objective of this exploratory study is to evaluate the cellular and connective tissue composition of joints from patients with Osteoarthritis (OA) who have been treated with fasinumab, compared with those treated with placebo or Non-steroidal anti-inflammatory drugs (NSAIDs).
Interventions
DRUGFasinumab
Study drug will be administered in the parent study. Samples will be collected for participants who voluntarily elect to have knee or hip joint arthroplasty during the parent study
DRUGNaproxen
Naproxen will be administered in the parent study. Samples will be collected for participants who voluntarily elect to have knee or hip joint arthroplasty during the parent study
DRUGDiclofenac
Diclofenac will be administered in the parent study. Samples will be collected for participants who voluntarily elect to have knee or hip joint arthroplasty during the parent study
DRUGCelecoxib
Celecoxib will be administered in the parent study. Samples will be collected for participants who voluntarily elect to have knee or hip joint arthroplasty during the parent study
DRUGPlacebo
Matching Placebo will be administered in the parent study. Samples will be collected for participants who voluntarily elect to have knee or hip joint arthroplasty during the parent study
Sponsors
Teva Pharmaceutical Industries, Ltd.
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Previously randomized to R475-PN-1523 (NCT02683239), R475-OA-1611 (NCT03161093), or R475-OA-1688 (NCT03304379) and received at least 1 dose of study drug * Notified the site that they are planning a knee or hip arthroplasty during the parent study between randomization and 24 weeks after the last dose of subcutaneous (SC) study drug * Patient's surgeon/pathologist is willing to coordinate with the site regarding preparation, storage, and shipping of joint tissue samples collected during arthroplasty surgery
Exclusion criteria
* None Note: Other protocol Inclusion criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants by Degree of Synovial Lymphocytic Inflammation | Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months | Inflammatory cells including lymphocytes, mast cells, neutrophils, and eosinophils were scored by presence and degree (None present, Slight/Mild, Moderate, Marked/Band). |
| Number of Participants by Degree of Cartilage Loss | Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months | Microscopic articular features including degree of cartilage were evaluated and scored (Superficial Fibrillation, Deep fissuring, Loss to Tide Mark, Loss to Exposed Bone). |
| Number of Participants by Degree of Bony Changes | Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months | Microscopic articular features including degree of bony changes were evaluated and scored (Normal, Sclerosis \[Lamellar/Mixed\], Subarticular Fracture/Collapse). |
Countries
Poland, United Kingdom, United States
Participant flow
Pre-assignment details
This study only included participants that received at least 1 dose of study drug in one of the 3 parent studies: R475-PN-1523 (NCT02683239), R475-OA-1611 (NCT03161093), or R475-OA-1688 (NCT03304379).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was administered in the parent studies; joint tissue samples for this study were collected for participants who voluntarily elected to have knee or hip joint arthroplasty during the parent studies | 2 |
| Non-steroidal Anti-inflammatory Drug (NSAID) Non-steroidal anti-inflammatory drugs (NSAID) were administered in the parent studies; joint tissue samples for this study were collected for participants who voluntarily elected to have knee or hip joint arthroplasty during the parent studies | 5 |
| Fasinumab Fasinumab was administered in the parent studies; joint tissue samples for this study were collected for participants who voluntarily elected to have knee or hip joint arthroplasty during the parent studies | 13 |
| Total | 20 |
Baseline characteristics
| Characteristic | Placebo | Non-steroidal Anti-inflammatory Drug (NSAID) | Fasinumab | Total |
|---|---|---|---|---|
| Age, Continuous | 60.5 Years STANDARD_DEVIATION 7.8 | 60.2 Years STANDARD_DEVIATION 7.7 | 67.3 Years STANDARD_DEVIATION 8.2 | 64.9 Years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 12 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 5 Participants | 12 Participants | 19 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants by Degree of Bony Changes
Microscopic articular features including degree of bony changes were evaluated and scored (Normal, Sclerosis \[Lamellar/Mixed\], Subarticular Fracture/Collapse).
Time frame: Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months
Population: Arthroplasty analysis set: All participants who are enrolled in this study, have histological evaluation data and is based on the treatment received in their parent study (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants by Degree of Bony Changes | Sclerosis (Lamellar/Mixed) | 1 Participants |
| Placebo | Number of Participants by Degree of Bony Changes | Normal | 1 Participants |
| Placebo | Number of Participants by Degree of Bony Changes | Subarticular Fracture/Collapse | 0 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Bony Changes | Sclerosis (Lamellar/Mixed) | 2 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Bony Changes | Normal | 1 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Bony Changes | Subarticular Fracture/Collapse | 2 Participants |
| Fasinumab | Number of Participants by Degree of Bony Changes | Normal | 1 Participants |
| Fasinumab | Number of Participants by Degree of Bony Changes | Subarticular Fracture/Collapse | 5 Participants |
| Fasinumab | Number of Participants by Degree of Bony Changes | Sclerosis (Lamellar/Mixed) | 7 Participants |
Primary
Number of Participants by Degree of Cartilage Loss
Microscopic articular features including degree of cartilage were evaluated and scored (Superficial Fibrillation, Deep fissuring, Loss to Tide Mark, Loss to Exposed Bone).
Time frame: Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months
Population: Arthroplasty analysis set: All participants who are enrolled in this study, have histological evaluation data and is based on the treatment received in their parent study (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants by Degree of Cartilage Loss | Superficial Fibrillation | 0 Participants |
| Placebo | Number of Participants by Degree of Cartilage Loss | Deep fissuring | 1 Participants |
| Placebo | Number of Participants by Degree of Cartilage Loss | Loss to Tide Mark | 0 Participants |
| Placebo | Number of Participants by Degree of Cartilage Loss | Loss to Exposed Bone | 1 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Cartilage Loss | Loss to Exposed Bone | 3 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Cartilage Loss | Superficial Fibrillation | 1 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Cartilage Loss | Loss to Tide Mark | 1 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Cartilage Loss | Deep fissuring | 0 Participants |
| Fasinumab | Number of Participants by Degree of Cartilage Loss | Loss to Exposed Bone | 9 Participants |
| Fasinumab | Number of Participants by Degree of Cartilage Loss | Deep fissuring | 0 Participants |
| Fasinumab | Number of Participants by Degree of Cartilage Loss | Loss to Tide Mark | 2 Participants |
| Fasinumab | Number of Participants by Degree of Cartilage Loss | Superficial Fibrillation | 2 Participants |
Primary
Number of Participants by Degree of Synovial Lymphocytic Inflammation
Inflammatory cells including lymphocytes, mast cells, neutrophils, and eosinophils were scored by presence and degree (None present, Slight/Mild, Moderate, Marked/Band).
Time frame: Up to 24 weeks from the last dose of study drug in the parent study, an average of approximately 3 months
Population: Arthroplasty analysis set: All participants who are enrolled in this study, have histological evaluation data and is based on the treatment received in their parent study (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants by Degree of Synovial Lymphocytic Inflammation | None present | 0 Participants |
| Placebo | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Slight/Mild | 0 Participants |
| Placebo | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Moderate | 2 Participants |
| Placebo | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Marked/Band | 0 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Marked/Band | 0 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Synovial Lymphocytic Inflammation | None present | 2 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Moderate | 1 Participants |
| Non-steroidal Anti-inflammatory Drug (NSAID) | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Slight/Mild | 2 Participants |
| Fasinumab | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Marked/Band | 2 Participants |
| Fasinumab | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Slight/Mild | 5 Participants |
| Fasinumab | Number of Participants by Degree of Synovial Lymphocytic Inflammation | Moderate | 3 Participants |
| Fasinumab | Number of Participants by Degree of Synovial Lymphocytic Inflammation | None present | 3 Participants |