Study to Evaluate Arthroplasty Specimens for Osteoarthritis of the Knee and Hip

• Fasinumab (Drug), also known as REGN475: 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
• Naproxen (Drug): 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
• Diclofenac (Drug), also known as ZORVOLEX: 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
• Celecoxib (Drug), also known as CELEBREX: 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
• Placebo (Drug): 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

Primary outcomes

• 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).

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Number of Participants by Degree of Synovial Lymphocytic Inflammation (Primary), Count of participants, Participants: Placebo 0; Non-steroidal Anti-inflammatory Drug (NSAID) 2; Fasinumab 3
• Number of Participants by Degree of Cartilage Loss (Primary), Count of participants, Participants: Placebo 0; Non-steroidal Anti-inflammatory Drug (NSAID) 1; Fasinumab 2
• Number of Participants by Degree of Bony Changes (Primary), Count of participants, Participants: Placebo 1; Non-steroidal Anti-inflammatory Drug (NSAID) 1; Fasinumab 1

Adverse events

Time frame: Safety was not analyzed or collected specifically for this sub-study

Limitations and caveats: The study was anticipated to close in Feb 2021, but ended prematurely on 25 Aug 2020 (date of global last arthroplasty surgery for last subject enrolled) due to lack of enrollment.

• Study Protocol (PDF, 2018-07-11)
• Statistical Analysis Plan (PDF, 2020-11-23)

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals

NIH grants: 2018