Overview

Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis

Status:
Recruiting
Trial end date:
2023-02-14
Target enrollment:
0
Participant gender:
All
Summary
This is a double-blinded, two-arm, phase II study to assess efficacy, safety and tolerability of DFV890 in participants with symptomatic knee osteoarthritis. The study includes a screening period, a treatment period and a follow-up period. At most, the study duration is 19 weeks.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Novartis Pharmaceuticals
Criteria
Key Inclusion Criteria:

- Male and female participants >= 50 and <= 80 years old on the day of Informed Consent
signature.

- Participants must weigh at least 50 kg to participate in the study, and must have a
body mass index (BMI) within the range of 18 - 35 kg/m2 at screening. BMI = Body
weight (kg) / [Height (m)]2

- High sensitivity C-reactive protein (hsCRP) >=2 mg/L at screening

- Symptomatic OA with pain (Numeric Rating Scale [NRS] 5-9, inclusive) in the target
knee for the majority of days in the last 3 months prior to screening

- KOOS pain sub-scale score <= 60 in index knee at screening and baseline

- Radiographic disease: K&L grade 2 or 3 knee osteoarthritis and joint space width 2-4
mm for males and 1.5-3.5 mm for females in the medial tibiofemoral compartment (TFC)
in the target knee

- Active synovial inflammation at screening, defined as either moderate (score 9-12) or
severe (score >=13) based on contrast enhanced MRI (CE-MRI) of the whole knee for
synovitis detection from 11 sites

Key Exclusion Criteria:

- Total WBC count < 3,000/µL, absolute peripheral blood neutrophil count (ANC) <
1,000/µL, hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/µL at Screening

- Known autoimmune disease with inflammatory arthritis (including but not limited to
rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus
erythematosus), crystal-induced arthritis (gout, pseudogout associated arthritis),
active acute or chronic infection or past infection of the knee joint, Lyme disease
involving the knee, reactive arthritis, systemic cartilage disorders, moderate to
severe fibromyalgia (widespread pain index, WPI, >4 out of 19), or a known systemic
connective tissue disease

- Any known active infections, including skin or knee infections or infections that may
compromise the immune system, such as HIV or chronic hepatitis B or C infection.
COVID-19 specific: PCR or antigen test against COVID-19 is mandatory where required by
the local Health Authority and/or by local regulation, e.g. in Germany.

- Use of prohibited medications: any local i.e. treatment into the knee, including but
not restricted to viscosupplementation and corticosteroids within 12 weeks prior to
Day 1; long-term treatment (>14 days) with oral corticosteroids >5 mg/day within 4
weeks prior to Day 1; oral glucosamine, chondroitin sulfate, or any nutraceutical with
potential activity on cartilage repair within 2 weeks prior to Day 1; systemic
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or selective COX-2 inhibitors within 5
half-lives from PRO assessments; any other immunomodulatory drugs or treatment which
cannot be discontinued or switched to a different medication within 28 days or 5
half-lives of screening (whichever is longer if required by local regulations), or
until the expected PD effect has returned to baseline.

- Contralateral knee pain >=4 by NRS for the majority of days in the last 3 months prior
to Screening

- Participants with the CYP2C9 *3/*3 genotype defined as homozygous carriers of the
CYP2C9*3 allele.

- Severe malalignment greater than 7.5 degrees in the target knee (either varus or
valgus), measured using x-ray at Screening