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

Phase 2

Active, not recruiting

• Conditions: Symptomatic Knee Osteoarthritis
• Interventions: Drug: Placebo; Drug: DFV890

• Registration Number: NCT04886258
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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 21 weeks.

Detailed Description

The purpose of the Phase 2a proof of concept study is to evaluate the safety and tolerability of DFV890 in participants with symptomatic knee OA, and to determine the efficacy of DFV890 in reducing knee pain as evidenced by change in KOOS (knee injury and osteoarthritis outcome score).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-05-10
• Study First Submitted QC: 2021-05-10
• Study First Posted: 2021-05-14
• Study Start: 2021-09-20
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-05
• Last Update Posted: 2024-10-08
• Primary Completion: 2024-12-11
• Study Completion: 2024-12-27

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 115

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) >=1.8 mg/L at screening
• Symptomatic OA with pain (corresponding to 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 in the target knee, confirmed by X-ray at screening.
• Active synovial inflammation at screening (defined a summary score of ≥7 with at least one region scoring 2) on contrast enhanced MRI (CE-MRI) of the whole knee for synovitis detection from 11 sites.

Key

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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.a. 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 repairfrom screening 1; systemic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), selective Cyclooxygenase-2 (COX- 2) inhibitors or other non-opioid analgesics not defined as basic pain medication 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.
• Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to Screening, as per patient judgment.
• Severe malalignment greater than 7.5 degrees in the target knee (either varus or valgus), measured using x-ray at Screening

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
DFV890	DFV890	DFV890

Primary Outcome Measures

Name	Time	Method
Change from baseline in Knee injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale at week 12	Baseline to Week 12	To determine the efficacy of oral DFV890 vs. placebo in participants with knee OA for relieving OA pain

Secondary Outcome Measures

Name	Time	Method
Change from baseline in synovitis activity level measured from Ktrans by DCE-MRI at week 12	Baseline to Week 12	To assess the efficacy of DFV890 vs. placebo in participants with knee OA on inflammatory joint structure features
Change from baseline in serum high sensitivity C-reactive protein level and absolute neutrophil counts at week 2,4,8 and 12	Baseline to Week 12	To assess the effect of DFV890 compared to placebo on systemic inflammatory status
Change from baseline in KOOS sub-scales (other symptoms, function in daily living, function in sport and recreation, knee-related quality of life) at weeks 2, 4, 8 and 12	Week 2, 4, 8 and 12	To assess the efficacy of DFV890 vs. placebo in improving participants' report of knee symptoms and associated problems over time
Pharmacokinetics of DFV890: Cmax	Week 2 and Week 12	To assess pharmacokinetics of DFV890 in plasma
Pharmacokinetics of DFV890: AUC last	Week 2 and Week 12	To assess pharmacokinetics of DFV890 in plasma
Pharmacokinetics of DFV890: AUC0-12h	Week 2 and Week 12	To assess pharmacokinetics of DFV890 in plasma
Pharmacokinetics of DFV890: Ctrough	Week 2 and Week 12	To assess pharmacokinetics of DFV890 in plasma
Number of adverse events and serious adverse events	Up to Week 19 (end of study)	To assess the safety and tolerability of DFV890 vs. placebo
Change in KOOS pain subscale and NRS for pain from baseline to weeks 2, 4, 8 and 12	Baseline to Week 2, 4, 8 and 12	To assess the efficacy of DFV890 vs. placebo in relieving OA pain over time

Trial Locations

Locations (10)

TriWest Reserach Associates .; 🇺🇸 El Cajon, California, United States

ARENSIA Explor Med Res Clinic Research; 🇺🇸 Phoenix, Arizona, United States

Horizon Clinical Research; 🇺🇸 La Mesa, California, United States

Skylight Health Res Inc Color Spr Research; 🇺🇸 Colorado Springs, Colorado, United States

Skylight Health Res Inc Color Spr; 🇺🇸 Colorado Springs, Colorado, United States

Integral Rheumatology and Immunology Specialists IRIS; 🇺🇸 Plantation, Florida, United States

Conquest Research; 🇺🇸 Winter Park, Florida, United States

Ctr for Adv Research and Education; 🇺🇸 Gainesville, Georgia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Novartis Investigative Site; 🇪🇸 Sevilla, Spain