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

Symptomatic Knee Osteoarthritis Clinical Trial

Official title:

A Randomized, Two-arm, Placebo-controlled, Participant and Investigator-blinded Study Investigating the Efficacy, Safety and Tolerability of DFV890 in Patients With Symptomatic Knee Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04886258
• Other study ID #: CDFV890B12201
• Secondary ID: 2020-006104-17
• Status: Recruiting
• Phase: Phase 2
• Start date: September 20, 2021
• Est. completion date: April 7, 2025

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: April 7, 2025
• Est. primary completion date: March 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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) >=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 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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee
• Symptomatic Knee Osteoarthritis

Intervention

Drug:
• DFV890
DFV890
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Tucuman
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Novy Jicin
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 5
Czechia	Novartis Investigative Site	Uherske Hradiste
Germany	Novartis Investigative Site	Bad Doberan
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Wuerzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Kecskemet	Bacs Kiskun
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Tata	Komarom Esztergom
Hungary	Novartis Investigative Site	Veszprem
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Cluj Napoca	Cluj
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nove Mesto nad Vahom
Slovakia	Novartis Investigative Site	Piestany
Slovakia	Novartis Investigative Site	Rimavska Sobota
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Santiago De Compostela	A Coruna
Spain	Novartis Investigative Site	Sevilla
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Boston Univ School Of Medicine .	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Skylight Health Res Inc Color Spr Research	Colorado Springs	Colorado
United States	Novartis Investigative Site	Dallas	Texas
United States	TriWest Reserach Associates .	El Cajon	California
United States	Ctr for Adv Research and Education	Gainesville	Georgia
United States	Horizon Clinical Research	La Mesa	California
United States	Novartis Investigative Site	La Mesa	California
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Integral Rheumatology and Immunology Specialists IRIS	Plantation	Florida
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Czechia,  Germany,  Hungary,  Romania,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Knee injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale at week 12	To determine the efficacy of oral DFV890 vs. placebo in participants with knee OA for relieving OA pain	Baseline to Week 12
Secondary	Change from baseline in synovitis activity level measured from Ktrans by DCE-MRI at week 12	To assess the efficacy of DFV890 vs. placebo in participants with knee OA on inflammatory joint structure features	Baseline to Week 12
Secondary	Number of adverse events and serious adverse events	To assess the safety and tolerability of DFV890 vs. placebo	Up to Week 19 (end of study)
Secondary	Change from baseline in serum high sensitivity C-reactive protein level and absolute neutrophil counts at week 2,4,8 and 12	To assess the effect of DFV890 compared to placebo on systemic inflammatory status	Baseline to Week 12
Secondary	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	To assess the efficacy of DFV890 vs. placebo in improving participants' report of knee symptoms and associated problems over time	Week 2, 4, 8 and 12
Secondary	Change in KOOS pain subscale and NRS for pain from baseline to weeks 2, 4, 8 and 12	To assess the efficacy of DFV890 vs. placebo in relieving OA pain over time	Baseline to Week 2, 4, 8 and 12
Secondary	Pharmacokinetics of DFV890: Cmax	To assess pharmacokinetics of DFV890 in plasma	Week 2 and Week 12
Secondary	Pharmacokinetics of DFV890: AUC last	To assess pharmacokinetics of DFV890 in plasma	Week 2 and Week 12
Secondary	Pharmacokinetics of DFV890: AUC0-12h	To assess pharmacokinetics of DFV890 in plasma	Week 2 and Week 12
Secondary	Pharmacokinetics of DFV890: Ctrough	To assess pharmacokinetics of DFV890 in plasma	Week 2 and Week 12