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

NCT04886258 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CDFV890B122012020-006104-17
• Study Type: interventional
• Target: 115
• Locations: 8 countries
• Sites: 31

Brief Summary

This was a double-blinded, two-arm, phase 2a study to assess efficacy, safety and tolerability of DFV890 in participants with symptomatic knee osteoarthritis.

Conditions

Symptomatic Knee Osteoarthritis

Keywords

Osteoarthritis; Knee osteoarthritis; DFV890; Adult; NLRP3 inhibitor; Inflammasome inhibition

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale

  The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the pain frequency/severity during functional activities consisting of 9 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no pain and 0 indicating extreme pain) is calculated for each subscale. Change from baseline in KOOS pain score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint, baseline-by-timepoints interaction and treatment-by-timepoints interaction as fixed effects. Missing data is assumed to be Missing at Random (MAR).

  Baseline, Week 12

Secondary Outcomes (13)

• Change From Baseline in Synovitis Activity Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI)

  Baseline, Week 12

• Change From Baseline in Serum High Sensitivity C-reactive Protein (hsCRP) Level

  Baseline, Weeks 2, 4, 8 and 12

• Change From Baseline in Absolute Neutrophil Counts (ANC)

  Baseline, Weeks 2, 4, 8 and 12

• Maximum Plasma Concentration (Cmax) of DFV890

  Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h

• Area Under Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of DFV890

  Week 2 and Week 12: pre-dose, 1h, 3h, 5h, 8h

Study Arms (2)

DFV890

EXPERIMENTAL

DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.

Drug: DFV890

Placebo

PLACEBO COMPARATOR

Matching Placebo was administered orally twice per day during 12 weeks.

Drug: Placebo

Interventions

DFV890 DRUG

DFV890 was administered orally twice per day, 10 mg during 2 weeks and 25 mg during the next 10 weeks.

DFV890

Placebo DRUG

Matching Placebo was administered orally twice per day during 12 weeks.

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

ARENSIA Explor Med Res Clinic

Phoenix, Arizona, 85015, United States

Location

TriWest Reserach Associates

El Cajon, California, 92020, United States

Location

Skylight Health Res Inc Color Spr

Colorado Springs, Colorado, 80917, United States

Location

IRIS Research and Development

Plantation, Florida, 33324, United States

Location

Conquest Research

Winter Park, Florida, 32789, United States

Location

Ctr for Adv Research and Education

Gainesville, Georgia, 30501, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1181ACH, Argentina

Location

Novartis Investigative Site

San Miguel, Tucumán Province, T4000CBC, Argentina

Location

Novartis Investigative Site

San Miguel de Tucumán, 4000, Argentina

Location

Novartis Investigative Site

Brno, Czech Republic, 66250, Czechia

Location

Novartis Investigative Site

Nový Jičín, 741 01, Czechia

Location

Novartis Investigative Site

Prague, 150 06, Czechia

Location

Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

Location

Novartis Investigative Site

Bad Doberan, 18209, Germany

Location

Novartis Investigative Site

Berlin, 10787, Germany

Location

Novartis Investigative Site

Hamburg, 22143, Germany

Location

Novartis Investigative Site

Hamburg, 22415, Germany

Location

Novartis Investigative Site

Leipzig, 04107, Germany

Location

Novartis Investigative Site

Kecskemét, Bács-Kiskun county, 6044, Hungary

Location

Novartis Investigative Site

Budapest, 1027, Hungary

Location

Novartis Investigative Site

Miskolc, 3526, Hungary

Location

Novartis Investigative Site

Veszprém, 8200, Hungary

Location

Novartis Investigative Site

Cluj-Napoca, Cluj, 400006, Romania

Location

Novartis Investigative Site

Bucharest, 011658, Romania

Location

Novartis Investigative Site

Nové Mesto nad Váhom, 915 01, Slovakia

Location

Novartis Investigative Site

Piešťany, 921 01, Slovakia

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

A Coruña, 15006, Spain

Location

Novartis Investigative Site

Seville, 41010, Spain

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Osteoarthritis; Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

Due to MedDRA version 27.1, the reported term 'interstitial pneumonia' was decoded to the Preferred Term 'interstitial lung disease' in the Adverse Events report.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 14, 2021
• Study Start: September 20, 2021
• Primary Completion: December 14, 2024
• Study Completion: December 23, 2024
• Last Updated: March 31, 2026
• Results First Posted: January 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

SL (2); ES (4); DE (5); RO (2); CZ (4); US (7); AR (3); HU (4)