Clinical trial NCT04886258: Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Symptomatic Knee Osteoarthritis
Keywords: Osteoarthritis
Knee osteoarthritis
DFV890
Adult
NLRP3 inhibitor
Inflammasome inhibition
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-05-14
Enrollment: 115
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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) \>=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

Primary outcomes:
measure: Change from baseline in Knee injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale at week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change from baseline in synovitis activity level measured from Ktrans by DCE-MRI at week 12
timeFrame: Baseline to Week 12
measure: Number of adverse events and serious adverse events
timeFrame: Up to Week 19 (end of study)
measure: Change from baseline in serum high sensitivity C-reactive protein level and absolute neutrophil counts at week 2,4,8 and 12
timeFrame: Baseline to Week 12
measure: 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
timeFrame: Week 2, 4, 8 and 12
measure: Change in KOOS pain subscale and NRS for pain from baseline to weeks 2, 4, 8 and 12
timeFrame: Baseline to Week 2, 4, 8 and 12
measure: Pharmacokinetics of DFV890: Cmax
timeFrame: Week 2 and Week 12
measure: Pharmacokinetics of DFV890: AUC last
timeFrame: Week 2 and Week 12
measure: Pharmacokinetics of DFV890: AUC0-12h
timeFrame: Week 2 and Week 12
measure: Pharmacokinetics of DFV890: Ctrough
timeFrame: Week 2 and Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: ARENSIA Explor Med Res Clinic
state: Arizona
city: El Cajon
country: United States
facility: TriWest Reserach Associates
state: California
city: Colorado Springs
country: United States
facility: Skylight Health Res Inc Color Spr
state: Colorado
city: Plantation
country: United States
facility: IRIS Research and Development
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Gainesville
country: United States
facility: Ctr for Adv Research and Education
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Novy Jicin
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Bad Doberan
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Kecskemet
country: Hungary
facility: Novartis Investigative Site
state: Bacs Kiskun
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Miskolc
country: Hungary
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
state: Cluj
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Nove Mesto nad Vahom
country: Slovakia
facility: Novartis Investigative Site
city: Piestany
country: Slovakia
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
Study officials:
References: