knee osteoarthritis MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: DFV890
Product Code: DFV890
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not yet established
Other descriptive name: DFV890
Concentration unit: mg milligram(s)
Concentra
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: • Male and female participants >= 50 and =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, as per participant's judgement • KOOS pain sub-scale score =7 with at least one region scoring 2) on contrast enhanced MRI (CE-MRI) of the whole knee for synovitis detection from 11 sites Please refer to protocol section 5.1 for an exhaustive list of inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: • Total WBC count 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: P.C.R. or antigen test against COVID-19 is mandatory where required by the local Health Authority and/or by local regulation, e.g. in Germany. Note that some countries may require P.C.R. testing only, e.g. Czech Republic.• Use of prohibited medications: any local i.a. treatment into the knee, including but not limited 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 from screening 1 ; systemic Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or selective 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 controlateral kneefor the majority of days in the last 3 months prior to Screening, as per patient judgment • 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 • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory assessments, in consultation with the Sponsor when necessary. Please refer to protocol section 5.2 for an exhaustive list of exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of oral DFV890 vs. placebo in participants with knee OA for relieving OA pain;Secondary Objective: 1) To assess the efficacy of DFV890 vs. placebo in participants with knee OA on inflammatory joint structure features 2) To assess the safety and tolerability of DFV890 vs. placebo 3) To assess the effect of DFV890 compared to placebo on systemic inflammatory status 4) To assess pharmacokinetics of DFV890 in plasma 5) To assess the efficacy of DFV890 vs. placebo in improving participants' report of knee symptoms and associated problems over time 6) To assess the efficacy of DFV890 vs. placebo in relieving OA pain over time;Primary end point(s): Change from baseline in Knee injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale at week 12 Time Frame: Baseline to Week 12;Timepoint(s) of evaluation of this end point: Time Frame: Baseline to Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Change from baseline in synovitis activity level measured from Ktrans by DCE-MRI at week 12 2) Systemic and local AEs and SAEs, ECGs parameters, Vital signs, Hematology, blood chemistry and urinalysis Time Frame: Up to the end of study 3) Change from baseline in serum high sensitivity C-reactive protein level and absolute neutrophil counts at week 2,4,8 and 12 Time Frame: Baseline to Week 12 4) Plasma samples to quantify concentrations of DFV890 at various time points (week 2 and week 12) and to derive PK parameters in plasma (including but not limited to Cmax, AUC last, AUC0-12h, and Cthrough) Time Frame: Week 2, Week 12 5) 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 Time Frame: Week 2, Week 4, Week 8, Week 12 6) Outcome Measure: Change in KOOS pain subscale and NRS for pain from baseline to weeks 2, 4, 8 and 12 Time Frame: Baseline to Week 2, 4, 8 and 12 ;Timepoint(s) of evaluation of this end point: 1) Time Frame: Baseline to Week 12 2) Time Frame: Up to the end of study 3) Time Frame: Baseline to Week 2, 4, 8 and 12 4) Time Frame: Week 2, Week 12 5) Time Frame: Week 2, Week 4, Week 8, Week 12 6) Time Frame: Baseline to Week 2, 4, 8 and 12 | — |
Countries
Argentina, Belgium, Czechia, Czech Republic, Germany, Hungary, Romania, Russian Federation, Slovakia, Spain, United States
Contacts
Public ContactInformacní služba – klin. hodnocení
Novartis s.r.o.
Outcome results
None listed