Study of efficacy, safety and tolerability of DFV890 in patients with knee osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

9 Nov 2021 → 23 Dec 2024

Decision date (initial)

2024-06-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-507559-30-00

EudraCT number

2020-006104-17

ClinicalTrials.gov

NCT04886258

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacogenetic, Safety, Therapy, Pharmacodynamic

To determine the efficacy of DFV890 versus placebo in participants with knee Osteoarthritis (OA) for relieving pain, based on change from baseline to week 12 in the knee injury and osteoarthritis outcome score (KOOS) pain sub-scale.

Secondary objectives 6

1. To assess the efficacy of treatment with DFV890 versus placebo in participants with knee OA on inflammatory joint structure features based on change from baseline in synovitis activity level measured by Volume transfer constant (K-trans) by Magnetic Resonance Imaging (MRI) at week 12.
2. To evaluate the safety and tolerability of DFV890 compared to placebo over the course of the study based on systemic and local adverse events and serious adverse events; electrocardiograms; vital signs; hematology, blood chemistry and urinalysis.
3. To evaluate the change in systemic inflammatory markers (serum high sensitivity C-reactive protein level and absolute neutrophil count), when treated with DFV890 compared to placebo after 2, 4, 8 and 12 weeks of treatment.
4. To evaluate the plasma pharmacokinetics of DFV890 after 2 and 12 weeks of treatment.
5. To evaluate changes in knee symptoms and associated parameters, when treated with DFV890 compared to placebo after 2, 4, 8 and 12 weeks of treatment based on KOOS sub-scales including other symptoms, function in daily living, function in sport and recreation, knee-related quality of life.
6. To evaluate the efficacy of DFV890 compared to placebo in relieving OA pain over time based on change in KOOS pain subscale from baseline to weeks 2, 4, 8 and 12 weeks, and on change in Numeric Rating Scale (NRS) for pain from baseline to weeks 2, 4, 8 and 12.

Conditions and MedDRA coding

Knee Osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male and female participants >= 50 and <= 80 years old on the day of Informed Consent signature.
2. 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
3. High sensitivity C-reactive protein (hsCRP) >=1.8 mg/L at screening
4. Symptomatic OA with pain (Numeric Rating Scale [NRS] 5-9, inclusive) in the target knee for the majority of days in the last 3 months prior to screening.
5. KOOS pain sub-scale score <= 60 in index knee at screening and baseline
6. Radiographic disease: K&L grade 2 or 3 knee osteoarthritis in the target knee
7. Active synovial inflammation at screening, (defined as summary 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

Exclusion criteria 7

1. 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
2. Known autoimmune disease with inflammatory arthritides (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystal-induced arthritides (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
3. 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: Polymerase Chain Reaction (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.
4. 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 repair from 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.
5. 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
6. Severe malalignment greater than 7.5 degrees in the target knee (either varus or valgus), measured using x-ray at Screening.
7. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in Knee injury and Osteoarthritis Outcome Score (KOOS) pain sub-scale at week 12

Secondary endpoints 7

1. Change from baseline in synovitis activity level measured from K-trans by DCE-MRI at week 12
2. Systemic and local Adverse Events and Serious Adverse Events, Electrocardiograms (ECGs) parameters, Vital signs, Hematology, blood chemistry and urinalysis.
3. Change from baseline in serum high sensitivity C-reactive protein level and absolute neutrophil counts at week 2,4,8 and 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)
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
6. Change in KOOS pain subscale from baseline to weeks 2, 4, 8 and 12
7. Change in numeric rating scale (NRS) for pain from baseline to weeks 2, 4, 8 and 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 20

Locations

5 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications