Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis (ONWARDS)

Novartis

Status and phase: Terminated; Phase 2

Conditions: Osteoarthritis

Treatments: Drug: Placebo; Drug: LNA043

Study type: Interventional

Funder types: Industry

Identifiers

NCT04864392

2023-509937-37-00 (Registry Identifier)

CLNA043A12202

2020-004897-22 (EudraCT Number)

Details and patient eligibility

About

This was a multicenter, randomized, double-blind, placebo-controlled Phase IIb study evaluating intra-articular LNA043 in patients with knee osteoarthritis.

Full description

The study was structured as a two-period design:

• A 2-year Core Period, followed by
• A 3-year Extension Period, consisting of 2 years of continued treatment and 1 year of follow-up, totaling 5 years.

Participants were randomized in a 1:1:1:1:1 ratio into five treatment arms:

• LNA043 20 mg Q4w ×3, repeated every 6 months.
• LNA043 40 mg ×1 and placebo Q4w ×2, repeated every 6 months.
• LNA043 40 mg Q4w ×3 followed six months later by placebo Q4w ×3, repeated every 12 months.
• LNA043 40 mg Q4w ×3, repeated every 6 months.
• Placebo Q4w ×3, repeated every 6 months.

All injections were administered intra-articularly (i.a.) to the target knee. Placebo injections (saline solution) were used throughout the study to maintain blinding and ensure consistency in injection frequency across arms.

During the Extension Period:

• Participants from the 6-month cycle arms continued with a single injection of the same LNA043 dose every 6 months.
• Participants from the 12-month cycle arm received LNA043 40 mg every 12 months and placebo every other 6 months.
• Participants who received placebo during the Core Period continued with a single injection of the same placebo every 6 months.

The final year of the Extension Period was a no-treatment follow-up phase for all participants.

The study was terminated early following the Week 104 primary endpoint analysis due to lack of effect.There was no safety related reasons for early termination or safety concerns for the subjects in the study.

Enrollment: 576 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Males and females between 40 and 75 years of age
• Body mass index (BMI) < 40 kg/m2
• Diagnosis of primary tibiofemoral knee OA by standard American College of Rheumatology clinical and radiographic criteria

Key Exclusion Criteria:

• Participants with radiographic knee OA K-L grade = 4 on the non-target knee
• Arthroscopy of the target knee within the 6 months prior to Screening
• Hemoglobin < 8.5 g/dL (85 g/L) or platelet count < 100,000/μL

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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576 participants in 5 patient groups, including a placebo group

Arm 1: LNA043 40 mg Q4W x3, Q6m

Experimental group

Description:

Core Period: Three i.a. injections of LNA043 40 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.

Treatment:

Drug: LNA043

Arm 2: LNA043 40 mg Q4W x3, Q12m

Experimental group

Description:

Core Period: Three i.a. injections of LNA043 40 mg (Q4W ×3), followed six months later by three placebo injections (Q4W ×3). Extension Period: One i.a. injection of LNA043 40 mg every 12 months for 2 years, with a placebo injection administered six months after each LNA043 dose to maintain blinding.

Treatment:

Drug: LNA043

Drug: Placebo

Arm 3: LNA043 20 mg Q4W x3, Q6m

Experimental group

Description:

Core Period: Three i.a. injections of LNA043 20 mg, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 20 mg every 6 months for 2 years.

Treatment:

Drug: LNA043

Arm 4: LNA043 40 mg x1, Q6m

Experimental group

Description:

Core Period: One i.a. injection of LNA043 40 mg, followed by two placebo injections (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of LNA043 40 mg every 6 months for 2 years.

Treatment:

Drug: LNA043

Drug: Placebo

Placebo

Placebo Comparator group

Description:

Core Period: Three i.a. injections of placebo, administered once every 4 weeks (Q4W ×3), repeated every 6 months. Extension Period: One i.a. injection of placebo every 6 months for 2 years.

Treatment:

Drug: Placebo