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

Study Overview
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Brief Summary
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The study will determine the optimal dosing regimen of LNA043 in patients with knee osteoarthritis (OA).

Detailed Description
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This study is a 2-period, multicenter, randomized, parallel-group, double-blind, placebo-controlled study consisting of a 2-year Core period, followed by a 3 year extension period. The primary objective of this study is to assess the efficacy of LNA043 compared to placebo at Week 104 as measured by the mean change from baseline in cartilage thickness using qMRI of the target knee

Official Title
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A 5-year, Randomized, Double-blind, Placebo-controlled, Multi-center Study Assessing the Efficacy, Safety, and Tolerability of Intra-articular Regimens of LNA043 Versus Placebo in Patients With Symptomatic Knee Osteoarthritis

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: LNA043 Dosing Regimen A
* Drug: LNA043 Dosing Regimen B
* Drug: LNA043 Dosing Regimen C
* Drug: LNA043 Dosing Regimen D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 and other criteria as specified by the protocol 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 and other criteria as specified by the protocol

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LNA043 Dosing Regimen A<br>LNA043 injection to the knee with dosing regimen A | Drug: LNA043 Dosing Regimen A<br>* Injection to the knee<br>* Other names: LNA043;|
| Experimental: LNA043 Dosing Regimen B<br>LNA04 injection to the knee with dosing regimen B | Drug: LNA043 Dosing Regimen B<br>* Injection to the knee<br>* Other names: LNA043;|
| Experimental: LNA043 Dosing Regimen C<br>LNA043 injection to the knee with dosing regimen C | Drug: LNA043 Dosing Regimen C<br>* Injection to the knee<br>* Other names: LNA043;|
| Experimental: LNA043 Dosing Regimen D<br>LNA043 injection to the knee with dosing regimen D | Drug: LNA043 Dosing Regimen D<br>* Injection to the knee<br>* Other names: LNA043;|
| Placebo Comparator: Placebo<br>Injection to the knee | Drug: Placebo<br>* Injection to the knee<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the cartilage thickness of the medial compartment of the knee as assessed by imaging. | To evaluate cartilage thickness changes | Week 0 to Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain scale. The scale (5 questions) ranges from 0 to 50. Higher score indicates a worse outcome. | To evaluate changes from baseline in OA pain | Week 0 to Week 104 | 
| Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index function scale. The scale (17 questions) ranges from 0 to 170. Higher scores indicates a worse outcome. | To evaluate changes from baseline in physical function | Week 0 to Week 104 | 
| Change from baseline in the cartilage thickness of the knee as assessed by imaging. | To evaluate changes from baseline the cartilage structure | Week 0 to Week 104 | 
| Change from baseline in the Osteoarthritis Research Society International physical performance-based assessment of 40-meter (4×10m) fast-paced walk test | To evaluate changes from baseline in physical function | Week 0 to Week 104 | 
| Change from baseline in the Osteoarthritis Research Society International physical performance-based assessments 30-second chair stand test | To evaluate changes from baseline in physical function | Week 0 to Week 104 | 
| Change from baseline in the Osteoarthritis Research Society International physical performance-based assessment of 6-minute walking test | To evaluate changes from baseline in physical function | Weeek 0 to Week 104 | 
| Proportion of participants demonstrating structural progression | To evaluate structural progression | Week 0 to Week 104 | 
| Assessing percentage of participants with adverse events and serious adverse events | To evaluate safety and tolerability of the various LNA043 regimens | Week 0 to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LNA043, knee, arthritis, OA, knees