A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA)

Study Overview
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Brief Summary
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The study will establish safety and efficacy of canakinumab and LNA043 in patients with knee osteoarthritis (OA).

Official Title
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A Randomized, Four-arm, Canakinumab Placebo-controlled, Participant, Investigator and Sponsor-blinded Study Investigating the Safety, Tolerability and Efficacy of Intra-articular Canakinumab Followed by Intra-articular LNA043 in Patients With Knee Osteoarthritis

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: canakinumab
* Biological: LNA043
* Other: Placebo to canakinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe OA pain (corresponding to NRS Pain ≥5 to ≤9) in the target knee for the majority of days in the last 3 months prior to Screening KOOS pain subscale <60 for the target knee during Screening High sensitivity C-reactive Protein (hsCRP) ≥2 mg/L Radiographic KL grade 2 to 4 knee OA and joint space width (JSW) 2.0-4.0 mm (men) or 1.5-3.5 mm (women) in the medial tibiofemoral compartment (TFC) in the target knee Contrast-enhanced MRI (CE-MRI) diagnosed moderate or severe knee synovitis based on an established synovititis scoring system (moderate score 9-12 or severe score ≥13) Exclusion Criteria: History of, or planned; knee replacement (partial or total) in either knee; arthroscopy or lavage in either knee within 6 months prior to screening; any other previous surgical intervention in the target knee, or for the contralateral knee within 12 months prior to Screening, including mosaicplasty, microfracture, meniscectomy >50% or osteotomy Moderate to severe pain in the contralateral knee for the majority of days in the last 3 months prior to screening Malalignment >7.5° in the target knee (either varus or valgus) Any diagnosis of systemic inflammatory arthritis or connective tissue disease, including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, Paget's disease, systemic lupus erythematosus) or other systemic condition that might confound assessment of OA (e.g. fibromyalgia) Ipsilateral hip OA or hip prosthesis recently implanted (within 1 year prior to screening) or hip replacement on either side planned within the study period

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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<br>Placebo to canakinumab + LNA043 | Biological: LNA043<br>* intra-articular injection (into the knee)<br>Other: Placebo to canakinumab<br>* intra-articular injection (into the knee)<br>|
| Placebo Comparator: Placebo<br>Placebo to canakinumab | Other: Placebo to canakinumab<br>* intra-articular injection (into the knee)<br>|
| Experimental: canakinumab + LNA043<br>canakinumab + LNA043 | Biological: canakinumab<br>* intra-articular injection (into the knee)<br>* Other names: ACZ885;Biological: LNA043<br>* intra-articular injection (into the knee)<br>|
| Experimental: canakinumab<br>canakinumab | Biological: canakinumab<br>* intra-articular injection (into the knee)<br>* Other names: ACZ885;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cartilage volume in the index region measured by MRI | Comparing LNA043 with no LNA043 treatment (Placebo) arms. | Baseline to Day 197 | 
| Change in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale | Comparing canakinumab with no canakinumab treatment (Placebo) arms. The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems. | Baseline to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-LNA043 antibodies in serum |  | Day 15, 43, 85, 197 and 365 | 
| ANGPTL3 serum concentrations |  | Day 1, 15, 43, 85, 197 and 365 | 
| ANGPTL3 synovial fluid concentrations |  | Day 1, 15, 43 and 71 | 
| LNA043 PK profile in serum (Cmax) |  | Day 1 and 43 | 
| LNA043 PK profile in serum (Tmax) |  | Day 1 and 43 | 
| LNA043 PK profile in serum (AUC) |  | Day 1 and 43 | 
| Change in cartilage volume of the index region measured by MRI |  | Baseline to Day 197 and 365 | 
| Change in cartilage thickness of the index region measured by MRI |  | Baseline to Day 197 and 365 | 
| Change in synovitis level measured from Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI) |  | Baseline to Day 85 | 
| Change in numeric rating scale (NRS) Pain over time | The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. The scale ranges from 0 (no pain) to 10 (worst possible pain). | Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 | 
| Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale over time | The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems. | Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 | 
| Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in daily living (ADL) subscale over time | The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales: Pain (9 questions), Symptoms (7 questions), Function in daily living (ADL) (17 questions), Function in sport and recreation (Sport/Rec) (5 questions) and knee related Quality of Life (QoL) (4 questions). On this scale, 100% indicates no problems and 0% indicates extreme problems. | Baseline to Day 15, 29, 43, 57, 71, 85, 197 and 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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canakinumab, LNA043, knee, osteoarthritis, OA, joint pain, cartilage, MRI, DCE-MRI, KOOS, NRS Pain, IPAQ