A Proof-of-concept Study to Examine QUC398 in Participants With Knee OA

Study Overview
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Brief Summary
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The purpose of the study is to find out if the investigational treatment named QUC398 has beneficial effects on osteoarthritis knee pain and knee cartilage, and if it is safe and well tolerated.

Detailed Description
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This is a phase IIa study to establish the effect of QUC398 on pain and cartilage preservation in participants with symptomatic knee OA

Official Title
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A Randomized, Two-arm, Placebo-controlled, Participant, Investigator and Sponsor-blinded, Proof-of-concept Study Investigating the Efficacy, Safety and Tolerability of QUC398 in Patients With Symptomatic Knee Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: QUC398
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight ≥ 50 kg and body mass index 18 -35 kg/m2 at Screening 1 Kellgren-Lawrence grade 2 to 4 in the tibio-femoral compartment in the target knee confirmed by radiography in standing weight-bearing fixed flexion position and posterior-anterior view, at Screening 1 Radiographic medial joint space width (mJSW) of 2 to 4 mm in men or 1.5 to 3.5 mm in women measured at the X=0.225 fixed point location within the medial tibio-femoral compartment of the target knee at Screening 1 Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee for the majority of days in the last 3 months prior to Screening 1, as per participant's judgement Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee at Screening 1 and 2 . Moderate to severe OA pain (corresponding to Pain NRS ≥5 to ≤9) in the target knee during the last 7 days prior to Screening 3, confirmed by: Completed pain diary for at least 6 of the last 7 days prior to Screening 3, AND Diary reported Pain NRS ≥5 to ≤9 for at least 6 of the last 7 days prior to Screening 3 KOOS pain subscale ≤ 60 in the target knee at Screening 1, Screening 2, and Screening 3 Exclusion Criteria: Painful ipsilateral hip OA defined as a Pain NRS ≥3 on the majority of days in the last 3 months prior to Screening 1, as reported by the patient Symptomatic, patello-femoral pain in the target knee as per investigator's examination at Screening 1 Severe malalignment > 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1 Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI Previous exposure to any ADAMTS-5 drug, including QUC398. History or current diagnosis of ECG abnormalities Other protocol-defined inclusion/exclusion criteria may apply

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QUC398<br>QUC398 150 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to complete the 300 mg | Drug: QUC398<br>* QUC398 150 mg/mL, solution for s.c. injection (1 mL)<br>|
| Placebo Comparator: Placebo<br>Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding | Drug: Placebo<br>* Placebo 0 mg/mL, solution for s.c. injection (1 mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12 | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cartilage volume of the knee index region | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in preservation of cartilage in the medial compartment of the target knee | Week 52 | 
| Change from baseline in KOOS Pain subscale | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time | Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS) | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time | Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Change in Total KOOS | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving clinical symptoms and improving function in the target knee over time | Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Change in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time | Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS | Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time | Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QUC398, Osteoarthritis of Knee, Osteoarthritis of the Knee, Knee joint, Osteoarthritis