A Proof-of-concept Study to Examine QUC398 in Participants With Knee OA: Osteoarthritis, Knee... (2024)

Overview

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.

Full Title of Study: “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”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Triple (Participant, Care Provider, Investigator)
• Study Primary Completion Date: November 4, 2024

Detailed Description

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

Interventions

• Drug: QUC398
  • QUC398 150 mg/mL, solution for s.c. injection (1 mL)
• Drug: Placebo
  • Placebo 0 mg/mL, solution for s.c. injection (1 mL)

Arms, Groups and Cohorts

• Experimental: QUC398
  • QUC398 150 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to complete the 300 mg
• Placebo Comparator: Placebo
  • Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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 – mJSN 1-2 in the medial tibiofemoral compartment of the target knee, confirmed with Xray by central reader 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

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Novartis Pharmaceuticals
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals