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

Phase 2

Terminated

• Conditions: Osteoarthritis, Knee
• Interventions: Drug: QUC398; Drug: Placebo

• Registration Number: NCT05462990
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2022-07-14
• Study First Submitted QC: 2022-07-14
• Study First Posted: 2022-07-18
• Study Start: 2022-11-09
• Primary Completion: 2024-08-02
• Status Verified: 2025-04
• Study Completion: 2025-04-08
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 101

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QUC398	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	Placebo	Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Cartilage volume of the knee index region	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 Patient's Global Assessment (PGA) as assessed by NRS	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 pain assessed by a Pain Numerical Rating Scale (NRS)	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	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	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 KOOS Pain subscale	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

Trial Locations

Locations (4)

Clinical Research of West Florida Inc; 🇺🇸 Tampa, Florida, United States

Boston Univ School Of Medicine; 🇺🇸 Boston, Massachusetts, United States

West Clinical Research; 🇺🇸 Morehead City, North Carolina, United States

Novartis Investigative Site; 🇪🇸 Sevilla, Spain