Clinical Trials Register (2024)

E.1 Medical condition or disease under investigationE.1.1Medical condition(s) being investigated

Knee osteoarthritis

E.1.1.1Medical condition in easily understood language

Knee osteoarthritis

E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]MedDRA ClassificationE.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3Condition being studied is a rare disease No E.2 Objective of the trialE.2.1Main objective of the trial

To assess efficacy of QUC398 vs placebo in relieving OA pain in the target knee

E.2.2Secondary objectives of the trial

•To assess the efficacy of QUC398 vs placebo in preservation of cartilage in the medial compartment of the target knee
•To assess the efficacy of QUC398 vs placebo in relieving OA pain in the target knee over time
•To assess the efficacy of QUC398 vs placebo in relieving clinical symptoms and improving function in the target knee over time
•To assess the safety and tolerability of QUC398 vs placebo.

E.2.3Trial contains a sub-study No E.3Principal inclusion criteria

•Weight ≥ 50 kg and a body mass index (BMI) between 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 narrowing (mJSN) 1-2 within the medial tibio-femoral compartment of the target knee, confirmed by Xray 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.

Additional protocol specified criteria may apply.

E.4Principal 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 relevant cardiovascular diseases and ECG abnormalities.

Additional protocol specified criteria may apply.

E.5 End pointsE.5.1Primary end point(s)

Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12

E.5.1.1Timepoint(s) of evaluation of this end point

Week 12

E.5.2Secondary end point(s)

•Change from baseline in cartilage volume of the knee index region at Week 52, as determined from the automated segmentation of 3D-MRI scans
•Change from baseline in KOOS Pain subscale at 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) at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
•Change from baseline in total KOOS at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
•Change from baseline in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life at 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 at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
•Systemic and local Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, Electrocardiogram parameters (ECGs), Vital signs, Laboratory tests

E.5.2.1Timepoint(s) of evaluation of this end point

As specified in the secondary endpoints

E.6 and E.7 Scope of the trialE.6Scope of the trialE.6.1Diagnosis No E.6.2Prophylaxis No E.6.3Therapy No E.6.4Safety Yes E.6.5Efficacy Yes E.6.6Pharmaco*kinetic Yes E.6.7Pharmacodynamic Yes E.6.8Bioequivalence No E.6.9Dose response No E.6.10Pharmacogenetic Yes E.6.11Pharmacogenomic No E.6.12Pharmacoeconomic No E.6.13Others Yes E.6.13.1Other scope of the trial description

Tolerability

E.7Trial type and phaseE.7.1Human pharmacology (Phase I) No E.7.1.1First administration to humans No E.7.1.2Bioequivalence study No E.7.1.3Other No E.7.1.3.1Other trial type descriptionE.7.2Therapeutic exploratory (Phase II) Yes E.7.3Therapeutic confirmatory (Phase III) No E.7.4Therapeutic use (Phase IV) No E.8 Design of the trialE.8.1Controlled Yes E.8.1.1Randomised Yes E.8.1.2Open No E.8.1.3Single blind No E.8.1.4Double blind Yes E.8.1.5Parallel group Yes E.8.1.6Cross over No E.8.1.7Other No E.8.2 Comparator of controlled trialE.8.2.1Other medicinal product(s) No E.8.2.2Placebo Yes E.8.2.3Other No E.8.2.4Number of treatment arms in the trial2E.8.3 The trial involves single site in the Member State concerned No E.8.4 The trial involves multiple sites in the Member State concerned Yes E.8.4.1Number of sites anticipated in Member State concerned2E.8.5The trial involves multiple Member States Yes E.8.5.1Number of sites anticipated in the EEA14E.8.6 Trial involving sites outside the EEAE.8.6.1Trial being conducted both within and outside the EEA Yes E.8.6.2Trial being conducted completely outside of the EEA No E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

New Zealand

Australia

United States

Denmark

France

Norway

Spain

E.8.7Trial has a data monitoring committee No E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Study completion is defined as when the last participant finishes their End of study (EOS) visit.

E.8.9 Initial estimate of the duration of the trialE.8.9.1In the Member State concerned years2E.8.9.1In the Member State concerned months8E.8.9.1In the Member State concerned days3E.8.9.2In all countries concerned by the trial years2E.8.9.2In all countries concerned by the trial months11