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

Inclusion Criteria:

1. Weight ≥ 50 kg and body mass index 18 -35 kg/m2 at Screening 1
2. 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
3. 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
4. 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:

1. 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
2. Symptomatic, patello-femoral pain in the target knee as per investigator's examination at Screening 1
3. Severe malalignment > 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1
4. Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI
5. Previous exposure to any ADAMTS-5 drug, including QUC398.
6. History or current diagnosis of ECG abnormalities

Other protocol-defined inclusion/exclusion criteria may apply