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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
* 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

• Tampa, Florida, United States
• Boston, Massachusetts, United States
• Morehead City, North Carolina, United States
• Southport, Queensland, Australia
• Christchurch, Australia
• St Leonards, Australia
• Herlev, Denmark
• Vejle, Denmark
• Nice, France
• Orléans, France
• Sabadell, Barcelona, Spain
• Leganés, Madrid, Spain
• A Coruña, Spain
• Seville, Spain