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

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

The purpose of the study was to find out if the investigational treatment named QUC398 had beneficial effects on osteoarthritis (OA) knee pain and knee cartilage, and if it was safe and tolerated.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: QUC398; Drug: Placebo

Detailed Description

This was a non-confirmatory study using a randomized, placebo-controlled, parallel-group, participant, investigator and sponsor-blinded design to investigate efficacy, safety and tolerability of subcutaneous injections of QUC398 300 mg vs placebo every 4 weeks (q4w) in participants with symptomatic knee OA.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Christchurch, Australia, 8011
    • Novartis Investigative Site
  • St Leonards, Australia, 2065
    • Novartis Investigative Site
  • Queensland
    • Southport, Queensland, Australia, 4222
      • Novartis Investigative Site
• Denmark
  • Herlev, Denmark, 2730
    • Novartis Investigative Site
  • Vejle, Denmark, 7100
    • Novartis Investigative Site
• France
  • Nice, France, 06001
    • Novartis Investigative Site
  • Orléans, France, 45100
    • Novartis Investigative Site
• Spain
  • A Coruña, Spain, 15006
    • Novartis Investigative Site
  • Seville, Spain, 41010
    • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Madrid
    • Leganés, Madrid, Spain, 28915
      • Novartis Investigative Site
• United States
  • Florida
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida Inc
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Univ School of Medicine
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • West Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QUC398 300 mg; QUC398 was administered subcutaneous every 4 weeks during 48 weeks.	Drug: QUC398; QUC398 150 mg/mL, solution for subcutaneous (s.c) injection (1 mL). 2 injections were administered to complete 300 mg.
Placebo Comparator: Placebo; Placebo was administered subcutaneous every 4 weeks during 48 weeks.	Drug: Placebo; Matching Placebo solution for s.c. injection (1 mL). 2 injections were administered per dose to ensure blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale at Week 12	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the pain frequency/severity during functional activities consisting of 9 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. Change from baseline in KOOS pain score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on a primary estimand framework.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cartilage Volume of the Knee Index Region Measured by 3D-MRI	Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee. Change from baseline in cartilage volume was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-timepoints as fixed effects, and participant as random effect. Missing data is assumed to be Missing at Random (MAR). Based on a secondary estimand framework.	Baseline, Week 52
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the pain frequency/severity during functional activities consisting of 9 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A positive change from baseline indicates an improvement. Change from baseline in KOOS pain score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Pain Assessed by a Pain Numerical Rating Scale (NRS)	The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. NRS pain score ranges from 0-10 and for analyses were transformed to a 0-100 scale to be consistent with KOOS pain scores. A negative change from baseline implied improvement in pain. The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst. Change from baseline in NRS pain score was analyzed using a MMRM including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Total Knee Injury and Osteoarthritis Outcome Score (KOOS)	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems.The original KOOS consists of 5 subscales: Pain, other Symptoms (like stiffness and swelling), Function in Daily Living, Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. Total KOOS scale was calculated as the average of all subscales (100 indicating no symptoms and 0 indicating extreme symptoms). A positive change from baseline indicates an improvement. Change from baseline in KOOS total score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Other Symptoms Subscale	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is other symptoms (eg., stiffness, swelling, clicking) consisting of 7 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A positive change from baseline indicates an improvement. Change from baseline in KOOS Other symptoms score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living Subscale	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the Function in Daily Living consisting of 17 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A positive change from baseline indicates an improvement. Change from baseline in KOOS Function in daily living score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Sport and Recreation Subscale	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the function in sport and recreation consisting of 5 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A positive change from baseline indicates an improvement. Change from baseline in KOOS Function in sport and recreation score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Knee Related Quality of Life Subscale	The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the knee-related quality of life consisting of 4 questions with a recall of 7 days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A positive change from baseline indicates an improvement. Change from baseline in KOOS Knee related quality of life score was analyzed using a mixed effects model for repeated measures (MMRM) including all time-points to compare treatment groups. The model includes baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing at Random (MAR). Based on second secondary estimand framework.	Baseline, 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	The PGA of osteoarthritis disease activity was performed using a NRS (11-point scale from 0 - 10) with a recall period of 24 hours, and it was completed by the participant prior to drug administration at visits specified in the assessment schedule. A negative change from baseline implied improvement in pain. Change from baseline in function in patients global assessment (PGA) was analyzed using a MMRM including all time-points to compare treatment group. The model included baseline, treatment, timepoint and treatment-by-timepoints as fixed effects. Missing data is assumed to be Missing At Random (MAR). Based on second secondary estimand framework.	Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Actual): August 2, 2024
• Study Completion (Actual): April 8, 2025

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Osteoarthritis; Osteoarthritis of Knee; QUC398; Osteoarthritis of the Knee; Knee joint
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: CQUC398A12201; 2021-002795-39 (EudraCT Number); 2023-509274-28-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No