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

NCT05462990 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: CQUC398A122012021-002795-392023-509274-28-00
• Study Type: interventional
• Target: 101
• Locations: 5 countries
• Sites: 14

Brief Summary

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.

Conditions

Osteoarthritis, Knee

Keywords

QUC398; Osteoarthritis of Knee; Osteoarthritis of the Knee; Knee joint; Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Change From Baseline in Cartilage Volume of the Knee Index Region Measured by 3D-MRI

  Baseline, Week 52

• Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale

  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)

  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)

  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

  Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Study Arms (2)

QUC398 300 mg

EXPERIMENTAL

QUC398 was administered subcutaneous every 4 weeks during 48 weeks.

Drug: QUC398

Placebo

PLACEBO COMPARATOR

Placebo was administered subcutaneous every 4 weeks during 48 weeks.

Drug: Placebo

Interventions

QUC398 DRUG

QUC398 150 mg/mL, solution for subcutaneous (s.c) injection (1 mL). 2 injections were administered to complete 300 mg.

QUC398 300 mg

Placebo DRUG

Matching Placebo solution for s.c. injection (1 mL). 2 injections were administered per dose to ensure blinding.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Clinical Research of West Florida Inc

Tampa, Florida, 33603, United States

Location

Boston Univ School of Medicine

Boston, Massachusetts, 02118, United States

Location

West Clinical Research

Morehead City, North Carolina, 28557, United States

Location

Novartis Investigative Site

Southport, Queensland, 4222, Australia

Location

Novartis Investigative Site

Christchurch, 8011, Australia

Location

Novartis Investigative Site

St Leonards, 2065, Australia

Location

Novartis Investigative Site

Herlev, 2730, Denmark

Location

Novartis Investigative Site

Vejle, 7100, Denmark

Location

Novartis Investigative Site

Nice, 06001, France

Location

Novartis Investigative Site

Orléans, 45100, France

Location

Novartis Investigative Site

Sabadell, Barcelona, 08208, Spain

Location

Novartis Investigative Site

Leganés, Madrid, 28915, Spain

Location

Novartis Investigative Site

A Coruña, 15006, Spain

Location

Novartis Investigative Site

Seville, 41010, Spain

Location

Related Links

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

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Limitations and Caveats

The decision to terminate the study early, resulted in fewer participants contributing data at the later timepoints.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: participant, investigator and sponsor-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 18, 2022
• Study Start: November 9, 2022
• Primary Completion: August 2, 2024
• Study Completion: April 8, 2025
• Last Updated: March 31, 2026
• Results First Posted: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); DK (2); ES (4); US (3); FR (2)