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

March 27, 2026 updated by: Novartis Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
101

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale at Week 12
Time Frame: Baseline, 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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Cartilage Volume of the Knee Index Region Measured by 3D-MRI
Time Frame: Baseline, Week 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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)
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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)
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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
Time Frame: Baseline, Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 9, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 2, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 8, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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