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

• ClinicalTrials.gov Identifier: NCT05462990
• Recruitment Status: Recruiting
• First Posted: July 18, 2022
• Last Update Posted: April 5, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of the study is to find out if the investigational treatment named QUC398 has beneficial effects on osteoarthritis knee pain and knee cartilage, and if it is safe and well tolerated.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: QUC398; Drug: Placebo	Phase 2

Detailed Description:

This is a phase IIa study to establish the effect of QUC398 on pain and cartilage preservation in participants with symptomatic knee OA

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: participant, investigator and sponsor-blinded
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 9, 2022
• Estimated Primary Completion Date: November 4, 2024
• Estimated Study Completion Date: October 6, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: QUC398; QUC398 150 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to complete the 300 mg	Drug: QUC398; QUC398 150 mg/mL, solution for s.c. injection (1 mL)
Placebo Comparator: Placebo; Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding	Drug: Placebo; Placebo 0 mg/mL, solution for s.c. injection (1 mL)

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12 [ Time Frame: Week 12 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee

Secondary Outcome Measures :

1. Cartilage volume of the knee index region [ Time Frame: Week 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in preservation of cartilage in the medial compartment of the target knee
2. Change from baseline in KOOS Pain subscale [ Time Frame: Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
3. Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS) [ Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
4. Change in Total KOOS [ Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving clinical symptoms and improving function in the target knee over time
5. Change in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life [ Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time
6. Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS [ Time Frame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
   Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Locations

United States, Florida

CoastalOrthoandSportsMedofSWFlorida .; Recruiting

Bradenton, Florida, United States, 34209

Contact: Caitlin Towsley 941-792-1404 ctowsley@coastalorthopedics.com

Principal Investigator: David Cashen

Meridien Research; Recruiting

Maitland, Florida, United States, 32751

Contact: Lindsay Theisen 407-644-1165 lindsay.theisen@accelclinical.com

Principal Investigator: Eva Maria Heurich

Clinical Research of West FL Inc. .; Recruiting

Tampa, Florida, United States, 33603

Contact: Rachel Matthews 813-870-1292 rmatthews@crwf.com

Principal Investigator: Paul A Lunseth

United States, Massachusetts

Boston Univ School Of Medicine .; Recruiting

Boston, Massachusetts, United States, 02118

Contact: Rutvi Patel rutvip@bu.edu

Principal Investigator: Tuhina Neogi

United States, North Carolina

West Clinical Research Private Clinic; Recruiting

Morehead City, North Carolina, United States, 28557

Contact: Millicent Clark millicent.clark@westclinicalresearch.com

Principal Investigator: Jeffrey K Moore

Australia, New South Wales

Novartis Investigative Site; Recruiting

St Leonards, New South Wales, Australia, 2065

Australia, Queensland

Novartis Investigative Site; Recruiting

Southport, Queensland, Australia, 4222

Australia, Tasmania

Novartis Investigative Site; Withdrawn

Hobart, Tasmania, Australia, 7000

Australia

Novartis Investigative Site; Recruiting

Christchurch, Australia, 8011

Denmark

Novartis Investigative Site; Recruiting

Herlev, Denmark, 2730

Novartis Investigative Site; Recruiting

Vejle, Denmark, 7100

France

Novartis Investigative Site; Recruiting

Nice, Cedex1, France, 06001

Novartis Investigative Site; Withdrawn

Lille, Hauts De France, France, 59160

Novartis Investigative Site; Withdrawn

Lyon, France, 69437

Novartis Investigative Site; Recruiting

Orleans, France, 45100

Novartis Investigative Site; Recruiting

Paris, France, 75012

Norway

Novartis Investigative Site; Withdrawn

Oslo, Norway, 370

Novartis Investigative Site; Withdrawn

Oslo, Norway, NO 0450

Spain

Novartis Investigative Site; Recruiting

Sabadell, Barcelona, Spain, 08208

Novartis Investigative Site; Recruiting

Barcelona, Cataluna, Spain, 08022

Novartis Investigative Site; Recruiting

La Coruna, Galicia, Spain, 15006

Novartis Investigative Site; Recruiting

Leganes, Madrid, Spain, 28915

Novartis Investigative Site; Recruiting

Sevilla, Spain, 41010

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05462990
• Other Study ID Numbers: CQUC398A12201; 2021-002795-39 ( EudraCT Number ); 2023-509274-28-00 ( Other Identifier: EU CT )
• First Posted: July 18, 2022
• Last Update Posted: April 5, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases