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 29, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: July 14, 2022
• First Posted Date: July 18, 2022
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: November 9, 2022
• Estimated Primary Completion Date: November 4, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 4, 2024)

• 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
• 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
• 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
• 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
• 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
• 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

Original Secondary Outcome Measures (submitted: July 14, 2022)

• 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
• Change from baseline in KOOS Pain subscale [ 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
• 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
• 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
• 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
• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Proof-of-concept Study to Examine QUC398 in Participants With Knee OA
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

participant, investigator and sponsor-blinded

Primary Purpose: Treatment

• Condition: Osteoarthritis, Knee

Intervention

• Drug: QUC398
  QUC398 150 mg/mL, solution for s.c. injection (1 mL)
• Drug: Placebo
  Placebo 0 mg/mL, solution for s.c. injection (1 mL)

Study Arms

• 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
  Intervention: Drug: QUC398
• Placebo Comparator: Placebo
  Placebo 0 mg/mL, solution for s.c. injection (1 mL). 2 injections will be applied per dose to ensure blinding
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 14, 2022): 98
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 6, 2025
• Estimated Primary Completion Date: November 4, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: United States, Australia, Denmark, France, Norway, Spain

Administrative Information

• NCT Number: NCT05462990
• Other Study ID Numbers: CQUC398A12201; 2021-002795-39 ( EudraCT Number ); 2023-509274-28-00 ( Other Identifier: EU CT )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: April 2024