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

Osteoarthritis, Knee Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05462990
• Other study ID #: CQUC398A12201
• Secondary ID: 2021-002795-3920
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 9, 2022
• Est. completion date: October 6, 2025

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 101
• Est. completion date: October 6, 2025
• Est. primary completion date: November 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Christchurch
Australia	Novartis Investigative Site	Southport	Queensland
Australia	Novartis Investigative Site	St Leonards	New South Wales
Denmark	Novartis Investigative Site	Herlev
Denmark	Novartis Investigative Site	Vejle
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Orleans
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Leganes	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Sevilla
United States	Boston Univ School Of Medicine .	Boston	Massachusetts
United States	West Clinical Research Private Clinic	Morehead City	North Carolina
United States	Clinical Research of West FL Inc. .	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee	Week 12
Secondary	Cartilage volume of the knee index region	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in preservation of cartilage in the medial compartment of the target knee	Week 52
Secondary	Change from baseline in KOOS Pain subscale	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time	Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS)	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time	Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Change in Total KOOS	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	Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Change in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time	Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Secondary	Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS	Efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time	Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52