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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05462990

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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

Anticipated 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

Anticipated Study Start Date :

Oct 4, 2022

Anticipated Primary Completion Date :

Oct 2, 2023

Anticipated Study Completion Date :

Sep 2, 2024

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)

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

Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12 [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

Cartilage volume of the knee index region [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 [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) [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 [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 [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 [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

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Radiographic medial joint space width (mJSW) of 2 to 4 mm in men or 1.5 to 3.5 mm in women measured at the X=0.225 fixed point location within the medial tibio-femoral compartment of the target knee 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