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

Phase 2TerminatedNCT05462990

Novartis Pharmaceuticals101 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

101

Conditions

Osteoarthritis, Knee

Interventions

QUC398DRUG

QUC398 150 mg/mL, solution for subcutaneous (s.c) injection (1 mL). 2 injections were administered to complete 300 mg.

PlaceboDRUG

Matching Placebo solution for s.c. injection (1 mL). 2 injections were administered per dose to ensure blinding.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (14)

Clinical Research of West Florida Inc

Tampa, Florida, United States

Boston Univ School of Medicine

Boston, Massachusetts, United States

West Clinical Research

Morehead City, North Carolina, United States

Outcomes

Primary Outcomes

Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale at 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.

Time frame: Baseline, Week 12

Secondary Outcomes

Change From Baseline in Cartilage Volume of the Knee Index Region Measured by 3D-MRI

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.

Time frame: Baseline, Week 52

Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale

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.

Data from ClinicalTrials.gov

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Novartis Investigative Site

Southport, Queensland, Australia

Novartis Investigative Site

Christchurch, Australia

Novartis Investigative Site

St Leonards, Australia

Novartis Investigative Site

Herlev, Denmark

Novartis Investigative Site

Vejle, Denmark

Novartis Investigative Site

Nice, France

Novartis Investigative Site

Orléans, France

...and 4 more locations

Time frame: 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)

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.