Clinical trial NCT05462990: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: QUC398
Osteoarthritis of Knee
Osteoarthritis of the Knee
Knee joint
Osteoarthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 101
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain sub-scale at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Cartilage volume of the knee index region
timeFrame: Week 52
measure: Change from baseline in KOOS Pain subscale
timeFrame: Weeks 1 (Day 5), 4, 8, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS)
timeFrame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change in Total KOOS
timeFrame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life
timeFrame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS
timeFrame: Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Clinical Research of West Florida Inc
state: Florida
city: Boston
country: United States
facility: Boston Univ School Of Medicine
state: Massachusetts
city: Morehead City
country: United States
facility: West Clinical Research
state: North Carolina
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Christchurch
country: Australia
facility: Novartis Investigative Site
city: St Leonards
country: Australia
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Orleans
country: France
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Leganes
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Sevilla
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: