A proof-of-concept study to examine QUC398 in participants with knee osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

3 Feb 2023 → 9 Apr 2025

Decision date (initial)

2024-04-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509274-28-00

EudraCT number

2021-002795-39

ClinicalTrials.gov

NCT05462990

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacogenetic, Efficacy, Safety, Others, Pharmacodynamic

To assess the efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee.

Secondary objectives 4

1. To assess the efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in preservation of cartilage in the medial compartment of the target knee.
2. To assess the efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving OA pain in the target knee over time.
3. To assess the efficacy of q4w s.c. injections of QUC398 300 mg vs placebo in relieving additional clinical symptoms and improving function in the target knee over time.
4. To assess the safety and tolerability of q4w s.c. injections of QUC398 300 mg vs placebo.

Conditions and MedDRA coding

Knee osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Weight ≥ 50 kg and a body mass index (BMI) between 18 -35 kg/m2, at Screening 1
2. 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
3. Radiographic medial joint space narrowing (mJSN) 1-2 within the medial tibio-femoral compartment of the target knee, confirmed by Xray at Screening 1
4. 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
5. Symptomatic OA with moderate to severe pain (corresponding to Pain NRS ≥ 5 to ≤ 9) in the target knee at Screening 1 and 2.
6. 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
7. KOOS pain subscale ≤ 60 in the target knee at Screening 1, Screening 2, and Screening 3

Exclusion criteria 6

1. 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.
2. Symptomatic, patello-femoral pain in the target knee as per investigator’s examination at Screening 1.
3. Severe malalignment > 7.5º in the target knee (either varus or valgus), measured using standardized knee X-ray at Screening 1.
4. Patient unable or unwilling to undergo MRI or presenting absolute contraindications to MRI.
5. Previous exposure to any ADAMTS-5 drug, including QUC398
6. History or current diagnosis of relevant cardiovascular diseases and ECG abnormalities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 9

1. Change from baseline in cartilage volume of the knee index region at Week 52, as determined from the automated segmentation of 3D-MRI scans
2. Change from baseline in KOOS Pain subscale at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
3. Change from baseline in pain assessed by a Pain Numerical Rating Scale (NRS) at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
4. Change from baseline in total KOOS at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
5. Change from baseline in KOOS subscales: Other symptoms, Function in daily living, Function in sport and recreation, and Knee related quality of life at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
6. Change from baseline in Patient's Global Assessment (PGA) as assessed by NRS at Weeks 1 (Day 5), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
7. Systemic and local Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, Electrocardiogram parameters (ECGs), Vital signs
8. Laboratory tests (Hematology, blood chemistry, coagulation and urinalysis)
9. Echo-Doppler of thoracic and abdominal aorta

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 20

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications