Study of efficacy, safety, and tolerability of LNA043 in patients with symptomatic 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

21 Jul 2021 → 29 May 2025

Decision date (initial)

2024-05-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-509937-37-00

EudraCT number

2020-004897-22

ClinicalTrials.gov

NCT04864392

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacokinetic, Safety, Efficacy, Pharmacodynamic

To evaluate knee structural changes from baseline in the central medial tibiofemoral compartment (cMTFC) of LNA043 compared with placebo in the target knee at Week 104.

Secondary objectives 6

1. To evaluate changes from baseline in OA pain in the target knee of LNA043 compared with placebo at Week 104
2. To evaluate changes from baseline in physical function of LNA043 compared with placebo at Week 104
3. To evaluate structural changes from baseline in the total, medial and lateral tibiofemoral compartment (TFCs) in the target knee of LNA043 compared with placebo at Week 104
4. To evaluate changes from baseline in performance- based physical function assessment of LNA043 compared with placebo at Week 104
5. To evaluate structural progression in the target knee of LNA043 compared with placebo using imaging techniques
6. To evaluate safety and tolerability of the various LNA043 regimens

Conditions and MedDRA coding

Osteoarthritis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males and females between 40 and 75 years of age
2. Body mass index (BMI) < 40 kg/m2
3. Diagnosis of primary tibiofemoral knee OA by standard American College of Rheumatology clinical and radiographic criteria
4. Radiographic disease K-L grade 2 or 3 knee OA with predominantly medical TFC involvement defined as medial Joint Space Narrowing (medJSN) 1-2 and medJSN> lateral Joint Space Narrowing (latJSN) in the target knee
5. Participants with WOMAC pain of 20-45 (out of 50) for the target knee at both (double baseline) assessments during screening period after discontinuation of analgesics, anti-inflammatories and low potency opioids within 48 hours an equivalent of 5xT ½ wash out period (whichever is longer)
6. Symptomatic OA with pain in the target knee for at least 6 months
7. Primary source of pain throughout body is due to OA in the target knee: Widespread Pain Index score of ≤6 and a Symptom Severity score of < 7

Exclusion criteria 10

1. Participants with radiographic knee OA K-L grade = 4 on the non-target knee
2. Participants with WOMAC Pain >15 (out of 50)v in the non-target knee
3. Severe malalignment (>7.5 ° varus or valgus) in the anatomical axis of the target knee
4. Clinical signs of moderate- severe inflammation (i.e., redness, warmth, effusion) of the target knee or requiring aspiration in the target knee within 12 weeks prior Screening
5. Arthroscopy of the target knee within the 6 months prior to Screening
6. Previous surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% or osteotomy, partial or complete joint replacement or planned knee surgery for either knee during the study
7. Unstable target knee joint (including, but not limited to, posttraumatic or congenital laxity) or insufficiently reconstructed ligaments based on medical history and/or physical examination by the Investigator
8. Other pathologies affecting the knee, including subchondral insufficiency fractures, bone fracture (acute or subacute in less than 6 months prior to screening) or bone bruise, osteonecrosis, malignant bone marrow infiltration, solid tumors, and/or patellofemoral dysplasia based on clinical assessment, X-ray or MRI
9. Symptomatic hip OA on either hip or hip prosthesis recently implanted (within 1 year) or foreseen within the study period (either hip)
10. Other pain conditions that could confound assessments of the pain associated with knee OA, as judged by the Investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the knee structure

Secondary endpoints 6

1. Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain
2. Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function
3. Change from baseline in cartilage structure
4. Change from baseline in physical function
5. Proportion of participants demonstrating structural progression
6. Assessing adverse events and serious adverse events

Investigational products

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

Test 1

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 21

Locations

5 EU/EEA countries · 23 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 5 · 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 75 files

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

Application history

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