A randomized, placebo controlled, investigator and participant-blinded study, investigating safety, tolerability and efficacy of RHH646 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

1 Sep 2023 → 24 Feb 2025

Decision date (initial)

2023-06-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG, OMS ID: ORG-100003908

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Others, Pharmacokinetic, Efficacy

1. To evaluate the articular cartilage-regenerating capacity of RHH646 in the knee following 1 year of treatment
2. To evaluate the safety and tolerability of RHH646 following 1 year of treatment

Secondary objectives 1

1. To evaluate the pharmacokinetics of RHH646 in patients with knee OA

Conditions and MedDRA coding

Knee Osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant is >/= 35 and </=75 years old at time of screening
2. Participant must weigh at least 50 kg and have a body mass index (BMI) </= 35 kg/m2
3. Diagnosis of tibiofemoral OA in at least one knee by standard American College of Rheumatology (ACR) clinical and radiographic criteria at screening
4. K&L grade 2 to 3 OA in the target knee evaluated by X-Ray by the Central reader at screening
5. Predominantly medial tibiofemoral compartment involvement defined as medial Joint Space Narrowing (medJSN) 1-2 and medJSN > lateral Joint Space Narrowing (latJSN) in the target knee evaluated by X-Ray by the Central Reader at screening
6. Symptomatic disease, defined as having pain in the knee at least 3 days per week during the last 3 months from screening that is relieved by analgesic therapy (e.g., APAP or NSAIDs), according to the investigator’s evaluation and judgement of patient’s history

Exclusion criteria 10

1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
2. Arthroscopy of the target knee within the 6 months prior to screening or planned arthroscopy during the study
3. Previous surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy >50% or osteotomy; planned surgery for either knee during the study
4. Unstable target knee joint or insufficiently reconstructed ligaments based on medical history and/or physical examination by the investigator
5. Participant has severe malalignment (valgus or varus deformity) in the target knee >7.5° based on X-Ray evaluation by the Central Reader at screening
6. K&L grade 4 OA in either knee
7. Presence of severe hip OA that either (i) alters lower limb function to a degree that increases or abnormally changes the mechanical forces in the knee while walking according to the investigator’s evaluation or (ii) currently requires or is likely to require specific medical or surgical management during the study period
8. Other pathologies affecting the knee, including subchondral insufficiency fractures, bone fracture (acute or subacute within the 6 months prior to screening) or bone bruise, osteonecrosis, malignant bone marrow infiltration, solid tumors and/or patellofemoral dysplasia bbased on clinical assessment or imaging
9. Known autoimmune disease with inflammatory arthritis, crystal-induced arthritides (gout or pseudogout arthritis), active acute or chronic infection of the knee joint, Lyme disease involving the knee, reactive arthritis, systemic cartilage disorders, moderate to severe fibromyalgia, a known systemic connective tissue disease or a widespread pain index >4
10. Inability to undergo MRI (e.g. claustrophobia, body size, leg not fitting in the coil) or contraindications to MRI (e.g. non-MRI compatible metallic implants, metallic foreign bodies, pacemaker, defibrillator)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from baseline in cartilage volume in the index region of the target knee by MRI at Week 52
2. Adverse Events (AEs) Electrocardiograms (ECGs) Vital signs Hematology, blood chemistry, urinalysis

Secondary endpoints 1

1. RHH646 plasma concentrations, Cmin,ss at Week4 and any other PK parameter as appropriate

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

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 17

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

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

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 30 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