A Phase 1/2a Randomized, Double-Blind Placebo-controlled Study of Intra-articular Allocetra in Knee Osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Enlivex Therapeutics Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

26 Mar 2024 → 3 Mar 2026

Decision date (initial)

2024-03-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Safety run-in phase: To characterize the safety and tolerability and select the dose and regimen of Allocetra for the randomized phase, when administered via intra-articular injection to the index knee joint in different doses.
Randomized phase: To assess the safety and tolerability of Allocetra when administered via intra-articular injection to the index knee joint in comparison to placebo

Secondary objectives 1

1. To assess the efficacy of intra-articular Allocetra administration to the index knee joint in comparison to placebo as treatment for knee osteoarthritis.

Conditions and MedDRA coding

Knee osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age 45 – 80 years
2. Chronic osteoarthritis of index knee with knee-related joint pain: At the screening visit, patient reports that their typical osteoarthritis knee pain when not using medication is ≥ 4 out of 10.
3. Radiographic evidence of knee osteoarthritis of Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee, assessed by X-ray.
4. At least 4 measurements of daily pain in the index knee on a NRS of at least 5 out of 10, and no single score of more than 9, assessed over a period of 7 days during the screening period and following washout of at least 48 hours. If the patient is receiving a long-acting analgesic the washout will be extended to 5- half-lives of the analgesic medication(s). Acetaminophen and/or metamizole (dipyrone) may be used for pain during the weekly assessment.
5. Patients with knee pain who have failed to respond adequately to at least 3 months of conventional therapy.
6. Willing to abstain from other intra-articular treatments and adhere to the protocol restrictions for concomitant medications and therapies during the study.
7. Women of childbearing potential and all men must agree to use 2 methods of an adequate contraception: One barrier method (e.g., diaphragm, or condom or sponge, each of which are to be combined with a spermicide) and one hormonal method (e.g., oral, transdermal patch, implanted contraceptives or intrauterine device) prior to study entry and for the duration of study participation through 4 weeks following IP administration. Subjects that are highly unlikely to conceive (e.g., surgically sterile, postmenopausal, or not heterosexually active) are exempt.
8. Ability of the patient to understand, and willingness to provide informed consent as described in this study protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
9. At the discretion of the Investigator, ability to comply with all study procedures, availability for the duration of the study, and ability and willingness to return for follow-up visits.

Exclusion criteria 29

1. Wheelchair bound.
2. Any live vaccine administered less than 30 days prior to the screening visit.
3. Immunosuppressive therapy, including oral (but not inhaled or topical) corticosteroids, less than 90 days prior to the screening visit. Oral corticosteroid treatment for diseases other than the disease under study, up to 5 mg per day is allowed (e.g., asthma).
4. Any known current or prior tumor of the index knee.
5. Any known history or current intra-articular or osseous infection of the index knee.
6. Pain in the contralateral knee of NRS 5 or more.
7. Any evidence of clinically significant active infection anywhere in the body within a week prior to screening visit.
8. Any known history of inflammatory arthropathy or crystal-deposition arthropathy including rheumatoid arthritis, psoriatic arthritis, gout, pseudogout, chondrocalcinosis, hemochromatosis, villonodular synovitis, and synovial chondromatosis, or other disorder other than osteoarthritis that in the opinion of the Investigator could cause inflammation of the knee.
9. Any known severe systemic cartilage and/or bone disorder, such as, but not limited to, chondrodysplasia, or osteogenesis imperfecta.
10. BMI >40.
11. Any malignancy requiring active treatment within the last 3 years prior to screening (with the exception of non-melanoma skin cancer and in-situ breast cancer).
12. Any major surgical cartilage treatment (such as, but not limited to, ACI, OATS) in the index knee within 12 months prior to screening, or any minor surgical cartilage treatment (such as, but not limited to, microfracture) within 6 months prior to screening.
13. Any ligamentous repair or malalignment correction in the index knee within 6 months prior to screening visit.
14. Major injury to the index knee, such as torn ligament or severe sprain within 6 months prior to screening visit.
15. Clinically relevant knee instability of the index knee on physical examination. Patients with clinically well-compensated instability such as well compensated ACL instability can be included.
16. Large size synovial fluid effusion of the index knee at the screening visit.
17. Valgus or varus alignment of the index knee >10 degrees or knee flexion contracture > 10 degrees.
18. Dermatologic lesions on index knee that may interfere with injection site.
19. Severe hip osteoarthritis ipsilateral to the index knee.
20. Clinically significant widespread pain syndromes, as assessed by the Investigator, e.g., fibromyalgia, long COVID syndrome.
21. Known hypersensitivity to any component of the study treatment or its excipients.
22. Receipt of an IP or participation in other interventional clinical trials within 60 days prior to screening visit, unless approved by the Sponsor.
23. Known coagulopathy, or use of anticoagulation medication or antiaggregant medication; however, up to 150 mg ASA daily is allowed.
24. Previous intra-articular injection of steroid, hyaluronate, or other agent, into the index knee within 3 months prior to screening visit.
25. Any of the following laboratory values at screening: hemoglobin <8.5 gm/dL, WBC <3500 per mm3 or >15,000 per mm3, platelet count <100,000/uL, creatinine >2 mg/dL, bilirubin >2 mg/dL, aspartate aminotransferase or alanine aminotransferase >3-fold higher than the ULN or international normalized ratio >1.2.
26. Known severe cardiac or respiratory diseases including uncompensated congestive heart failure, ventricular arrhythmias, acute coronary disease, myocardial infarction within 6 months prior to screening visit, unstable angina, uncontrolled hypertension, severe pulmonary disease, or uncontrolled asthma.
27. Known HIV infection (acute or chronic), uncured hepatitis C or hepatitis B infection.
28. Any known psychiatric condition that, in the opinion of the Investigator, would make the patient unsuitable for the study (e.g., severe depression, suicidal ideation, or known drug or alcohol abuse within 1 year prior to screening visit).
29. Female patient is pregnant or breastfeeding, or planning to become pregnant or initiate breastfeeding while enrolled in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number and severity of adverse events (AEs), serious adverse events (SAEs) and treatment disruptions/ discontinuations throughout the study from Day 0 and up to 6 months following the last injection

Secondary endpoints 6

1. Evaluation of change from baseline in weekly average of knee pain as measured using a NRS, assessed at 3 months and 6 months from last study treatment.
2. Change from baseline in WOMAC total score at 3 months, 6 months, and 12 months from last study treatment administration.
3. Change from baseline in WOMAC pain sub-scores at 3 months, 6 months, and 12 months from last study treatment administration.
4. Change from baseline in WOMAC stiffness and disability sub-scores at 3 months, 6 months, and 12 months from last study treatment administration.
5. Change from baseline in QoL as measured by Euro Quality of Life-5-dimension (EQ-5D) questionnaire at 6 months and at 12 months from last study treatment administration.
6. Use of analgesics by 3 months, 6 months, and 12 months from last study treatment administration.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Enlivex Therapeutics Ltd.

Sponsor organisation

Enlivex Therapeutics Ltd.

Address

P. O. Box 12167

City

Jerusalem

Postcode

9574425

Country

Israel

Scientific contact point

Organisation

Enlivex Therapeutics Ltd.

Contact name

VP Clinical

Public contact point

Organisation

Enlivex Therapeutics Ltd.

Contact name

CEO

Locations

1 EU/EEA country · 3 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

Documents 16 files

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

Application history

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