Randomized, Double-Blind, Placebo-Controlled Study of Intra-Articular Allocetra-OTS in Patients with Knee Osteoarthritis
- Trial ID
- 2023-508748-23-00
- Protocol
- ENX-CL-05-001
- Sponsor
- Enlivex Therapeutics Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 1/2a randomized, double-blind, placebo-controlled study is to evaluate the **safety** and tolerability of Allocetra when administered via intra-articular injection to the index knee joint in patients with knee osteoarthritis. This objective is clinically relevant as it aims to determine the appropriate dose and regimen of Allocetra, a potential therapeutic agent, ensuring its safe application in the treatment of knee osteoarthritis. The study is divided into two phases: a safety run-in phase to characterize safety and select the dose, and a randomized phase to compare safety and tolerability against a placebo.
Secondary objectives include assessing the **efficacy** of intra-articular Allocetra administration to the index knee joint compared to placebo as a treatment for knee osteoarthritis. This evaluation is crucial for understanding the potential therapeutic benefits of Allocetra in alleviating symptoms associated with knee osteoarthritis.
Participants
The clinical trial involves a total of **54 participants** diagnosed with **knee osteoarthritis**. The study population includes both male and female subjects, aged between **45 and 80 years**. Participants were selected based on specific criteria, including chronic osteoarthritis of the index knee with a pain score of at least 4 out of 10 when not using medication, and radiographic evidence of knee osteoarthritis of Kellgren-Lawrence Grade 2 or 3. The trial population is characterized by individuals who have not adequately responded to at least three months of conventional therapy. Participants are required to abstain from other intra-articular treatments and adhere to protocol restrictions regarding concomitant medications and therapies during the study. The study includes individuals who are willing to use adequate contraception methods and comply with study procedures, including follow-up visits. The trial does not exclude vulnerable populations, and participants must provide informed consent and demonstrate the ability to comply with all study requirements.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the safety and tolerability of **Allocetra-OTS**, a **solution for injection** containing **allogeneic peripheral blood mononuclear cells induced to an early apoptotic state**, administered via **intra-articular injection** in patients with **knee osteoarthritis**. The trial is structured in two phases: a safety run-in phase to determine the appropriate dose and regimen, followed by a randomized phase to compare the safety and tolerability of Allocetra-OTS against a matching placebo. The study is expected to commence recruitment on March 1, 2024, and conclude by February 27, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, chronicity of osteoarthritis, and radiographic evidence of knee osteoarthritis. Eligible participants will be required to report knee pain levels and adhere to specific medication restrictions. The trial will include follow-up visits at 3, 6, and 12 months post-treatment to evaluate primary and secondary endpoints, including adverse events, changes in knee pain, and quality of life assessments. The end-of-study visit will mark the completion of the participant's involvement, which is anticipated to last up to 12 months from the last study treatment administration.
Participants may be withdrawn from the study if they experience severe adverse events, fail to comply with study procedures, or choose to discontinue participation. The primary endpoint focuses on the number and severity of adverse events, while secondary endpoints include changes in knee pain, WOMAC scores, and quality of life measures. The trial aims to provide comprehensive data on the safety and efficacy of Allocetra-OTS in managing knee osteoarthritis, contributing to the development of novel therapeutic options for this condition.
Treatment
The clinical trial involves the administration of **Allocetra-OTS**, an experimental medication formulated as a **solution for injection**. The active substance in Allocetra-OTS is **allogeneic peripheral blood mononuclear cells induced to an early apoptotic state**, which is a structurally diverse substance used in cell therapy. The medication is administered via **intra-articular injection** directly into the index knee joint. The trial includes a safety run-in phase to determine the appropriate dose and regimen, followed by a randomized phase to assess safety and tolerability. The dosing schedule and frequency of administration are determined based on the safety and tolerability outcomes from the initial phase. Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.
The study also includes a **matching placebo (vehicle)**, which serves as the comparator treatment. The placebo is designed to mimic the experimental medication in appearance and administration route but does not contain the active therapeutic substance. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of the treatment's efficacy and safety. The placebo is administered via the same intra-articular route as Allocetra-OTS, maintaining consistency in the administration process across all study participants.
Efficacy
Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the safety profile, specifically the number and severity of adverse events (AEs), serious adverse events (SAEs), and any treatment disruptions or discontinuations. These will be monitored throughout the study, from Day 0 up to 6 months following the last injection.
Secondary endpoints will evaluate the efficacy of Allocetra in improving symptoms of knee osteoarthritis. These include the change from baseline in the weekly average of knee pain, measured using a Numeric Rating Scale (NRS), at 3 and 6 months post-treatment. Additionally, changes from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, as well as pain, stiffness, and disability sub-scores, will be assessed at 3, 6, and 12 months following the last treatment. Quality of life improvements will be measured using the Euro Quality of Life-5-dimension (EQ-5D) questionnaire at 6 and 12 months. The use of analgesics will also be tracked at 3, 6, and 12 months post-treatment.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 45 – 80 years
- 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.
- Radiographic evidence of knee osteoarthritis of Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee, assessed by X-ray.
- 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.
- Patients with knee pain who have failed to respond adequately to at least 3 months of conventional therapy.
- Willing to abstain from other intra-articular treatments and adhere to the protocol restrictions for concomitant medications and therapies during the study.
- 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.
- 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.
- 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
- Wheelchair bound.
- Any live vaccine administered less than 30 days prior to the screening visit.
- 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).
- Any known current or prior tumor of the index knee.
- Any known history or current intra-articular or osseous infection of the index knee.
- Pain in the contralateral knee of NRS 5 or more.
- Any evidence of clinically significant active infection anywhere in the body within a week prior to screening visit.
- 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.
- Any known severe systemic cartilage and/or bone disorder, such as, but not limited to, chondrodysplasia, or osteogenesis imperfecta.
- BMI >40.
- 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).
- 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.
- Any ligamentous repair or malalignment correction in the index knee within 6 months prior to screening visit.
- Major injury to the index knee, such as torn ligament or severe sprain within 6 months prior to screening visit.
- 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.
- Large size synovial fluid effusion of the index knee at the screening visit.
- Valgus or varus alignment of the index knee >10 degrees or knee flexion contracture > 10 degrees.
- Dermatologic lesions on index knee that may interfere with injection site.
- Severe hip osteoarthritis ipsilateral to the index knee.
- Clinically significant widespread pain syndromes, as assessed by the Investigator, e.g., fibromyalgia, long COVID syndrome.
- Known hypersensitivity to any component of the study treatment or its excipients.
- Receipt of an IP or participation in other interventional clinical trials within 60 days prior to screening visit, unless approved by the Sponsor.
- Known coagulopathy, or use of anticoagulation medication or antiaggregant medication; however, up to 150 mg ASA daily is allowed.
- Previous intra-articular injection of steroid, hyaluronate, or other agent, into the index knee within 3 months prior to screening visit.
- 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.
- 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.
- Known HIV infection (acute or chronic), uncured hepatitis C or hepatitis B infection.
- 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).
- Female patient is pregnant or breastfeeding, or planning to become pregnant or initiate breastfeeding while enrolled in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Recruiting | 01 Mar 2024 | 156 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Matching placebovehicle | Placebo | N/A | — | — | — | N/A |
Allocetra-OTS | Test | SUSPENSION FOR INFUSION | INTRA-ARTICULAR INJECTION | — | — | PRD9791454 |