Phase IIb Randomized Double‑Blind Placebo‑Controlled Study of Intra‑Articular Allocetra‑OTS in Adults with Primary Knee Osteoarthritis

The primary objective is to evaluate the efficacy of intra‑articular Allocetra versus placebo in participants with Knee Osteoarthritis, using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score at 3 months as the primary efficacy endpoint; a demonstrated reduction in WOMAC scores would indicate clinically meaningful improvement in pain, stiffness, and functional limitation. Secondary objectives include: • assessment of additional efficacy parameters of Allocetra compared with placebo (e.g., secondary clinical scores, imaging findings, or biomarker changes); • evaluation of safety and tolerability of the intra‑articular administration, encompassing adverse event incidence, laboratory abnormalities, and local joint reactions.

The trial enrolled 195 participants diagnosed with Knee Osteoarthritis, encompassing both female and male subjects aged 64 years or older at screening. All individuals exhibited primary femorotibial knee OA confirmed by American College of Rheumatology clinical and radiographic criteria, with Kellgren‑Lawrence grades 2–3 on weight‑bearing X‑rays of the index knee. Participants reported persistent knee pain for at least three months, meeting specified WOMAC pain and function thresholds and maintaining a daily pain diary score of 4.5–9.0 on a 0–10 scale. The population consisted of patients who had failed at least two conventional OA therapies, including non‑pharmacological measures, analgesics, NSAIDs, steroid injections, or physical therapy, and were required to maintain stable use of permitted concomitant treatments while abstaining from prohibited medications. Women were required to be postmenopausal or surgically sterilized, and male participants with partners of childbearing potential needed to adhere to contraception requirements. All participants were capable of providing informed consent and complying with study procedures throughout the trial duration.

The study is a Phase IIb, multicenter investigation evaluating intra‑articular Allocetra‑OTS versus a matching placebo in adults with primary Knee Osteoarthritis. The design is randomized, double‑blind and placebo‑controlled, with participants allocated in a 1:1 ratio to receive a single intra‑articular injection of 200 million allogeneic peripheral blood mononuclear cells induced to an early apoptotic state or vehicle. The overall trial period for each participant extends from the screening visit through a final assessment at six months post‑dose, encompassing a primary efficacy evaluation at three months using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score. Study visits include: (1) a screening visit to confirm eligibility, perform radiographic confirmation, and collect baseline pain diaries and WOMAC assessments after a washout of analgesics; (2) a baseline/randomization visit on the same day as the injection; (3) follow‑up visits at approximately 1, 3, and 6 months to assess efficacy endpoints, safety labs, and adverse events; and (4) an end‑of‑study visit at six months for final outcome measurements. Participants are expected to remain in the study for roughly six months, with continued monitoring for safety up to six months. Early termination may occur if a participant experiences a serious adverse event related to the investigational product, violates key protocol requirements (e.g., prohibited concomitant treatments), withdraws consent, or if the investigator judges that continuation is not in the participant’s best interest.

The investigational product, Allocetra‑OTS, is provided as a sterile solution for injection. Each dose contains 200 million allogeneic peripheral blood mononuclear cells induced to an early apoptotic state. The preparation is administered by a single intra‑articular injection into the index knee joint.

The control arm receives a matching placebo vehicle. The placebo is supplied in the same pharmaceutical form and volume as the active product and is injected intra‑articularly using identical techniques.

All administrations are performed by trained study personnel under aseptic conditions. The injection site is observed for immediate reactions, and any adverse events are recorded. Documentation of each dose, including date, time, and volume, is entered into the case report form to confirm participant compliance with the dosing schedule.

Efficacy will be evaluated by quantifying the change from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score, normalized to a 0–100 scale, at the 3‑month visit. Additional efficacy parameters include the change from baseline in WOMAC sub‑scores for Pain+Function, Function, and Pain at both 3‑ and 6‑month assessments, as well as the WOMAC total score at 6 months. Patient‑reported pain will also be measured using the Average Daily Pain Numerical Rating Scale (ADP‑NRS), with changes from baseline assessed at 3 and 6 months.

All efficacy assessments will be conducted using validated questionnaires administered at baseline, 3 months, and 6 months post‑injection. Changes from baseline will be calculated for each endpoint and analyzed according to the predefined statistical analysis plan.