Clinical trial NCT06233474: Study of Intra-articular Allocetra in Knee Osteoarthritis
Official title: A Phase 1/2a Randomized, Double-Blind Placebo-controlled Study of Intra-articular Allocetra in Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis, Knee
Lead sponsor: Enlivex Therapeutics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Nordic Bioscience Clinical Development (NBCD)
First posted: 2024-01-31
Enrollment: 160
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Run-in phase followed by randomization phase
Primary purpose: TREATMENT

Brief summary: This is a double blind, randomized,multi-center study to evaluate the safety and efficacy of intra-articular administration of Allocetra compared to placebo in patients with symptomatic knee osteoarthritis.

Detailed description: Knee osteoarthritis is a degenerative disease driven by physical breakdown of the joint cartilage, together with a chronic inflammation within the knee space. Over time, many patients will develop worsening pain in the joint and functional impairment, which may ultimately require knee replacement.

Allocetra is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state.

This Phase 1/2a study is comprised of an open-label safety run-in stage to characterize safety and tolerability of repeated injections of Allocetra to a target knee , followed by a double-blind randomized stage to evaluate the safety and efficacy of Allocetra repeated injections to the target knee compared to placebo, in moderate to severe knee osteoarthritis patients. Patients in both stages will be followed for up to a year following last treatment. the last treatment.

Eligibility criteria: Inclusion Criteria:

1. Age 45 - 80 years.
2. Chronic osteoarthritis of index knee with knee-related joint pain
3. Radiographic evidence of knee osteoarthritis of K-L Grade 2 or 3 in the index knee.
4. Knee pain assessed daily over a period of 7 days during the screening period and following wash-out of pain medications
5. Patients with chronic knee pain for at least 3 months who have failed to respond adequately to 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 prior to study entry and for the duration of study participation through 4 weeks following IP administration.

Exclusion Criteria:

1. Wheelchair bound.
2. Immunosuppressive therapy
3. Any known current or prior tumor of the index knee.
4. Any known history or current intra-articular or osseous infection of the index knee.
5. Any evidence of clinically significant active infection
6. Any known history of inflammatory arthropathy or crystal-deposition arthropathy
7. Any known severe systemic cartilage and/or bone disorder, such as, but not limited to, chondrodysplasia, osteogenesis imperfecta.
8. Body Mass Index (BMI) \>40.
9. Any major surgical cartilage treatment within 6 months
10. Any ligamentous repair or malalignment correction in the index knee within 6 months
11. Major injury to the index knee, such as torn ligament or severe sprain within 6 months
12. Clinically relevant knee instability of the index knee
13. Severe hip osteoarthritis ipsilateral to the index knee.
14. Clinically significant widespread pain syndromes, e.g., fibromyalgia, long COVID syndrome.
15. Known coagulopathy, or use of anticoagulation medication or antiaggregant medication;.
16. certain tumors, severe cardiac, respiratory or hematologic diseases as defined in the protocol

Primary outcomes:
measure: Treatment-emergent adverse events and Serious adverse events following Allocetra-OTS injection
timeFrame: 7 months following Day 0
Secondary outcomes:
measure: Weekly average of knee pain.
timeFrame: 4 months and 7 months following Day 0.
measure: Change from baseline in WOMAC total score.
timeFrame: 4 months, 7 months and 13 months following Day 0.
measure: Change in quality of life- Euro Quality of Life-5-dimension (EQ-5D) questionnaire
timeFrame: 4 months, 7 months and 13 months following Day 0.
Other outcomes:
Locations:
city: Gandrup
country: Denmark
facility: Sanos Clinic Nordjylland
city: Herlev
country: Denmark
facility: Sanos Clinic Herlev
city: Vejle
country: Denmark
facility: Sanos Clinic Syddanmark
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petach Tikva
country: Israel
facility: Hasharon Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Ichilov - Tel Aviv Sourasky Medical Center
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul de Cardiologie
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clininc Republican "T. Mosneaga"
city: Chisinau
country: Moldova, Republic of
facility: IMSP Sptalul Clinic Municipal "Sfanta Treime"
Study officials:
affiliation: Senior Director of Clinical Operations
name: Lital Weinfeld-Bergman
role: STUDY_DIRECTOR
References: