Study of Intra-articular Allocetra in Knee Osteoarthritis

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06233474
• Other study ID #: ENX-CL-05-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 26, 2024
• Est. completion date: February 1, 2026

Study information

• Verified date: May 2024
• Source: Enlivex Therapeutics Ltd.
• Contact: Lior Binder
• Phone: +972-54-8054599
• Email: lior[@]enlivexpharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: February 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

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 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 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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Allocetra
Allocetra-OTS is a cell-based therapy consisting of non-HLA-matched allogeneic peripheral blood mononuclear cells, induced to an apoptotic stable state

Other:
• Placebo
The control used in this study will be placebo. Placebo solution containing all excipients except for the Allocetra cells.

Locations

Country	Name	City	State
Denmark	Sanos Clinic Nordjylland	Gandrup
Denmark	Sanos Clinic Herlev	Herlev
Denmark	Sanos Clinic Syddanmark	Vejle
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Medical Center	Haifa
Israel	Beilinson Medical Center	Petach Tikva
Israel	Hasharon Medical Center	Petach Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Re?ovot
Israel	Ichilov - Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (2)

Lead Sponsor	Collaborator
Enlivex Therapeutics Ltd.	Nordic Bioscience Clinical Development (NBCD)

Countries where clinical trial is conducted

Denmark,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent adverse events and Serious adverse events following Allocetra-OTS injection	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	7 months following Day 0
Secondary	Weekly average of knee pain.	Evaluation of change from baseline in weekly average of knee pain as measured using NRS (Numeric Rating Scale ) assessed at 3 months and 6 months from last study treatment.; Scores range from 0-10 points, with higher scores indicating greater pain intensity	4 months and 7 months following Day 0.
Secondary	Change from baseline in WOMAC total score.	Change from baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score at 3 months, 6 months, and 12 months from last study treatment administration.; Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.	4 months, 7 months and 13 months following Day 0.
Secondary	Change in quality of life- Euro Quality of Life-5-dimension (EQ-5D) questionnaire	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.	4 months, 7 months and 13 months following Day 0.