Primary Knee Osteoarthritis
Conditions
Keywords
Knee, Osteoarthritis, Allocetra
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled, Phase IIb study to evaluate intra-articular (IA) injections of Allocetra in participants with moderate-to-severe age related symptomatic primary knee osteoarthritis (OA).
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. The main goal of this Phase IIb clinical trial is to evaluate the efficacy of intra-articular (IA) injections of Allocetra in participants with moderate-to-severe age related symptomatic primary knee osteoarthritis (OA), in comparison to Placebo (a look-alike substance that contains no drug). Participants will be randomized 1:1 to Allocetra or Placebo. Treatment consists of a total of three ultrasound-guided intra-articular (IA) injections (Days 0, 14, 28). Follow-up will continue for 12 months.
Interventions
DRUGAllocetra
Allocetra is a cell-based therapy consisting of non-HLA-matched allogeneic peripheral blood mononuclear cells, induced to an apoptotic stable state.
OTHERPlacebo
The control used in this study will be placebo. Placebo solution containing all excipients except for the Allocetra cells.
Sponsors
Enlivex Therapeutics Ltd.
Nordic Bioscience Clinical Development (NBCD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
64 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the inclusion criteria listed below to be eligible for the study: 1. Age 64 years or above. 2. Diagnosis of primary femorotibial knee OA. 3. Radiographic evidence of knee OA defined as Kellgren-Lawrence (KL) grade 2 or 3 in the index knee. 4. Participants who are intolerant to, or have failed to adequately respond to at least 2 OA therapies. 5. Index knee pain assessed during the screening period and following wash-out of pain medications. 6. Willingness to abstain from prohibited medications/treatments during the trial. 7. Women who are postmenopausal (≥12 months natural amenorrhea without alternative cause) or surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). 8. Male participants with partners of childbearing potential, who are not surgically sterile (vasectomy) for at least 6 months prior to randomization, must use condoms with spermicide in addition to their partner's contraception from randomization and for 90 days after last dose.
Exclusion criteria
Participants will be excluded from the study if they meet any of the following criteria: 1. Severe or end-stage osteoarthritis of the index knee. 2. Clinically significant structural abnormalities or instability of the index knee. 3. Recent major injury, surgical procedure, or intra-articular treatment in the index knee. 4. Any known history of infection or tumor of the index knee, or active infection at the intended injection site. 5. Any known history of inflammatory arthropathy or crystal-deposition disease. 6. Any severe systemic cartilage, bone, or musculoskeletal disorder that may interfere with study outcomes. 7. Clinically significant widespread pain syndromes. 8. Immunosuppressive therapy, clinically significant immunodeficiency, or active infection. 9. Body Mass Index (BMI) \>40 kg/m² 10. Use of medications that may interfere with pain assessment or study outcomes. 11. Known coagulopathy or use of anticoagulant/antiaggregant medication. 12. Significant uncontrolled systemic disease or clinically significant findings on screening laboratory tests or physical examination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain score at 3 months | 3 months. | The change from baseline of the WOMAC Pain score at 3 months between Allocetra and Placebo. Total Pain score ranges from 0 (No pain) to 50 (Extreme pain). |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function score at 3 months | 3 months. | The change from baseline for the WOMAC Function score at 3 months between Allocetra and Placebo. Total Function score ranges from 0 (No difficulty) to 170 (Extreme difficulty). |
| Primary Safety Endpoint | Day 0 to 6 months. | Incidence and severity of Adverse Events (AEs) up to 6 months. AE incidence will be represented as % per study group and AE severity will be represented as mild, moderate or severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain score | 6 months. | The change from baseline of the WOMAC Pain score at 6 months. Total Pain score ranges from 0 (No pain) to 50 (Extreme pain). |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function score | 6 months. | The change from baseline of the WOMAC Function score at 6 months. Total Function score ranges from 0 (No difficulty) to 170 (Extreme difficulty). |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total score | 3 months, 6 months. | The change from baseline for the WOMAC Total score at 3 and 6 months. Total score ranges from 0 to 240 when higher score means worse outcomes. |
| Average Daily Pain Numerical Rating Scale (ADP-NRS) | 3 months, 6 months. | The change from baseline of the Average Daily Pain Numerical Rating Scale (ADP-NRS) at 3 and 6 months. ADP-NRS score ranges from 0 (No pain) to 10 (Worst imaginable pain). |
| Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) score | 3 months, 6 months. | Treatment responders at 3 and 6 months according to the Outcome Measures in Rheumatology (OMERACT) and Osteoarthritis Research Society International (OARSI) criteria. OMERACT-OARSI score will be represented as % when higher scores means a better outcome. |
| Euro Quality of Life-5-Dimension (EQ-5D) index scores | 3 months, 6 months. | Change from baseline in Euro Quality of Life-5-Dimension (EQ-5D) index scores at 3 and 6 months. EQ-5D index scores in composed of an index value which range from 0 to 1 and EQ VAS score which range from 0 to 100. In both a higher score means better outcomes. |
Countries
Denmark, Poland, United States
Contacts
CONTACTLior Binder
CONTACTLital Weinfeld Bergman
STUDY_DIRECTORLital Weinfeld Bergman
Senior Director of Clinical Operations
Outcome results
None listed