Knee Osteoarthritis
Conditions
Keywords
Knee Osteoarthritis, Exosome, Osteoarthritis, Joint Disease, Hyaluronic Acid, Extracellular Vesicle, Musculoskeletal Diseases, Arthritis, Randomized Clinical Trial, Rheumatic Diseases, Osteoarthritis, Knee, Biologic
Brief summary
Evaluate the safety and exploratory efficacy of single intra-articular injections of PEP reconstituted with 0.9% Normal Saline at a low dose (one vial PEP) and high dose (two vials PEP), with and without EUFLEXXA, for the treatment of Knee Osteoarthritis
Detailed description
Study Plan (with Dose Escalation): Arm 1 and Arm 2 will run in parallel such that initially 3 subjects will be enrolled in Arm 1a (PEP Low Dose) and 3 subjects will be enrolled in Arm 2a (PEP-EUFLEXXA Low Dose). After all 6 subjects complete the 30 day follow up and there was not more than 1 AE grade 3 or higher per Arm, a further 9 subjects will be enrolled in Arm 1b (PEP High Dose) and a further 9 subjects will be enrolled in Arm 2b (PEP-EUFLEXXA High Dose).
Interventions
COMBINATION_PRODUCTPEP/Euflexxa
Euflexxa (PMA: P010029)
DRUGPEP
PEP (Purified Exosome Product)
Sponsors
Caidya Clinical Research Organization
Rion Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arm 1A, PEP Low Dose Arm 1B, PEP High Dose Arm 2A, PEP-EUFLEXXA Low Dose Arm 2B, PEP-EUFLEXXA High Dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
• Age: Adults aged 18-90 years of age Type of Participant and Disease Characteristics: * Diagnosis of unilateral or bilateral symptomatic KOA of at least 6 months duration (meets American College of Rheumatology/Arthritis \[ACR\] criteria) * Daily knee pain in the more symptomatic knee of ≥ 30 and ≤ 80 on a 100-point VAS for greater than 6 months * Kellgren Lawrence Grade 2 to 3 osteoarthritis in the more symptomatic knee based on standard knee radiographs * Failed conservative management including at least 2 of the following: * Lack of improvement with attempted weight loss in the past year if body mass index (BMI) \> 30 kg/m2; * Lack of response to a 4-week trial in the past year of oral acetaminophen or NSAIDs taken as needed; * Lack of response to a 4-week trial in the past year of topical NSAIDs or capsaicin applied as needed; * Lack of improvement after injection therapy with cortisone, PRP or hyaluronic acid; * Lack of improvement after a 4-week course of physical therapy in the past year; or * Lack of improvement after a 4-week trial of quadriceps strengthening home exercise program in the past year. * Requesting injection therapy for pain management * Contraceptive use by participants and their partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. o A serum pregnancy test (human chorionic gonadotropin \[hCG\]) should be done for all women of childbearing potential (WOCBP) at Screening, and a urine pregnancy test should be done on Day 1, prior to injection, with results reviewed before injection to confirm the participant's eligibility. Participants who have positive pregnancy test result will not be permitted to continue in the study (see Section 5.2,
Exclusion criteria
18 and 19). * Signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * Ability to comply with protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Follow up 90 Days post injection occurrence of DLTs | First 90 days | The safety of a single intra-articular injection of PEP, with or without EUFLEXXA, through the initial 90-day treatment period as assessed by the occurrence of DLTs with severity grading based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE). |
| Long Term Safety Follow-Up Occurrence of DLTs From Day 91 to Day 365 | Day 365 | The long-term safety after treatment with a single intra-articular injection of PEP, with or without EUFLEXXA as assessed from the incidence of DLTs during the Day 91 through Day 365 follow up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoints of Efficacy-Radiographic Response | Day 365 | Radiographic response, evaluated pre- and post-injection by an independent, blinded radiologist's assessment: Decrease or lack of progression of cartilage damage (thickness, denudation) and/or bone marrow edema on magnetic resonance imaging (MRI) at 6 or 12 months after injection Decrease or lack of progression in joint space narrowing on weight bearing X ray at 12 months after injection |
| Exploratory Endpoints of Efficacy-Participant-Reported responses: | Day 365 | Clinical improvement measured using a 100 point pain visual analogue scale (VAS) and modified Western Ontario and McMasters University Arthritis Index Questionnaire (WOMAC), which utilizes measures of pain and function, and treatment success based on Osteoarthritis Research Society International Outcome Measures in Rheumatology (OARSI OMERACT) responder criteria defined as follows: Absolute change of 20 points or more on the VAS 100-point scale; or Improvement of 50% of more in the modified WOMAC pain or function score; or Absolute change of 20 points or more in the combined modified WOMAC pain and function score. |
Countries
United States
Contacts
Primary ContactShariq Khan, M.S.
Backup ContactMaureen Merrifield, Ph.D.
Outcome results
None listed