Knee OsteoarthritisPhase 1NCT06463132
Phase 1b Clinical Trial to Evaluate PEP and EUFLEXXA for Knee Osteoarthritis (KOA)
A Phase 1 study testing PEP/Euflexxa and PEP in people with Knee Osteoarthritis, run by Rion Inc. at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- PEP/Euflexxa and PEP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2024to 1 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- Steroid or viscosupplement injection in the planned treatment knee(s) within the past 3 months.
- PRP injection in the planned treatment knee(s) within the past 6 months.
- History of documented allergy to intra-articular EUFLEXXA.
- History of cancer including melanoma (with the exception of localized skin cancer) in the past 2 years.
- HIV positive participants.
- BMI > 40 kg/m2.
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- Arthroscopic debridement in the planned treatment knee(s) in the last 6 months.
- Cartilage restoration procedure in the planned treatment knee(s) in the last 5 years.
- History of gout or pseudogout.
- History of or evidence of active rheumatologic disease, severe peripheral neuropathy, clinically evident cardiac or respiratory disease that interferes with functional status.
- Poorly controlled diabetes defined as a glycated hemoglobin (HbA1c) concentration of ≥ 8.0%.
- Currently taking any cancer treatment regimen (including aromatase inhibitors).
- Calcium pyrophosphate deposition disease (CPPD) evident on X-ray.
- Systemic (oral, intravenous, or intramuscular) steroids in the last 3 months.
- Concurrent participation in another investigational drug or device study or participation in the last 30 days prior to enrollment.
- Evidence of recent alcohol or drug abuse, or history of medication misuse or addiction.
- Female participants who are pregnant, breast feeding, or trying to become pregnant.
- Women unwilling to use approved contraception method for 3 months after receiving dose of investigational drug.
- Unwilling or unable to comply with Telehealth visits (eg, ability to access internet, on camera capabilities, etc).
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Phase 1b Open-Label, Multi-Center, Randomized Trial to Evaluate the Safety of PEP and EUFLEXXA for the Treatment of Subjects With Knee Osteoarthritis (KOA)
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
Read the 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).
- Conditions
- Knee Osteoarthritis
- Being tested
- PEP/Euflexxa, PEP
- Keywords
- Knee Osteoarthritis, Exosome, Osteoarthritis, Joint Disease, Hyaluronic Acid, Extracellular Vesicle, Musculoskeletal Diseases, Arthritis, Randomized Clinical Trial, Rheumatic Diseases, Osteoarthritis, Knee, Biologic
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis, Joint Diseases, Musculoskeletal Diseases, Arthritis, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEP/EuflexxaCombination product
Euflexxa (PMA: P010029)
PEPDrug
PEP (Purified Exosome Product)
| Study group | Role | What they receive |
|---|---|---|
| 1A PEP Low Dose | Experimental | 1A PEP Low Dose in Saline Receives: Drug: PEP |
| 1B PEP High Dose | Experimental | 1B PEP High Dose in Saline Receives: Drug: PEP |
| 2a PEP-EUFLEXXA Low Dose | Experimental | 2A PEP-EUFLEXXA Low Dose Receives: Combination Product: PEP/Euflexxa |
| 2b PEP-EUFLEXXA High Dose | Experimental | 2B PEP-EUFLEXXA High Dose Receives: Combination Product: PEP/Euflexxa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Safety Follow up 90 Days post injection occurrence of DLTs
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).
Measured: First 90 days
Long Term Safety Follow-Up Occurrence of DLTs From Day 91 to 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.
Measured: Day 365
Secondary outcomes (2)
Exploratory Endpoints of Efficacy-Radiographic Response
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
Measured: Day 365
Exploratory Endpoints of Efficacy-Participant-Reported responses:
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.
Measured: Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2024
- Study start1 Nov 2024 (estimated)
- Primary completion1 Nov 2025 (estimated)
- Study completion1 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Arm 1A, PEP Low Dose Arm 1B, PEP High Dose Arm 2A, PEP-EUFLEXXA Low Dose Arm 2B, PEP-EUFLEXXA High Dose
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rion Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Caidya Clinical Research Organization
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06463132
- Sponsor's protocol ID
- PRO-00126
- Status last verified
- Jun 2024
- First submitted
- 7 Jun 2024
- Last updated
- 17 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Open-Label, Multi-Center, Randomized Trial to Evaluate the Safety of PEP and EUFLEXXA for the Treatment of Subjects With Knee Osteoarthritis (KOA)
- ClinicalTrials.gov ID
- NCT06463132
- Acronym / sponsor ID
- PRO-00126
- Conditions
- Knee Osteoarthritis
- Keywords
- Knee Osteoarthritis, Exosome, Osteoarthritis, Joint Disease, Hyaluronic Acid, Extracellular Vesicle, Musculoskeletal Diseases, Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Rion Inc.Industry (pharma, biotech, devices)
- Collaborators
- Caidya Clinical Research Organization
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 1 Nov 2025 (estimated)
- Study completion
- 1 Nov 2025 (estimated)
- First posted
- 17 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Arm 1A, PEP Low Dose Arm 1B, PEP High Dose Arm 2A, PEP-EUFLEXXA Low Dose Arm 2B, PEP-EUFLEXXA High Dose
| Arm | Type | Receives |
|---|---|---|
| 1A PEP Low Dose | Experimental | Drug: PEP1A PEP Low Dose in Saline |
| 1B PEP High Dose | Experimental | Drug: PEP1B PEP High Dose in Saline |
| 2a PEP-EUFLEXXA Low Dose | Experimental | Combination Product: PEP/Euflexxa2A PEP-EUFLEXXA Low Dose |
| 2b PEP-EUFLEXXA High Dose | Experimental | Combination Product: PEP/Euflexxa2B PEP-EUFLEXXA High Dose |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age: Adults aged 18-90 years of age
- 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:
Key exclusion criteria (19 listed)
- Steroid or viscosupplement injection in the planned treatment knee(s) within the past 3 months.
- PRP injection in the planned treatment knee(s) within the past 6 months.
- History of documented allergy to intra-articular EUFLEXXA.
- History of cancer including melanoma (with the exception of localized skin cancer) in the past 2 years.
- HIV positive participants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PEP/EuflexxaEuflexxa (PMA: P010029) | Combination product | 2a PEP-EUFLEXXA Low Dose, 2b PEP-EUFLEXXA High Dose |
| PEPPEP (Purified Exosome Product) | Drug | 1A PEP Low Dose, 1B PEP High Dose |
Primary outcome
Primary Safety Follow up 90 Days post injection occurrence of DLTs
Time frame: 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
Time frame: 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.
2 secondary outcomes
Exploratory Endpoints of Efficacy-Radiographic Response
Time frame: Day 365
Exploratory Endpoints of Efficacy-Participant-Reported responses:
Time frame: Day 365
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PEP/Euflexxa and PEP in people with Knee Osteoarthritis, run by Rion Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shariq Khan, M.S. (847-702-4063, khan@riontx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Safety Follow up 90 Days post injection occurrence of DLTs (time frame: First 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2024.