Evaluation of PPV-06 and Paracetamol in Inflammatory Knee Osteoarthritis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Multicenter Study
- Trial ID
- 2024-514388-24-00
- Protocol
- PPV-06-KOA-201
- Sponsor
- Peptinov
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of PPV-06 on pain and physical function in participants with knee osteoarthritis (OA). This is clinically relevant as knee OA is a prevalent condition that significantly impacts mobility and quality of life, and effective management of pain and improvement in physical function are critical outcomes for patients.
Secondary objectives include:
- Evaluating the efficacy of PPV-06 on key joint features of knee OA.
- Assessing the efficacy of PPV-06 on other symptoms of OA.
- Evaluating the impact of PPV-06 on quality of life.
- Assessing the use of rescue medication during treatment with PPV-06.
- Evaluating the impact of PPV-06 treatment on health economic parameters.
- Evaluating the safety and tolerability of PPV-06.
- Exploring the immune response and development of antibodies to treatment with PPV-06.
Participants
The clinical trial focuses on evaluating the efficacy of PPV-06 on pain and physical function in participants with **knee osteoarthritis**. The study population includes both male and female participants aged 40 years and older. Participants are required to have a body mass index (BMI) between 22 to 35 kg/m². The trial does not involve a vulnerable population. Participants must have a diagnosis of osteoarthritis of the index knee based on the American College of Rheumatology clinical and radiographic criteria, with a Kellgren-Lawrence grade of 2 or 3. Additionally, evidence of moderate to severe synovitis in the index knee is required, as confirmed by ultrasound. The sponsor has not provided information regarding the total number of participants. Participants are expected to have normal liver and renal function and must be willing to discontinue all pain medications for osteoarthritis, except for rescue medication, throughout the clinical trial. The trial population was selected based on specific inclusion criteria, including insufficient pain relief with standard care within six months prior to the screening visit. Lifestyle considerations such as diet and physical activity are not specified in the provided data.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of PPV-06 active immunotherapy in patients with **knee osteoarthritis**. The trial aims to assess the impact of PPV-06 on pain and physical function in participants. The study will involve a total duration of approximately 104 weeks, with the estimated recruitment start date set for February 2025 and an estimated end date in June 2028.
Participants will be randomly assigned to receive either the investigational product, PPV-06, administered as a **subcutaneous injection**, or a matching placebo. The trial will also include the use of **paracetamol** as a rescue medication, administered orally in the form of film-coated tablets. The maximum treatment period for PPV-06 is 84 weeks, while paracetamol can be used for up to 104 weeks.
The sequence of study visits includes an initial screening visit to confirm eligibility based on specific inclusion criteria, such as age, body mass index, and the presence of knee osteoarthritis as per the American College of Rheumatology criteria. Participants must also demonstrate insufficient pain relief with standard care and have evidence of synovitis in the index knee. Following the screening, participants will undergo baseline assessments before randomization. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and adherence to the study protocol. The primary endpoints include the absolute change from baseline to Week 54 in the pain subscale score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the WOMAC physical function subscale score. Secondary endpoints involve changes in synovitis and cartilage thickness over the study duration.
The expected length of participant involvement is up to 104 weeks, with conditions for early termination including non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is structured to ensure rigorous monitoring and data collection to evaluate the investigational product's efficacy and safety comprehensively.
Treatment
The clinical trial involves the evaluation of **PPV-06**, an active immunotherapy, in patients with inflammatory knee osteoarthritis. **PPV-06** is formulated as a **powder for injection** and is administered via **subcutaneous injection**. The active substance in **PPV-06** is **HIS203-CRM197**, a structurally diverse substance. The maximum daily dose is 10 micrograms, with a total maximum dose of 60 micrograms over a treatment period of 84 days. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
As a comparator treatment, **Panodil, filmovertrukne tabletter** is used, which contains the active substance **paracetamol**. This medication is provided in the form of a **film-coated tablet** and is administered **orally**. The maximum daily dose of **Panodil** is 3 grams, with a total maximum dose of 2187 grams over a treatment period of 104 days. The administration of **Panodil** follows standard dosing guidelines, and participant compliance is monitored throughout the trial.
A **matching placebo** is also utilized in this study to maintain the double-blind design. The placebo is designed to mimic the appearance and administration route of the active treatments, ensuring that neither the participants nor the investigators are aware of the treatment allocations. The placebo is administered according to the same schedule as the active treatments, and compliance is similarly monitored.
Efficacy
The efficacy of the investigational product PPV-06 in patients with **knee osteoarthritis** will be assessed through several primary and secondary endpoints. The primary endpoints include the absolute change from baseline to Week 54 in the pain subscale score and the physical function subscale score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). These scores are derived from a 5-item and a 17-item subscale, respectively, and are used to evaluate the impact of the treatment on pain and physical function.
Secondary endpoints will focus on the absolute change from baseline to Week 54 in synovitis, as measured by an 11-point synovitis score. Additionally, the change in cartilage thickness in the medial femorotibial compartment will be assessed at 2 years (Week 104) using MRI and quantitative image analysis methods. These measures will provide further insights into the structural effects of the treatment on the knee joint.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant has given written informed consent to participate.
- Participant male or female.
- Participant aged at least 40 years old.
- Participant has a BMI between 22 to 35kg/m² at Screening visit.
- Participant has a diagnosis of osteoarthritis of the index knee based on American College of Rheumatology (ACR) clinical and radiographic criteria and functional capacity class of I-III, with a Kellgren-Lawrence grade [KLG] 2 or 3.
- Participant has an OARSI medial Joint Space Narrowing (mJSN) Grade 1 or 2 of the index knee joint, confirmed by a semi-flexed or fixed flexion weight-bearing X-Ray performed at Screening visit, and assessed by Central Reader.
- Evidence during the Screening visit of synovitis in the index knee based on ultrasound as described in the Ultrasound manual.
- Evidence of moderate to severe synovitis (≥9 out of 22) on 11-point synovitis score (based on(1), performed during the Screening visit and assessed by Central Reader.
- Participant has insufficient pain relief with standard of care (i.e. non-pharmacological treatments, systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics) for symptomatic OA in the index knee within 6 months prior to the Screening visit.
- Participant must have pain at index knee for the majority of days (>50%) during the preceding month prior to the Screening Visit.
- At Screening Visit 1a, participant reports that their typical OA knee pain in one or both knees when not using medication is ≥ 4 out of 10.
- Participant must have a WOMAC pain subscale score (5 items) in the range [≥4 and ≤8], using the 11-point (0-10) NRS for the index knee at Screening and Baseline visits.
- Participant is willing to discontinue all pain medications for OA except rescue medication (paracetamol), to adhere to the restricted use of concomitant treatments (see Section 6.5) and not use prohibited pain medications throughout the clinical trial.
- Participant with normal liver and renal function defined as: • Serum Alkaline phosphatase levels up to 1.5 of ULN (Upper Limit of Normal). • Serum AST and ALT levels up to 2.5 of ULN. • Serum creatinine levels up to 1.5 of ULN. • Blood Urea Nitrogen levels up to 1.5 of ULN.
- Female participants must be of non-childbearing potential defined as (see Appendix 1): a. Post-menopausal status with cessation of regular menses for at least 12 con-secutive months with no alternative pathological; or physiological cause and have a serum FSH level confirming the post-menopausal state; or b. Undergone a documented total hysterectomy and/or bilateral oophorectomy; or c. Have medically confirmed ovarian failure.
- Male participants agree to refrain from donating sperm and use barrier contraception (con-dom) during sexual intercourse with women of childbearing potential throughout the entire study after randomization and until 5 months after the last IMP administration.. The male participant is willing to ensure that during this period the female sexual partner is addition-ally practicing contraception, if of childbearing potential.
- The Investigator considers that no additional benefit can reasonably be expected from adjustments of current participant’s symptomatic KOA treatment.
Exclusion Criteria
- Participant had an administration of NSAID (topical, tablets) or Cox-2 Inhibitors within 2 weeks prior to the Baseline visit.
- Participant had an injection of either corticosteroid or intra-articular (IA) Visco-supplementation (i.e., hyaluronic acid) into the index knee within 1 month of Screening.
- Participant had an injection of platelet-rich plasma (PRP) into the index knee within 6 months of Screening.
- Participant applied topical capsaicin on the index knee within 1 month of Screening.
- Participant has past joint replacement surgery of the index knee.
- Participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening.
- Participant has a scheduled surgery except dental surgery during the clinical trial period.
- Participant has any known active infection, including suspicion of intra-articular infection, ulcer or open wound anywhere on the index knee.
- Participant has periarticular pain from any cause other than osteoarthritis, including referred pain, bursitis, tendinitis, soft tissue tenderness, or subacute/acute pain from injury in the index knee.
- Participant has known presence of pre-existing MRI-based findings warranting exclusion in accordance with the ROAMES criteria(2), such as rapidly progressing osteoarthritis (RPOA) Type I or Type II, osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, severe bone on bone osteoarthritis, or knee pain attributable to disease other than osteoarthritis, or as assessed by X-Ray based on Central imaging Reading at Screening Visit and before the Baseline Visit.
- Participant has significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the index knee (varus >10°, valgus >10°) by X-Ray as assessed by Central Readers at Screening Visit.
- Participant has other conditions that could affect trial endpoint assessments of the index knee, including, but not limited to, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout or pseudogout, inflammatory bowel disease related arthropathy, peripheral neuropathy (e.g., diabetic neuropathy), lupus erythematosus, significant skin conditions such as abscesses, acromegaly, metabolic joint diseases and fibromyalgia.
- Participant has neuropathic pain as assessed by PainDETECT questionnaire with a score of at least 18 at Screening Visit.
- Participant had systemic (except inhaled) immunosuppressant agent within 6 months prior to trial medication administration.
- Participant has current clinically significant disease(s) or condition(s) (including clinically significant cardiovascular disease and/or significant pain in other areas) that may affect efficacy or safety assessments, or any other reason which, in the investigator’s opinion, may preclude the participant’s participation in the full duration of the trial.
- Participant has a major bleeding disorder encompassing, but not limited to coagulopathy and any current antithrombotic and anticoagulant events.
- Participant has a history of severe allergic or anaphylactic reactions.
- Participant has known or suspected hypersensitivity to or previous hypersensitivity reactions to PPV-06, or any of the excipients in the IMP.
- Participant has a known infection of human immunodeficiency virus (HIV), or known current acute or chronic hepatitis B or C infection.
- Participant has unstable or poorly controlled blood pressure which, in the opinion of the investigator, would put the participant at risk of severe adverse blood pressure increases upon IMP administration.
- Participant has a history of malignancy within 5 years prior to the Screening visit, with the exception of basal cell carcinoma.
- Participant diagnosed with TB are excluded. Participants with a history of either active TB or latent TB may be eligible provided documented written review and approval by a TB-specialist..
- Participant has contraindications to an MRI (including the gadolinium contrast with a Glomerular Filtration Rate (GFR) below 60 mL/min) of the index knee or has a pace-maker or any other implanted electronic devices. Claustrophobic participant with impos-sibility to undergo an MRI.
- Participant has a history of alcohol or drug abuse or was actively abusing drugs (includ-ing alcohol, medication) during the 1 year prior to the Screening Visit as judged by the investigator.
- Participant has evidence or history of severe psychiatric illness/disorder during 3 years prior to the Screening Visit that, in the investigator’s opinion, may affect safety or effi-cacy assessments or may compromise the participant’s safety during trial participation, e.g., major depression, major anxiety disorder, psychosis, severe personality disorders.
- Participant has evidence of cognitive impairment including dementia that may interfere with the participant’s ability to complete participant reported outcomes.
- Participant is known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.
- Participant is not able to communicate meaningfully with the trial site staff.
- Participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit.
- Participant is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site or is a family member of the employees or the investigator.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Yet Recruiting | 01 Feb 2025 | 40 |
 Denmark | Not Yet Recruiting | 01 Feb 2025 | 50 |
 France | Not Yet Recruiting | 01 Feb 2025 | 44 |
 Poland | Not Yet Recruiting | 01 Feb 2025 | 50 |
 Romania | Not Yet Recruiting | 01 Feb 2025 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Panodil, filmovertrukne tabletter | Other | FILMOVERTRUKNE TABLETTER | ORAL | 3 | 104 | PRD305299 |
PPV-06 | Test | POWDER FOR INJECTION | SUBCUTANEOUS INJECTION | 10 | 84 | PRD8236519 |
Matching Placebo | Placebo | N/A | — | — | — | N/A |