A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of PPV-06 Active Immunotherapy in Patients with Inflammatory Knee Osteoarthritis (KOA).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Peptinov

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2024-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of PPV-06 on pain and physical function in participants with knee OA.

Secondary objectives 7

1. To evaluate the efficacy of PPV-06 on key joint features of knee OA
2. To evaluate the efficacy of PPV-06 on other symptoms of OA
3. To evaluate the efficacy PPV-06 on Quality of Life
4. To evaluate the use of rescue medication during treatment with PPV-06
5. To evaluate the impact of PPV-06 treatment on health economic parameters
6. To Evaluate the Safety and Tolerability of PPV-06
7. To explore the immune response and development of antibodies to treatment with PPV-06

Conditions and MedDRA coding

Knee osteoarthritis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Data obtained through this study may be provided to qualified researchers on request in accordance with international principles for responsible research (under the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA)). Approval of the request (including e.g. research proposal and statistical analysis plan) and execution of all applicable agreements (i.e. a data sharing agreement) are prerequisites to the sharing of data with the requesting party. Data will only be shared in encoded form to protect participant identity and with requirements for data protection as well as requirements against unauthorized use and disclosure. Participant identity will remain confidential. Participants can inquire about data transfers and security measures at any time by contacting the trial physician.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Participant has given written informed consent to participate.
2. Participant male or female.
3. Participant aged at least 40 years old.
4. Participant has a BMI between 22 to 35kg/m² at Screening visit.
5. 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.
6. 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.
7. Evidence during the Screening visit of synovitis in the index knee based on ultrasound as described in the Ultrasound manual.
8. 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.
9. 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.
10. Participant must have pain at index knee for the majority of days (>50%) during the preceding month prior to the Screening Visit.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. The Investigator considers that no additional benefit can reasonably be expected from adjustments of current participant’s symptomatic KOA treatment.

Exclusion criteria 30

1. Participant had an administration of NSAID (topical, tablets) or Cox-2 Inhibitors within 2 weeks prior to the Baseline visit.
2. 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.
3. Participant had an injection of platelet-rich plasma (PRP) into the index knee within 6 months of Screening.
4. Participant applied topical capsaicin on the index knee within 1 month of Screening.
5. Participant has past joint replacement surgery of the index knee.
6. Participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening.
7. Participant has a scheduled surgery except dental surgery during the clinical trial period.
8. Participant has any known active infection, including suspicion of intra-articular infection, ulcer or open wound anywhere on the index knee.
9. 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.
10. 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.
11. 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.
12. 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.
13. Participant has neuropathic pain as assessed by PainDETECT questionnaire with a score of at least 18 at Screening Visit.
14. Participant had systemic (except inhaled) immunosuppressant agent within 6 months prior to trial medication administration.
15. 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.
16. Participant has a major bleeding disorder encompassing, but not limited to coagulopathy and any current antithrombotic and anticoagulant events.
17. Participant has a history of severe allergic or anaphylactic reactions.
18. Participant has known or suspected hypersensitivity to or previous hypersensitivity reactions to PPV-06, or any of the excipients in the IMP.
19. Participant has a known infection of human immunodeficiency virus (HIV), or known current acute or chronic hepatitis B or C infection.
20. 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.
21. Participant has a history of malignancy within 5 years prior to the Screening visit, with the exception of basal cell carcinoma.
22. 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..
23. 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.
24. 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.
25. 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.
26. Participant has evidence of cognitive impairment including dementia that may interfere with the participant’s ability to complete participant reported outcomes.
27. 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.
28. Participant is not able to communicate meaningfully with the trial site staff.
29. Participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit.
30. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Absolute change from baseline to Week 54 of the pain subscale score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (5 items)
2. Absolute change from baseline to Week 54 of the WOMAC physical function subscale score (17 items)

Secondary endpoints 2

1. Absolute change from baseline to Week 54 of Synovitis based on 11-point synovitis score
2. Absolute change from baseline in cartilage thickness (ThC) in the medial femorotibial compartment (MFTC), assessed by MRI at 2 years (Week 104) using quantitative image analysis method

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Peptinov

Sponsor organisation

Peptinov

Address

42 Rue De Maubeuge

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Peptinov

Contact name

Edita Dolimier

Public contact point

Organisation

Peptinov

Contact name

Bruno Pitrosky

Third parties 4

Locations

5 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications