HIS203-CRM197 for Knee osteoarthritis

Inclusion criteria

• {"criterion_text":"- Participant has given written informed consent to participate.\n- Participant must have pain at index knee for the majority of days (>50%) during the preceding month prior to the Screening Visit.\n- 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.\n- 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.\n- 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.\n- Participant with normal liver and renal function defined as: •\tSerum Alkaline phosphatase levels up to 1.5 of ULN (Upper Limit of Normal). •\tSerum AST and ALT levels up to 2.5 of ULN. •\tSerum creatinine levels up to 1.5 of ULN. •\tBlood Urea Nitrogen levels up to 1.5 of ULN.\n- 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.\n- 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.\n- The Investigator considers that no additional benefit can reasonably be expected from adjustments of current participant’s symptomatic KOA treatment.\n- Participant male or female.\n- Participant aged at least 40 years old.\n- Participant has a BMI between 22 to 35kg/m² at Screening visit.\n- 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.\n- 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.\n- Evidence during the Screening visit of synovitis in the index knee based on ultrasound as described in the Ultrasound manual.\n- 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.\n- 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."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Absolute change from baseline to Week 54 of the pain subscale score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (5 items)","definition_or_measurement_approach":"Change from baseline to Week 54 measured using the WOMAC pain subscale (5 items) using the 11-point NRS (0-10) for the index knee."}
• {"endpoint_text":"- Absolute change from baseline to Week 54 of the WOMAC physical function subscale score (17 items)","definition_or_measurement_approach":"Change from baseline to Week 54 measured using the WOMAC physical function subscale (17 items)."}

Secondary endpoints

• {"endpoint_text":"- Absolute change from baseline to Week 54 of Synovitis based on 11-point synovitis score","definition_or_measurement_approach":"Change from baseline to Week 54 measured by an 11-point synovitis score (central reader assessment)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change from baseline in cartilage thickness in the medial femorotibial compartment assessed by MRI at Week 104 using a quantitative image analysis method (central assessment)."}

Czechia

Earliest CTIS Part Ii Submission Date

05-11-2024

Latest Decision Or Authorization Date

06-03-2025

Processing Time Days

121

Number Of Sites

6

Number Of Participants

40

Denmark

Earliest CTIS Part Ii Submission Date

21-11-2024

Latest Decision Or Authorization Date

13-02-2025

Processing Time Days

84

Number Of Sites

3

Number Of Participants

50

France

Earliest CTIS Part Ii Submission Date

03-10-2024

Latest Decision Or Authorization Date

13-02-2025

Processing Time Days

133

Number Of Sites

4

Number Of Participants

44

Romania

Earliest CTIS Part Ii Submission Date

04-09-2024

Latest Decision Or Authorization Date

07-04-2025

Processing Time Days

215

Number Of Sites

3

Number Of Participants

20

Poland

Earliest CTIS Part Ii Submission Date

08-11-2024

Latest Decision Or Authorization Date

02-03-2025

Processing Time Days

114

Number Of Sites

6

Number Of Participants

50

Primary sponsor

Full Name

Peptinov

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"Germany","full_name":"Nexelis Marburg GmbH","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Laboratories","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Health care"}
• {"country":"Denmark","full_name":"NBCD A/S","duties_or_roles":"sponsorDuties codes: [\"1\",\"11\",\"12\",\"13\",\"2\",\"3\",\"5\",\"6\",\"7\",\"8\"]","organisation_type":"Pharmaceutical company"}