A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof of Concept Trial to Investigate the Efficacy and Safety of Intra-articular 4P004 in Subjects With Knee Synovitis and Osteoarthritis
This phase 2a trial is an international, multicenter, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of one single intra-articular (IA) injection of 4P004 or placebo in: * patients between 40 and 80 years of age, * with synovitis and grade 2 to 4 osteoarthritis (OA) of the knee according to Kellgren and Lawrence (KL) classification.
• Participants who have the capacity to give informed consent and who are willing to comply with all trial related procedures and assessments.
• Participants between 40 and 80 years of age.
• Female participant of childbearing potential (defined as any woman unless postmenopausal for at least one year or surgically sterile) must use highly effective methods of contraception as defined in the protocol. Highly effective contraceptive measures must be continued throughout the trial until the final visit.
• Bodyweight \> 40 kg.
• Body mass index (BMI) ≥ 18.5 and ≤ 35.
• Ambulatory (single assistive devices such as canes allowed).
• Widespread Pain Index (WPI) ≤ 4.
• Pain NRS (0-10) \< 4 in the contralateral knee.
• History of OA-related pain of the TK for at least 6 months.
• Moderate to severe pain of the TK the majority of days during the last 3 months as per participant's judgement.
• Moderate to severe pain of the TK on the WOMAC Pain subscale prior to the Randomization visit (V2) complying with: a) Complete WOMAC Pain diary for at least 7 of the last 10 days prior to V2 (including V2/D1 rating which is mandatory), and b) Diary reported WOMAC Pain between 5 and 9 for at least 7 of the last 10 days.
• History of insufficient pain relief, intolerance, or contraindication to NSAIDs, and at least a history of insufficient pain relief from at least one of the following therapies: a) Acetaminophen/paracetamol, b) Opioids including tramadol, or c) Corticosteroids, hyaluronate IA injections (efficacy less than 3 months according to the patient).
• KL grade 2 to 4 on the Schuss radiograph.
• Predominant femorotibial OA based on the OA Research Society International. (OARSI) Atlas reading (Altman \& Gold, 2007).
• Presence of synovitis in the TK assessed locally using PDUS, and synovial thickness of ≥ 5 mm evaluated through a longitudinal view of the suprapatellar pouch and axial views of the medial and lateral patellofemoral pouches.
• Negative urine drug screen (performed locally): amphetamines, barbiturates, cocaine.
• CE-MRI Central reading to confirm synovitis with a synovial Semi-Quantitative (SQ) ≥ 9 or a SQ score ≥7 with at least one site with a score ≥ 2.