DRUG
4P004
Single intra-articular injection in the knee joint
Status
Active, not recruiting
Phase
Phase 2
Enrollment
129
Locations
22
Results
Not posted
Publications
0
Study summary
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.
Interventions
DRUG
Single intra-articular injection in the knee joint
DRUG
Single intra-articular injection in the knee joint
Timeline
First posted
Nov 10, 2025
Study start
Jun 17, 2025
Primary completion
Aug 28, 2026
Study completion
Sep 2026
Results posted
Not reported
Registry updated
Jul 27, 2026
Outcomes
Change from Baseline at Week 4 in the weekly average of Target Knee (TK) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore
Time frame · Baseline and Week 4
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Change from Baseline at Week 2, Week 6, Week 8, Week 10 and Week 12 in the weekly average of TK (Target Knee) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore
Time frame · Baseline, Week 2, Week 6, Week 8, Week 10 and Week 12
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the NRS (Numeric Rating Scale) pain (scale 0-10) in a nominated pain aggravating activity
Time frame · Baseline, Week 2, Week 4, Week 8 and Week 12
The numeric rating scale (NRS) is a pain screening tool, commonly used to assess pain severity at that moment in time, using a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable.
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in WOMAC (Western Ontario and McMaster Universities Arthritis Index) subscores and total score
Time frame · Baseline, Week 2, Week 4, Week 8 and Week 12
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the Patient Global Assessment of Osteoarthritis (PGA-OA)
Time frame · Baseline, Week 2, Week 4, Week 8 and Week 12
The PGA-OA is a 1-item questionnaire designed to assess the participant's impression of disease severity adapted from Guy et al., 1976, to the specific disease as a Patient-reported Outcome measurement "Considering all the ways your knee osteoarthritis affects you, how are you doing these last seven days ?". PGA-OA is measured on a 5-point Likert scale, with higher scores indicating worse symptoms (1= "very good" to 5 = "very poor").
Percentage (%) of OMERACT-OARSI Responders at Week 2, Week 4, Week 8 and Week 12
Time frame · Week 2, Week 4, Week 8 and Week 12
Incidence and severity of TEAEs (Treatment-Emergent Adverse Events) during the trial
Time frame · From randomization to end of trial, up to 12 weeks
Absolute changes from Baseline in clinical laboratory assessment - hematology parameter: total blood cells count (in cell/L)
Time frame · From randomization to end of trial (up to 12 weeks)
Absolute changes from Baseline in clinical laboratory assessments - hematology parameter: hemoglobin (in g/L)
Time frame · From randomization to end of trial (up to 12 weeks)
Absolute changes from Baseline in clinical laboratory assessment - blood chemistry: AST (in U/L)
Time frame · From randomization to end of trial (up to 12 weeks)
Absolute changes from Baseline in clinical laboratory assessment - blood chemistry: ALT (in U/L)
Time frame · From randomization to end of trial (up to 12 weeks)
Eligibility
Inclusion Criteria: * 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. Exclusion Criteria: * Pregnant or breastfeeding women. * Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the TK (varus \> 10°, valgus \> 10°) by radiography. * Secondary OA such as joint dysplasia, aseptic osteonecrosis, joint infection, acromegaly, Paget disease, hemochromatosis, joint crystal disease or any inflammatory joint disease. * Any known active infections including skin infections at the site injection or increased predisposition for the development of infections. * Any partial knee replacement of the TK. * Acute fracture or IA trauma to the TK within 12 months prior to the screening visit. * Major knee surgery performed within the previous 12 months or planned during the trial. * Arthroscopy of the TK within 6 months prior to the screening visit. * Presence of any painful conditions that could confound accurate assessment of pain from OA in the TK, such as fibromyalgia, peripheral neuropathy or vascular insufficiency. * Treatment with systemic corticosteroids (other than IA) at a dose greater than 10 mg prednisone or the equivalent per day for more than 7 days within 4 weeks prior to the screening visit. * Treatment of the TK with any IA injection (including corticosteroids, hyaluronic acid derivatives, Platelet Rich Plasma….) within 24 weeks prior to the screening visit. * Any treatment with glucosamine, chondroitin sulfate, or other nutraceuticals with potential activity on OA within the previous 3 months prior to the screening visit. * Treatment with duloxetine for OA (allowed if given for depressive disorders at stable dose since at least 3 months before V1). * Any significant psychiatric illness unless well controlled since at least 6 months. * Current treatment with combination of insulin and liraglutide (Xultophy®) or with GLP-1 agonist administered once a week (semaglutide, dulaglutide). * High-risk of bleeding. * Congestive Heart Failure stage III or IV in the New York Heart Association classification. * History or current diagnosis of electrocardiogram ECG abnormalities indicating significant safety risk (such as ischemia, significant cardiac arrhythmias). * Glycemia \< 4.4 mmol/L (or 80 mg/dL) at screening. * Clinically significant abnormal laboratory test at screening, in particular: haemoglobin \<10 g/dL, white blood cell \<3000/µL (3.0 Giga/L), absolute neutrophil count \<1000/µL (1.0 Giga/L), platelets count \<100,000/µL (100 Giga/L), alanine aminotransferase or aspartate aminotransferase \>2.5 upper limit of normal (ULN), total bilirubin \>1.5 ULN, lipasemia \>1 ULN. * Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2, using Chronic Kidney Disease - EPIdemiology (CKD EPI) 2021 Formula. * Any other abnormal laboratory results that the Investigator believes should preclude the subject's participation in the trial. * History of hypersensitivity to IMP or excipients (liraglutide or disodium phosphate dihydrate, propylene glycol, phenol). * Any contraindication for MRI (cardiac pacemaker, deep brain stimulators, intraocular metal, cerebral aneurysm clips, recent stents, cochlear implants, neurostimulators and implantable pumps) or inability to undergo MRI (e.g., body size, leg not fitting in the coil, claustrophobia). * History of hypersensitivity reactions to a gadolinium-based contrast agent. * Any CE-MRI Central reading additional diagnoses: posterior meniscal root tears, subchondral insufficiency fractures, osteonecrosis, malignant bone marrow infiltration, solid tumours, and traumatic fracture or bone bruise using ROAMES (Roemer et al., 2020). * Previous participation in clinical research with a disease-modifying OA drug during the last 2 years. * Participation in an interventional clinical research trial within 3 months before screening. * Participants who, in the investigator's judgement, are at risk of falling. * Participants with a history, or current diagnosis, of pancreatitis, thyroid cancer (including medullary thyroid carcinoma), multiple endocrine neoplasia type-2 (MEN2), diabetic ketoacidosis, type-1 diabetes mellitus (T1DM), inflammatory bowel disease, or diabetic gastroparesis. * Participants currently, or within the last 10 days, taking any anticoagulant treatment.
Study locations
Canada · Denmark · France · Poland · Spain · United States. Showing up to 24 locations stored in the fast local snapshot.
Tucson Orthopaedic Institute
Tucson, Arizona, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
Skylight Health Research Burlington
Burlington, Massachusetts, United States
Durham Bone and Joint Specialists
Ajax, Canada
SJHC London Rheumatology Centre
London, Canada
G.R.M.O. (Groupe de recherche en maladies osseuses) Inc
Québec, Canada
Parker Institute Bispebjerg, Frederiksberg Hospital
Frederiksberg, Denmark
Sanos Clinic Herlev
Herlev, Denmark
CHU Montpellier
Montpellier, France
ChU de Nice
Nice, France
Hôpital Cochin
Paris, France
Hôpital Lariboisière
Paris, France
Centre Hospitalier Universitaire CHU de Reims - Hopital Maison Blanche
Reims, France
Care Access Kraków
Krakow, Poland
Centrum Medyczne Reuma Park
Warsaw, Poland
MICS Centrum Medyczne Warszawa
Warsaw, Poland
Clínica Gaias Santiago
A Coruña, Spain
Complejo Hospitalario Universitario de A Coruna - Hospital Universitario de A Coruna
A Coruña, Spain
HLA Clínica Vistahermosa
Alicante, Spain
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
Sabadell, Spain
Clinica Nuestra Senora de la Esperanza
Santiago de Compostela, Spain
Hospital Quirónsalud Sagrado Corazón
Seville, Spain
Publications
No PMID-linked publications were present in this registry snapshot.
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