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Single intra-articular 4P004 injection for knee osteoarthritis with synovitis

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

Phase 2 Interventional 4Moving Biotech · NCT07225829

This phase 2a trial tests whether a single injection of 4P004 into the knee can reduce pain and inflammation in adults 40–80 with knee osteoarthritis and synovitis.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment129 (estimated)
Ages40 Years to 80 Years
SexAll
Sponsor4Moving Biotech Industry-sponsored
Drugs / interventionsprednisone
Locations22 sites (Tucson, Arizona and 21 other locations)
Trial IDNCT07225829 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled phase 2a trial comparing one intra-articular injection of 4P004 to saline placebo in adults with knee osteoarthritis and synovitis. Eligible participants are 40–80 years old with Kellgren-Lawrence grade 2–4 OA and clinical evidence of synovitis, and must meet BMI and pain criteria. Sites in the United States will screen, randomize, and follow participants for safety and signs of clinical improvement after a single injection. Study procedures include baseline assessments, the injection visit, and scheduled follow-up visits to measure pain, function, and adverse events.

Who should consider this trial

Good fit: Adults aged 40–80 with KL grade 2–4 knee osteoarthritis and documented synovitis who have had moderate to severe knee pain for at least six months and meet the trial's BMI, weight, and safety criteria.

Not a fit: Patients without synovitis, with KL grade outside 2–4, outside the 40–80 age range, with BMI <18.5 or >35, or with significant comorbidities are unlikely to benefit or may be ineligible.

Why it matters

Potential benefit: If successful, a single 4P004 injection could reduce knee pain and inflammation and offer a longer-lasting, low-burden treatment option for people with OA-related synovitis.

How similar studies have performed: Other intra-articular biologic and steroid injections have shown mixed results, and single-dose biologic approaches like 4P004 remain relatively novel with limited phase 2 evidence.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Tucson, Arizona and 21 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Knee OsteoarthritisSynovitis of KneeOAKnee OALiraglutideOsteoarthritis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.