A Trial to Investigate the Safety and Efficacy of Intra-articular 4P004 Injection in Subjects With Knee Synovitis and Osteoarthritis

NCT07225829 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 4MB-4P004-P-INFLAM2024-518916-38-00
• Study Type: interventional
• Target: 129
• Locations: 6 countries
• Sites: 22

Brief 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.

Conditions

Knee Osteoarthritis; Synovitis of Knee

Keywords

OA; Knee OA; Liraglutide; Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Baseline and Week 4

Secondary Outcomes (15)

• 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

  Baseline, Week 2, Week 6, Week 8, Week 10 and Week 12

• 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

  Baseline, Week 2, Week 4, Week 8 and Week 12

• 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

  Baseline, Week 2, Week 4, Week 8 and Week 12

• Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the Patient Global Assessment of Osteoarthritis (PGA-OA)

  Baseline, Week 2, Week 4, Week 8 and Week 12

• Percentage (%) of OMERACT-OARSI Responders at Week 2, Week 4, Week 8 and Week 12

  Week 2, Week 4, Week 8 and Week 12

Study Arms (2)

4P004 (2mL)

EXPERIMENTAL

One IA injection in the knee of 4P004 (2mL) on the day of randomization

Drug: 4P004

Placebo (NaCl 0.9% 2mL)

PLACEBO COMPARATOR

One IA injection in the knee of Placebo (NaCl 0.9% 2mL) on the day of randomization

Drug: Placebo (NaCl 0.9%)

Interventions

4P004 DRUG

Single intra-articular injection in the knee joint

Also known as: Liraglutide

4P004 (2mL)

Placebo (NaCl 0.9%) DRUG

Single intra-articular injection in the knee joint

Placebo (NaCl 0.9% 2mL)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• 4Moving Biotech: lead

Study Sites (22)

Tucson Orthopaedic Institute

Tucson, Arizona, 85712-2805, United States

RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

Skylight Health Research Burlington

Burlington, Massachusetts, 01803, United States

RECRUITING

Durham Bone and Joint Specialists

Ajax, Canada

RECRUITING

SJHC London Rheumatology Centre

London, Canada

RECRUITING

G.R.M.O. (Groupe de recherche en maladies osseuses) Inc

Québec, Canada

NOT YET RECRUITING

Parker Institute Bispebjerg, Frederiksberg Hospital

Frederiksberg, Denmark

RECRUITING

Sanos Clinic Herlev

Herlev, Denmark

RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

ChU de Nice

Nice, France

RECRUITING

Hôpital Cochin

Paris, France

RECRUITING

Hôpital Lariboisière

Paris, France

RECRUITING

Centre Hospitalier Universitaire CHU de Reims - Hopital Maison Blanche

Reims, France

RECRUITING

Care Access Kraków

Krakow, Poland

RECRUITING

Centrum Medyczne Reuma Park

Warsaw, Poland

RECRUITING

MICS Centrum Medyczne Warszawa

Warsaw, Poland

NOT YET RECRUITING

Clínica Gaias Santiago

A Coruña, 15702, Spain

RECRUITING

Complejo Hospitalario Universitario de A Coruna - Hospital Universitario de A Coruna

A Coruña, Spain

RECRUITING

HLA Clínica Vistahermosa

Alicante, Spain

RECRUITING

Corporacio Sanitaria Parc Tauli - Hospital de Sabadell

Sabadell, Spain

NOT YET RECRUITING

Clinica Nuestra Senora de la Esperanza

Santiago de Compostela, Spain

RECRUITING

Hospital Quirónsalud Sagrado Corazón

Seville, Spain

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Liraglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Francis Berenbaum, MD, PhD

  4

  STUDY CHAIR

Central Study Contacts

Francis Berenbaum, MD, PhD

CONTACT

+330144974059; francis@4movingbiotech.com

Odile Fleurot, MD

CONTACT

odile.fleurot@4p-pharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A total of one hundred and twenty-nine (129) participants will be randomized in the trial, and enrolled in two arms. Participants in the active arm will receive one intra-articular (IA) injection of 4P004 (2mL), while the placebo arm will receive 2mL of NaCl 0.9%. Randomization ratio will be 2:1 (4P004:Placebo).

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: November 10, 2025
• Study Start: June 17, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

ES (6); DK (2); PL (3); US (3); CA (3); FR (5)