Safety, Tolerability and Pharmacokinetics of Intraarticular 4P004 Single Dose in Patient With KL 2-4 Osteoarthritic Knee (LASARE)

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of 4P004 Versus Placebo Injected in the Target Knee of Patients With Grade 2 to 4 Osteoarthritis on the Kellgren and Lawrence Severity Index

This phase I study is a multicenter, randomized, double-blind, placebo-controlled study to assess the safety and tolerability of single ascending dose of IA 4P-004 in participants,

• Between 18 and 80 years of age,
• with target knee OA stage KL 2-4 A total of 32 participants will be enrolled in 4 cohorts, in each cohort participants will receive either 4P-004 or placebo (6:2).

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: 4P-004; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • UCL-St Luc
  • Gent, Belgium, 9000
    • AZMaria Middelares
  • Louvain, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who have the capacity to give informed consent and who are willing to comply with all study related procedures and assessments (consent via legally authorized representative will not be accepted),
• Ambulatory participants, agreeing a 24-hour hospitalization,
• Participants between 18 and 80 years of age,
• Female participant of childbearing potential (WOCBP), must use contraceptive consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see section 11.4) for at least 5 days following IMP injection, and must have a negative urine pregnancy test done within 24h before randomization,
• Male participants (whose partners are of childbearing potential) must consent to use methods of contraception consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see section 11.4), for at least 90 days following IMP injection,
• Participants with knee osteoarthritis, KL 2-4 of their target knee (defined at screening as the knee with greater pain based on the participant's evaluation and the investigator's clinical judgment),
• X-rays of the target knee within 6 months (if not, to be performed before randomization),
• ECG within normal range,
• WBC (white blood cell count) > 3500/µL,
• Hemoglobin > 12 g/dL,
• Platelets > 100,000/ µL,
• Creatinine clearance (CrCl) > 60 mL/min,
• Glycemia within normal range,
• AST, ALT < 1.5 upper limit of normal (ULN),
• Amylasemia < 1ULN,
• Negative tests for COVID-19 (if required by the standard practice on site), HIV, HbsAg and hepatitis C Ab (Determination of HIV and hepatitis status can be based on participant-reported medical history, available medical records, and the most recently available laboratory results for the participant [tests performed within the previous 12 months]).

Exclusion Criteria:

• Breastfeeding women,
• Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening,
• Any treatment with glucosamine or chondroitin sulfate in the previous 3 months,
• Any glucagon-like peptide 1 analogue hormones,
• Anticoagulant treatment (current or within the last 10 days),
• Treatment of the target knee with any IA injection (steroids, hyaluronic acid derivatives, PRP ….) within 3 months,
• Knee surgery (of the target knee) performed within the previous 12 months or planned within the next 6 months,
• Any partial knee replacement of the target knee,
• Any known active infections or increased predisposition for the development of infections
• Clinical signs and symptoms of active joint crystal disease, or any inflammatory joint disease,
• Diabetes type I or II,
• Congestive Heart Failure stage III or IV of NYHA classification,
• Inflammatory bowel disease,
• Any other chronic condition that has not been well controlled for a minimum of 3 months,
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer) within the last 5 years,
• Any condition, including laboratory findings, that in the opinion of the investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation, (for example, any abnormal reaction to previous IA injection),
• Hypersensitivity to the active substance liraglutide or to any of the excipients: Disodium phosphate dihydrate, Propylene glycol, Phenol,
• Participation in an interventional clinical research trial within 12 weeks prior.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4P-004 w mg; 4P-004 is administered once intraarticularly in the target knee joint Dose = w mg	Drug: 4P-004; single intraarticular administration in the knee joint; Other Names: Liraglutide
Experimental: 4P-004 x mg; 4P-004 is administered once intraarticularly in the target knee joint Dose = x mg	Drug: 4P-004; single intraarticular administration in the knee joint; Other Names: Liraglutide
Experimental: 4P-004 y mg; 4P-004 is administered once intraarticularly in the target knee joint Dose = y mg	Drug: 4P-004; single intraarticular administration in the knee joint; Other Names: Liraglutide
Experimental: 4P-004 z mg; 4P-004 is administered once intraarticularly in the target knee joint Dose = z mg	Drug: 4P-004; single intraarticular administration in the knee joint; Other Names: Liraglutide
Placebo Comparator: Placebo; Placebo is administered once intraarticularly in the target knee joint	Drug: Placebo; single intraarticular administration in the knee joint; Other Names: NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA.	Number of participants with Adverse Events, serious AEs (SAEs), with abnormal Vital signs, abnormal ECG reading and abnormal Laboratory test results	Day 1-Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA	Plasma concentration of liraglutide following a single IA injection at pre-injection (Time [-4hours-0]) and 2hours, 4hours, 8hours, 12hours, 16hours and 24-hours post injection.	Day 1 to Day 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Biomarkers Identification	Serum and urine OA-related biomarkers (exploratory proteomic research of 4P-004 efficacy-related biomarkers) at Day 1 (Time [-4-0]hours, Time 8hours), Day 2 (Time 24hours) and Day 8.	Day 1, Day 2, Day 8

Collaborators and Investigators

• Sponsor: 4Moving Biotech

Publications and helpful links

General Publications

• Meurot C, Martin C, Sudre L, Breton J, Bougault C, Rattenbach R, Bismuth K, Jacques C, Berenbaum F. Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis. Sci Rep. 2022 Jan 28;12(1):1567. doi: 10.1038/s41598-022-05323-7.

Helpful Links

• 4Moving Biotech (sponsor) web site

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 25, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Liraglutide; OA; Knee OA
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 4MB-LAS-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No