Safety, tolerability and pharmacokinetics of intra‑articular 4P‑004 versus sodium chloride placebo in patients with knee osteoarthritis (grade 2‑4)

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What is this study about?

The study focuses on Knee osteoarthritis, a condition in which the cartilage that cushions the ends of the bones in the knee gradually wears away, causing pain and reduced movement. The investigation evaluates a new medication identified as 4P-004, compared with a simple salt solution used as a placebo, both delivered by an intra‑articular injection, meaning the medicine is placed directly into the knee joint. The main purpose is to assess safety, how well the knee tolerates the injection, and the way the drug is processed in the body, known as pharmacokinetics.

Participants will receive a single injection of either the test drug at one of three increasing dose levels (0.3 mg, 1 mg, or 3 mg) or the placebo. After the injection, they will be monitored for a short period, during which vital signs such as blood pressure and heart rhythm are checked, and blood samples are taken to look for any changes in normal lab values. They will also be observed for any uncomfortable feelings in the knee, such as pain, swelling, redness, or tenderness, and any other unwanted effects that might occur during the follow‑up visits.

1 sign informed consent and complete screening

you sign the informed consent form, which explains the study and your rights.

screening assessments are performed, including measurement of vital signs, blood tests, and an electrocardiogram (ecg) from day -7 to day -1.

2 baseline measurements

baseline vital signs, ecg results, and laboratory values are recorded to establish your health status before any injection.

3 randomization to treatment group

you are randomly assigned to receive either the test drug or the placebo.

the assignment is kept confidential and does not affect your care.

4 single intra‑articular injection

a single intra‑articular injection is given into the target knee joint.

if you are in the test‑drug group, the injection contains liraglutide at a dose of 0.3 mg, 1.0 mg, or 3.0 mg (the study uses a 6 mg/ml solution, so the volume is adjusted accordingly).

if you are in the placebo group, the injection contains 2 ml of 0.9 % sodium chloride solution.

5 immediate post‑injection observation

you are observed for a short period after the injection to ensure there are no immediate reactions.

6 pharmacokinetic blood sampling

on day 1, a blood sample is taken before the injection (time 0) to serve as a baseline.

additional blood samples are taken at 2, 4, 8, 12, 16, and 24 hours after the injection to measure the concentration of liraglutide in your blood.

7 daily symptom monitoring

from day 1 through day 29, you record any knee pain, tenderness, swelling, redness, or other symptoms.

you also note any other adverse events that may occur.

8 vital signs checks

your vital signs (blood pressure, heart rate, temperature, and respiratory rate) are measured on days 1 to 8.

9 electrocardiogram (ecg) recordings

ecg recordings are performed from day -7 through day 1 to monitor heart rhythm.

10 laboratory tests

blood laboratory tests, including red and white blood cell counts, hemoglobin, platelets, liver enzymes (alt and ast), blood sugar, amylase, and creatinine clearance, are repeated on days 1 to 8.

11 final safety assessment

on day 29, a final assessment is performed to evaluate overall safety, tolerability, and any remaining adverse events.

Who Can Join the Study?

Must be able to give informed consent themselves and willing to follow all study procedures (consent from a legal representative is not accepted).
Blood test must show hemoglobin greater than 12 g/dL (hemoglobin carries oxygen in the blood).
Blood test must show platelets greater than 100,000 per microliter (platelets help the blood clot).
Kidney function test must show creatinine clearance greater than 60 mL/min (a measure of how well the kidneys work).
Blood sugar level (glycemia) must be within the normal range.
Liver enzyme tests (AST and ALT) must be less than 1.5 times the upper limit of normal (these enzymes indicate liver health).
Blood test for amylasemia must be below the upper limit of normal (amylase helps digest carbohydrates).
Screening must be negative for COVID‑19, HIV, hepatitis B surface antigen (HbsAg) and hepatitis C antibodies (tests to rule out these infections).
Must be able to walk on their own (ambulatory) and agree to stay in the hospital for 24 hours.
Age must be between 18 and 80 years.
If you are a female who could become pregnant (childbearing potential), you must use birth control that follows local rules for at least 5 days after the injection and have a negative urine pregnancy test within 24 hours before randomization.
If you are a male whose partner could become pregnant, you must agree to use birth control that follows local rules for at least 90 days after the injection.
Must have knee osteoarthritis with a Kellgren‑Lawrence grade of 2‑4 in the knee that has the most pain (determined by your evaluation and the doctor’s judgment).
Must have an X‑ray of the target knee taken within the past 6 months (or it will be done before randomization).
Heart test (ECG) must be within normal limits.
White blood cell count (WBC) must be greater than 3.5 × 10⁹ per microliter (measures immune cells).

Who Cannot Join the Study?

Breastfeeding women cannot join the study; this means anyone who is currently feeding a baby with breast milk is not eligible.
People who have signs or symptoms of an active joint crystal disease, such as gout, are excluded.
Anyone with diabetes (type I or type II) cannot participate.
Individuals with congestive heart failure at stage III or IV (more severe heart failure) are not allowed.
Those who have an inflammatory bowel disease like Crohn’s disease or ulcerative colitis are excluded.
Any other long‑term (chronic) health condition that has not been well controlled for at least three months makes a person ineligible.
A history of cancer (any organ) within the past five years disqualifies a participant, except for a localized basal cell skin cancer or early‑stage cervical cancer.
If a doctor believes a condition (including abnormal lab results) could be a risk, a reason to avoid the study, or could affect the study results (for example, a bad reaction to a previous joint injection), the person cannot join.
People who are allergic (hypersensitive) to the study drug liraglutide or any of its ingredients (disodium phosphate dihydrate, propylene glycol, phenol) are excluded.
Anyone who took part in another interventional clinical trial within the last 12 weeks cannot be enrolled.
Use of systemic steroids (glucocorticoids) higher than 10 mg of prednisone (or equivalent) per day within four weeks before screening makes a person ineligible.
Taking the supplements glucosamine or chondroitin sulfate in the past three months excludes a participant.
Use of any glucagon‑like peptide‑1 (GLP‑1) analogue hormones (a type of diabetes medication) disqualifies a person.
Current use of blood‑thinning medicines (anticoagulants) or use within the last ten days prevents enrollment.
Having any injection into the study knee (such as steroids, hyaluronic‑acid products, or platelet‑rich plasma) within the past three months excludes a participant.
Undergoing knee surgery on the study knee within the past 12 months or planning surgery within the next six months makes a person ineligible.
Having a partial knee replacement in the study knee is an exclusion criterion.
Any known active infection or a condition that makes a person unusually prone to infections prevents participation.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Katholieke Universiteit te Leuven	Leuven	Belgium

Other Sites

Site Name	City	Country
Az Maria Middelares Gent	Gent	Belgium
Ckhdwflsa Uqqsbatidbgpaa Suzchikbu	Woluwe-Saint-Lambert	Belgium
Mevmeve Cwcqtnk Lmbcb	Sint-Martens-Latem	Belgium

Trial status

Country	Status	Recruitment Start
Belgium	Not recruiting	30.06.2022

Trial locations

Investigated Drugs:

Liraglutide is the experimental medicine being tested in this study. It is a synthetic version of a natural hormone that helps control blood sugar. In this trial, the drug is injected directly into the knee joint of people with osteoarthritis to see if it is safe and well‑tolerated when given at different strengths. Researchers are watching for any side effects and measuring how the drug moves through the body after a single injection.

Victoza is a commercially available pre‑filled pen that also contains liraglutide. In the trial, the same liraglutide from Victoza is used as the test medicine and is injected into the knee joint. The purpose is to evaluate its safety, how patients feel after the injection, and how the drug is processed in the body when given in this new way.

Investigated Diseases:

Osteoarthritis

Knee osteoarthritis – Knee osteoarthritis is a common joint condition in which the cartilage covering the ends of the thighbone and shinbone gradually breaks down. As the cartilage wears away, the bones rub together, leading to pain, swelling, and reduced movement. The disease often starts with occasional stiffness after activity and progresses to more frequent discomfort even at rest. Over time, small bone growths called osteophytes may develop around the joint, further limiting motion. The condition typically worsens slowly, with symptoms increasing in frequency and intensity as the joint structure continues to deteriorate.

Trial ID:

2022-500271-31-00

Protocol code:

4MB-LAS-P

Trial Phase:

Human Pharmacology (Phase I) – Other

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Safety, tolerability and pharmacokinetics of intra‑articular 4P‑004 versus sodium chloride placebo in patients with knee osteoarthritis (grade 2‑4)

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?