A multicentre randomized, double-blind, placebo-controlled, dose-finding, Phase 2 study (MARS-17) of GSK3858279 in adult participants with moderate to severe pain due to knee osteoarthritis.
- Trial ID
- 2022-502799-22-00
- Protocol
- 209978
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicentre, randomized, double-blind, placebo-controlled, dose-finding Phase 2 study is to **characterize the efficacy** of GSK3858279 on pain associated with knee osteoarthritis compared to placebo. This objective is clinically relevant as knee osteoarthritis is a prevalent condition that significantly impacts quality of life, and effective pain management is crucial for improving patient outcomes. The study aims to provide insights into the potential of GSK3858279 as a therapeutic option for individuals suffering from moderate to severe knee osteoarthritis pain.
Participants
The clinical trial involves a total of **340 participants** who are being studied to evaluate the efficacy of GSK3858279 on **knee osteoarthritis pain** compared to a placebo. The study population comprises both male and female subjects, aged between **40 to 80 years**, who have been diagnosed with symptomatic osteoarthritis of the knee for at least six months, as per the American College of Rheumatology criteria. Participants were selected based on specific criteria, including a Kellgren and Lawrence score of 2 or higher on X-ray and a pain score between 4 and 9 on the 11-point Numeric Rating Scale for average daily pain intensity. The trial includes individuals with a **Body Mass Index (BMI)** of less than 40 kg/m². Participants are required to be capable of understanding and participating in all scheduled evaluations and procedures, including the use of a patient eDiary. Both genders are included, with specific contraceptive requirements for women of childbearing potential and their male partners. The trial does not exclude vulnerable populations, ensuring a comprehensive assessment of the intervention's efficacy across a diverse group of individuals.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, placebo-controlled, dose-finding Phase 2 study designed to evaluate the efficacy and safety of GSK3858279 in adult participants with moderate to severe pain due to **knee osteoarthritis**. The trial aims to characterize the efficacy of GSK3858279 on knee osteoarthritis pain compared to placebo. The study will involve the administration of GSK3858279 via **subcutaneous injection** with a maximum daily dose of 400 mg over a treatment period of up to 16 weeks. The trial is expected to commence recruitment on December 18, 2023, and conclude by July 2, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, symptomatic osteoarthritis, and pain scores. The primary endpoint is the change from baseline at Week 12 in the weekly average of average daily pain intensity, assessed on the Numeric Rating Scale (NRS). Follow-up visits will be scheduled to monitor the participants' response to the treatment and ensure adherence to the study protocol. The end-of-study visit will occur after the completion of the treatment period to evaluate the overall outcomes and any adverse effects.
The expected length of participant involvement is approximately 16 weeks, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or any adverse events that may compromise participant safety. Participants must be willing and able to comply with all scheduled evaluations and procedures, including the use of a patient eDiary. The study is not a low-intervention trial and is conducted under the sponsorship of GlaxoSmithKline, with GSK3858279 being the investigational product.
Treatment
The clinical trial involves the administration of **GSK3858279**, an experimental medication developed by GlaxoSmithKline. This investigational product is formulated as an **injection** and is administered via **subcutaneous injection**. The maximum daily dose is 400 mg, with a total maximum dose of 400 mg over the treatment period. The treatment duration is set for a maximum of 16 weeks. The active substance, GSK3858279, is a protein of other origin, and the trial aims to evaluate its efficacy in managing moderate to severe pain associated with knee osteoarthritis.
In addition to the experimental treatment, the study employs a **placebo** control, which consists of **Sterile 0.9% (w/v) Sodium Chloride**. This placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment allocations. The placebo is administered in the same manner as the experimental drug to ensure consistency in the administration process. The use of a placebo is critical in assessing the true efficacy of GSK3858279 by providing a baseline for comparison.
Efficacy
The efficacy of GSK3858279 in the treatment of moderate to severe pain due to knee osteoarthritis will be assessed in a multicentre, randomized, double-blind, placebo-controlled, dose-finding Phase 2 study. The primary endpoint for evaluating efficacy is the change from baseline at Week 12 in the weekly average of average daily pain intensity, which will be assessed using the Numeric Rating Scale (NRS). This scale is a validated tool for measuring pain intensity, where participants rate their pain on an 11-point scale ranging from 0 (no pain) to 10 (worst possible pain).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent 2. Symptomatic OA of the index knee as defined by symptomatic for ≥6 months with a clinical diagnosis of OA as per American College of Rheumatology (ACR) criteria 3. Kellgren and Lawrence (KL) score ≥2 on X-ray in the index knee as obtained during screening [Kellgren, 1957] 4. Pain score ≥4 and ≤9 by the 11-point NRS (0-10) for average daily pain intensity over the past 24 hours in index knee at screening (Visit 1) 5. An average of the average daily pain score of ≥4 and ≤9 by the 11-point NRS (0-10) as an average over the preceding 7 days prior to randomization in the index knee 6. Participant must be willing and able to understand and participate in all scheduled evaluations and to complete all required tests and procedures including the use of patient eDiary. This will be judged by the Investigator during the screening period. 7. BMI <40 kg/m2 8. Male or female • Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: • Not a woman of childbearing potential (WOCBP) OR • Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, during the study intervention period and for at least 16 weeks after the last dose of study intervention • A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention • Male Participants: A male participant with a partner who is a WOCBP is required to use a condom during sexual intercourse throughout the study and for 16 weeks after the last dose of study intervention. 9. Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
- History of significant medical illness which would interfere with the study procedures 2. Recent myocardial infarction or unstable angina, or cerebrovascular event 3. Recent unstable or life-threatening cardiac arrhythmia requiring intervention 4. New York Heart Association Class III and IV Heart failure 5. Prolonged corrected QT interval 6. History or current evidence of any inflammatory arthritis, infective arthritis, Paget's disease, osteonecrosis, osteoporotic fracture or any other joint disease 7. Active flare of gout or pseudogout within last year 8. Recent history of significant trauma or surgery to a knee or hip 9. Radiographic evidence of sub-chondral fractures or abnormalities not consistent with osteoarthritis 10. History of infected joint prosthesis, chronic leg ulcers, permanent in-dwelling catheters, chronic sinusitis, recurrent chest infections or urinary tract infections 11. Any focal or widespread pain syndrome that may interfere with understanding of pain response in index knee 12. Significant pain in any joint other than the index knee or any referred pain that would impact ability to assess pain in index knee 13. Current immunodeficiency diseases 14. Symptomatic herpes zoster within 3 months prior to screening 15. Current or previous active Mycobacterium tuberculosis 16. Evidence of latent tuberculosis 17. History or evidence of any clinically significant psychiatric disorder 18. History or evidence of clinically significant multiple or severe drug allergies 19. Malignancy with protocol defined exceptions 20. Liver • Alanine transferase >1.5x upper limit of normal (ULN) • Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) • Current or chronic history of liver disease or known hepatic or biliary abnormalities 21. estimated creatinine clearance <60 mL/min/1.73m2 23. Planned surgical procedure over the duration of the study 24. Participants with recurrent or chronic infection or with an active infection 25. Live vaccine(s) or live attenuated vaccine(s) within the last 30 days 26. Recent use of intra-articular therapy in either knee 27. Immunomodulators use within protocol defined timeframes 28. Unable or unwilling to discontinue all pain medications 29. Major surgery within 3 months prior to randomization 30.Current enrolment or recent past participation in a clinical study of an investigational medicinal product intervention 31. Exposure to more than 4 investigational medicinal products within 12 months 32. Previous exposure to GSK3858279 33. Participants who are a family member of the site staff 34. Participants who cannot be contacted by phone in an emergency 35. Participants who are unlikely to comply with the protocol 36. Positive human immunodeficiency virus antibody test 38. Positive Hepatitis C antibody test result 39. Positive Hepatitis C RNA test result at screening or within 3 months prior to first IMP dose 40. Active or suspected COVID-19 infection 41. Participants who have had a negative PCR assay initially but have since developed clinical features suggestive of COVID-19 or have had known exposure to COVID-19 42. A positive drug screen test 43. Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding 44. Current drug or a history of drug or alcohol abuse or dependence within a year 45. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study
- Hematological laboratory values at screening: • White blood cell (WBC) count <3.0×109/L • Platelet count <125×109/L • Hemoglobin: Males and females with hemoglobin <11.0 g/dL are excluded. Males with hemoglobin level ≥11.0 g/dL to <13.8 g/dL and females with hemoglobin level ≥11.0 g/dL to <12 g/dL will only be eligible in the absence of signs of acute blood loss and if the hemoglobin level at screening is considered stable
- Evidence of an active hepatitis B infection
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 18 Dec 2023 | 20 |
 Germany | Not Recruiting | 18 Dec 2023 | 20 |
 Spain | Not Recruiting | 18 Dec 2023 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sterile 0.9% (w/v) Sodium Chloride | Placebo | N/A | — | — | — | N/A |