A Ph2 dose-finding study (MARS-17) to evaluate the efficacy and safety of GSK3858279 in adults with knee osteoarthritis pain.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

29 Nov 2023 → 3 Dec 2024

Decision date (initial)

2023-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502799-22-00

ClinicalTrials.gov

NCT05838742

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To characterize the efficacy of GSK3858279 on knee OA pain compared to placebo.

Conditions and MedDRA coding

Knee osteoarthritis pain

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. 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 3

1. 1. 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
2. 22. 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
3. 37. Evidence of an active hepatitis B infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline at Week 12 in weekly average of average daily pain intensity, assessed on the Numeric Rating Scale (NRS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 26

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications