A Phase 2 study (NEPTUNE-17) to evaluate efficacy and safety of GSK3858279 in DPNP.

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] - Nervous System Diseases [C10]

Trial duration

14 Dec 2023 → 17 Feb 2025

Decision date (initial)

2023-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502313-28-00

ClinicalTrials.gov

NCT05838755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To characterize the efficacy of GSK3858279 on pain compared to placebo in participants with DPNP.

Conditions and MedDRA coding

Diabetic Peripheral Neuropathic Pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 1. 18-75 years of age inclusive, at the time of signing the informed consent. 2. Type I or Type II diabetes with painful, distal, symmetrical, sensory-motor neuropathy attributed to diabetes, of at least 6 months duration; a. Pain must have begun in bilateral distal lower limbs. b. Pain is not related to underlying infection or trauma. c. Diagnosis confirmed by a positive Douleur Neuropathique 4 [DN4] questionnaire at screening. d. Levels of glycosylated haemoglobin A1c (HbA1c) less than 97 mmol/mol (<11%). 3. On a stable anti-diabetic medication regimen (unchanged dose over the last 30 days for diabetes) prior to screening. Adjustment of insulin dose is acceptable, however, resumption of insulin treatment is not allowed since 30 days prior to screening. 4. No unplanned recent hospitalizations due to noncompliance or uncontrolled diabetes. 5. At screening, a pain score ≥4 and ≤9 by the 11-point NRS (0-10) for average daily pain intensity over the past 24 hours. 6. During the run-in period; An average of the average daily pain score of ≥4 and ≤9 by the 11-point NRS (0-10). Rescue medication use (if required) must be within the permitted allowance.
2. 7. Documented history of insufficient pain relief from, or inability to tolerate, or contraindication to current standard of care therapy, e.g. antidepressants (tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]) OR antiepileptic (anticonvulsant) drugs. 8. 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. 9. BMI within the range of 18 to 40 kg/m2 (inclusive). 10. Male or Female participant; 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%, as described in Section 10.4 during the study intervention period and for at least 16 weeks after the last dose of study intervention. The Investigator should evaluate potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relationship to the first 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. • Additional requirements for pregnancy testing during and after study intervention are located in protocol. • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol

Exclusion criteria 3

1. 1. History of significant medical illness 2. Participant has current painful peripheral neuropathy due to a cause other than diabetes 3. Participant has any lower extremity amputation. 4. Participant has a current or previous foot ulcer within the past 3 months 5. Participants who have complications of diseases that are considered to affect the assessment of diabetic peripheral neuropathic pain. 6. Current immunodeficiency diseases 7. History of recurrent/chronic infections 8. Symptomatic herpes zoster within 3 months prior to screening. 9. Current or previous active Mycobacterium tuberculosis infection regardless of treatment. 10. Evidence of latent tuberculosis (TB) as documented by medical history, examination and TB testing: either a positive (not indeterminate) QuantiFERON TB Gold Plus test or a positive (not indeterminate) T-SPOT test. 11. History of significant allergies to monoclonal antibodies. 12. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder 13. History or evidence of clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions 14. Malignancy • History of malignancy within the last 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. • Breast cancer within the past 10 years.
2. 15. Liver • Alanine Aminotransferase (ALT) >1.5× ULN at screening. • Bilirubin >1.5× ULN at screening (isolated bilirubin >1.5× ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 16. Hematological laboratory values at screening • White blood cell (WBC) count <3.0×109/L • Hemoglobin <10.0 g/dL • Platelet count <125×109/L 17. Myocardial infarction or unstable angina, or cerebrovascular event within 6 months prior to screening. 18. Unstable or life-threatening cardiac arrhythmia requiring intervention within 3 months prior to screening. 19. New York Heart Association (NYHA) Class III or IV heart failure. 20. Corrected QT interval according to Fridericia’s formula (QTcF) >450 msec or QTcF >480 msec in participants with bundle branch block, at screening or Day 1 visit. 21. Estimated creatinine clearance <45 mL/min/1.73 m2 at screening 22. Planned surgical procedure over the duration of the study. 23. Major surgery within 3 months prior to first dose of study intervention. 24. Participants with a recurrent or chronic infection 25. Use of any analgesic medication is prohibited 26. Recent immunomodulator use within pre-specified timeframes 27. Received live or live attenuated vaccine(s) use within pre-specified timeframes 28. Use of pain interventions within 4 weeks of screening.
3. 29. Current enrollment or past participation in a clinical study of an Investigational Medicinal Product within the last 30 days or 5 half-lives (whichever is longer) 30. Exposure to more than 4 new IMPs within 12 months prior, or any previous exposure to GSK3858279. 31. Participants who are a family member of the Investigator or any associate, colleague, and employee assisting in the conduct of the study 32. Participants who cannot be contacted by phone in an emergency. 33. Participants who are unlikely to comply with the protocol 34. Positive human immunodeficiency virus (HIV) antibody test. 35. Has a positive test for active hepatitis B virus. 36. Positive hepatitis C antibody test result. 37. Positive hepatitis C RNA test result 38. Active or suspected COVID-19 infection. 39. A positive drug screen at screening. 40. Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding. 41. Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within a year 42. Sensitivity to any of the study interventions, or components thereof, or drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the weekly average of average daily pain intensity at Week 12, 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 27

Locations

4 EU/EEA countries · 32 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 100 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