GSK4527226 Open-label Extension Study in Patients with Early Alzheimer's Disease.

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

25 Nov 2025 → 29 Apr 2026

Decision date (initial)

2025-10-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GlaxoSmithKline Research and Development Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy

To evaluate the long-term safety and tolerability of GSK4527226 in all participants with early AD in the OLE, overall and by randomized treatment arm in the parent study.

Secondary objectives 1

1. To describe the progression of AD for all participants in the OLE, overall and by randomized treatment arm in the parent study.

Conditions and MedDRA coding

Alzheimer's Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

IPD plan description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Completion of the Treatment Period in the parent study (NCT06079190). Participants may have missed doses during the Treatment Period or may be on a temporary dose suspension but must not have been permanently discontinued early from study intervention or withdrawn from the parent study.
2. Willing and able to give informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF). Where local regulations permit the inclusion of participants deemed not to have the capacity to provide informed consent, a legally authorized representative must provide informed consent on the participant’s behalf, and the participant must provide assent, in accordance with the local and IRB/IEC regulations and guidelines. A participant’s capacity to provide informed consent will be determined by the investigator in accordance with local and IRB/IEC regulations and guidelines.
3. Availability of an adult person (“study partner”) who, in the investigator's opinion, has frequent and sufficient contact with the participant (e.g., at least 8 hours per week of in-person contact), is able to provide accurate information regarding the participant’s cognitive and functional abilities, agrees to provide information at clinic visits (only those visits which require study partner input for efficacy assessments), and signs the study partner ICF. • The study partner must have sufficient cognitive capacity, in the investigator’s opinion, to accurately report on the participant’s behavior and cognitive and functional abilities throughout the study duration. The study partner must be in sufficiently good general health, in the investigator’s opinion, to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures. • Every effort should be made to have the same study partner from the parent study also participate in the OLE study and continue to participate throughout the duration of the OLE study. If the initial study partner can no longer continue in the study, a replacement study partner meeting the same criteria must be available for the participant to continue in the study. • The study partner does not have to live in the same residence as the participant. If the study partner does not reside with the participant, the investigator must be satisfied that the participant can access or contact the study partner readily. If in doubt about whether a participant's care arrangements are suitable for inclusion, the investigator should discuss this with the medical monitor for adjudication.
4. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: • Is a WONCBP as defined in the protocol Appendix 4 (Section 10.4) OR • Is a WOCBP as defined in the protocol Appendix 4 (Section 10.4) and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in the protocol Appendix 4 (Section 10.4) from at least 14 days prior to the first dose of study intervention until at least 12 weeks after the last administered dose of study intervention. • A WOCBP must have a negative, highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. Additional requirements for pregnancy testing during and after study intervention are provided in the SoA (See protocol Section 1.3). • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. • The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). • 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. Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes (e.g., a female participant who is not heterosexually active becomes active), the participant must discuss this with the investigator, who should determine if a female participant must begin a highly effective method of contraception. If reproductive status is questionable, additional evaluation should be considered.
5. Male participants are eligible to participate if they agree to the following during the study: • Refrain from donating sperm. PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent, OR • Must agree to use contraception/barrier if engaging in heterosexual intercourse with a woman of childbearing potential, as follows: • Agree to use a male condom; and • Female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as described in the protocol Appendix 4.

Exclusion criteria 10

1. QTc assessment at Day 1 (local read) that meets the stopping criteria as described in the protocol Section 7.1.2.
2. Participant is taking or will be starting a prohibited medication as described in the protocol Section 6.9.
3. Evidence of any ARIA or cerebral macrohemorrhage that meets the permanent discontinuation criteria as described in the protocol Section 7.1.3.1. Note: Participants with an ARIA event (as reported from the most recent MRI scan) which does not require permanent discontinuation of study intervention by the criteria in the parent study are not excluded from the OLE, but their dosing will follow the guidelines in the protocol.
4. Other newly identified intracranial hemorrhage aneurysm, vascular malformation, infective lesion, space occupying lesion or brain tumor, or other MRI findings contraindicating participation in the study (e.g., subarachnoid hemorrhage).
5. Newly identified infection(s) that may affect the CNS (e.g., HIV, syphilis, neuroborreliosis, or viral or bacterial meningitis/encephalitis).
6. New diagnosis of moderate to severe alcohol and/or substance use disorder (according to the Diagnostic and Statistical Manual of Mental Disorders [DSM], 5th Edition)
7. Change in participant’s ability to tolerate MRI procedures (e.g., due to anxiety or claustrophobia) or participant has a contraindication to MRI (e.g., the presence of pacemakers that are not MRI-compatible, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that would contraindicate an MRI scan) or any other clinical history or examination finding that would pose a potential hazard in combination with MRI. Those who can tolerate MRI with intermittent use of sedative medication as per local practice do not need to be excluded
8. Newly diagnosed cancer, except any of the following: • Surgically excised and not being actively treated with anticancer therapy or radiotherapy and is not likely to require treatment in the ensuing 3 years except for adjuvant hormonal therapy for localized breast cancer. • Localized prostate cancer with no treatment required. • Localized basal cell carcinoma or squamous cell carcinoma of skin that has been excised with clear margins (i.e., melanoma with metastases would be excluded
9. Newly identified severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
10. Newly identified genetic predisposition for clotting disorder or hemorrhagic disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of treatment emergent AEs, including AESIs and SAEs, during the OLE
2. Incidence and severity of ARIAs during the OLE

Secondary endpoints 1

1. Change from OLE baseline1 during the OLE in cognitive assessments: • CDR-SB • ADAS-Cog14 • MMSE • ADCS-ADL-MCI • iADRS • ADCOMS

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

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 19

Locations

8 EU/EEA countries · 39 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

Documents 114 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