Long-term Safety and Efficacy Evaluation of GSK4527226 in Early Alzheimer's Disease: An Open-Label Extension Study
- Trial ID
- 2025-521107-42-00
- Protocol
- 223646
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the long-term safety and tolerability of GSK4527226 in individuals with early Alzheimer's disease. This assessment is conducted both overall and by the randomized treatment arm from the parent study to monitor the longitudinal profile of the investigational product. The secondary objective includes:
- Description of the progression of the disease for all participants in the open-label extension, analyzed both globally and by the randomized treatment arm of the parent study.
Participants
This study involves 154 participants diagnosed with Alzheimer's disease. The study population includes both male and female individuals within specified age ranges. Participants are selected based on their completion of the treatment period in a parent study. Eligibility requires the presence of a study partner capable of providing accurate assessments of cognitive and functional abilities. For female participants, requirements include specific contraceptive protocols or non-pregnancy status. Male participants must adhere to sperm donation restrictions and specific contraceptive or abstinence requirements.
Plans and Procedures
This Phase 4, multi-center, single-arm, open-label extension study is designed to evaluate the long-term safety and efficacy of GSK4527226 in individuals with early Alzheimer’s disease. The research methodology focuses on assessing the incidence of treatment-emergent adverse events, including serious adverse events and amyloid-related imaging abnormalities. Secondary objectives include measuring changes from baseline in various cognitive assessments. Participants must have completed the treatment period of the parent study without permanent discontinuation of the study intervention. The study requires the presence of a study partner to provide information regarding cognitive and functional abilities. The total duration of the study period is estimated to conclude by November 2028. The protocol includes specific requirements for contraception and pregnancy testing to ensure participant safety.
Treatment
The experimental medication is GSK4527226, which is administered as a solution for infusion. This substance is delivered via intravenous use to participants diagnosed with early Alzheimer’s disease.
Efficacy
The assessment of efficacy in this study involving participants with early Alzheimer’s disease focuses on changes from the open-label extension baseline. The secondary endpoints include evaluations of cognitive assessments via specific instruments. The measures utilized for these assessments are:
- Clinical Dementia Rating Sum of Boxes
- Alzheimer's Disease Assessment Scale-Cognitive Subscale
- Mini-Mental State Examination
- Alzheimer's Disease Cooperative Study-Activities of Daily Living-Mild Cognitive Impairment
- Integrated Alzheimer's Disease Rating Scale
- Alzheimer's Disease Consortium Outcomes Measured Scale
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- 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.
- 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.
- 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
- QTc assessment at Day 1 (local read) that meets the stopping criteria as described in the protocol Section 7.1.2.
- Participant is taking or will be starting a prohibited medication as described in the protocol Section 6.9.
- 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.
- 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).
- Newly identified infection(s) that may affect the CNS (e.g., HIV, syphilis, neuroborreliosis, or viral or bacterial meningitis/encephalitis).
- 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)
- 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
- 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
- Newly identified severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
- Newly identified genetic predisposition for clotting disorder or hemorrhagic disease.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Finland | Not Recruiting | 25 Dec 2025 | 15 |
 France | Not Recruiting | 25 Dec 2025 | 30 |
 Germany | Not Recruiting | 25 Dec 2025 | 6 |
 Italy | Not Recruiting | 25 Dec 2025 | 29 |
 The Netherlands | Not Recruiting | 25 Dec 2025 | — |
 Norway | Not Recruiting | 25 Dec 2025 | 10 |
 Spain | Not Recruiting | 25 Dec 2025 | 30 |
 Sweden | Not Recruiting | 25 Dec 2025 | 17 |
| Netherlands | — | — | 6 |