Can two drugs together stop Alzheimer's plaques from coming back?

NCT ID NCT06996730

What the study statuses mean

This study's is highlighted.

Recruitment status, easiest to join first

Recruiting now This study
This trial is taking on new participants right now.
Not yet recruiting
Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Sep 02, 2026 · Last updated Sep 03, 2026 · Updated 1 time

Summary

This trial tests two experimental drugs, donanemab and RG6289, in people who carry a specific genetic mutation that causes an inherited, early-onset form of Alzheimer's disease. The study first gives donanemab to clear amyloid plaques from the brain, then randomly assigns participants to receive RG6289, donanemab, both, or placebos to see which approach best keeps amyloid levels low. Researchers measure brain amyloid using PET scans and also track memory and daily functioning. The goal is to learn whether combining these drugs can maintain the benefit of plaque clearance over time.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
donanemab (an antibody given by IV infusion) and RG6289 (an oral tablet), tested alone and in combination
What this could lead to
If it works, this could point toward a way to clear harmful brain plaques and keep them from returning in people with a genetic form of early-onset Alzheimer's, potentially slowing or delaying memory decline.
What could go wrong
This is an early-to-mid-stage trial, so the drugs may not work as hoped or may cause side effects. The results may not apply to people with the more common, late-onset form of Alzheimer's.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2/3

Runs two stages together: whether the treatment works, then large-scale confirmation.

Participants

About 240 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jul 2026

Expected to finish

Jun 2030

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

25 to 65 years

Sex

Anyone

Healthy volunteers

Accepted

You do not need to have the condition being studied to take part.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Membership in PSEN1 E280A mutation carrier kindred. * Agrees to conditions of, and is willing to undergo, genetic testing (e.g., APOE, PSEN1 E280A, and other genetic testing allowed by local regulatory requirements). * Males and females aged 25-65 inclusive. * Must meet one of the following criteria: a. Determined to be cognitively normal as defined by an MMSE of ≥24 for participants with less than 9 years of education or MMSE of ≥26 for participants with 9 or more years of education. b. Or determined to have MCI with amnestic presentation as defined by: 1\. Cognitive concern in the judgment of the Investigator, based in part on the: i. CERAD Word List: Recall \<3 for participants with less than 9 years of education. ii. CERAD Word List: Recall \<5 for participants with 9 or more years of education. iii. Preservation of independence in functional activities in the judgment of the Investigator. c. Or determined to have mild AD dementia as defined by: 1. Meets the 2011 National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria for probable AD, and 2. Has a CDR-GS of 0.5 or 1, with the memory box score ≥0.5. Exclusion Criteria: * Significant medical, psychiatric, or other neurological condition or disorder documented by history, physical, neurological, laboratory examinations that would place the participant at undue risk in the Investigator's judgment or impact the interpretation of efficacy. * History of stroke. * History of severe, clinically significant (persistent neurological deficit or structural brain damage) CNS trauma (e.g., cerebral contusion). * Current presence of bipolar disorder or other clinically significant major psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) or symptom (e.g., hallucinations, agitation, paranoia) that could affect the participant's ability to complete evaluations. * History of seizures (excluding febrile seizures of childhood, or other isolated seizure episodes that were not due to epilepsy in the judgment of the Investigator, and required at most time-limited anticonvulsant treatment, and which occurred more than 7 years prior to the screening visit). * Women who are pregnant or intend to become pregnant during the conduct of this study. * Women who are nursing infants or intend to nurse infants during the conduct of this study. * Known (or prior) hypersensitivity to donanemab, RG6289, or any excipients of RG6289. * History of or active inflammatory bowel disease (e.g., Crohn disease or ulcerative colitis). * Medical history of malignancy in the past 5 years, with the following exceptions: 1. If considered to be cured or, 2. If not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the Investigator, is not likely to require treatment in the ensuing 5 years and, 3. For prostate cancer or basal cell carcinoma, no significant progression over the previous 2 years. 4. In-situ cervix carcinoma that has been successfully treated. 5. Fully excised non-melanoma skin cancers or in-situ melanoma. * Any surgery or hospitalization during the 4 weeks prior to screening or pre-planned/scheduled during the study period that, in the opinion of the Investigator, may compromise eligibility to the study. The Medical Monitor is available to the Investigator to advise and answer any questions. * Inability to tolerate MRI procedures or contraindication to MRI, including, but not limited to, presence of pacemakers not compatible with MRI, 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, in the judgment of the Investigator, would pose a potential hazard in combination with MRI * Prior participation in an anti-amyloid therapy trial is allowed if it has been at least 1 year since the last study dose. * Any other investigational treatment, including anti-amyloid small molecules (i.e., BACEi and GSIs, other GSMs) within five half-lives or 16 weeks prior to screening (calculated from the last safety follow-up visit of the previous study), whichever is longer. Note: The participant may be eligible for this study if it can be documented that he/she was randomized to placebo

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

Only the study team decides who joins. These are the ways to reach them.

  1. The places running it

    1 site. The list below names each one and where it is.

  2. The official record

    ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

    Open the record ↗

  3. A doctor treating you

    A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

  • Neurosciences Group of Antioquia, University of Antioquia

    RECRUITING

    Medellín, Antioquia, Colombia

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