Alzheimer DiseasePhase 2NCT05478031
A Phase 2a Study to Investigate REM0046127 in Mild to Moderate Alzheimer's Disease
A Phase 2 study testing REM0046127 High Dose and REM0046127 Low Dose in people with Alzheimer Disease, run by reMYND at 3 sites in 2 countries.
Trial summary
The purpose of this study is to measure effects on CSF biomarkers, EEG and safety with REM0046127 oral suspension compared with placebo in subjects with mild to moderate Alzheimer disease. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- REM0046127 High Dose and REM0046127 Low Dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 7 Jun 2022to 4 Jun 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mild to moderate AD as characterized by the following clinical, cognitive, and functional criteria.
- Biomarker profile reflecting AD, according to The National Institute on Aging- Alzheimer's Association (NIA-AA) Research Framework based on Screening CSF Aβ1-42 and p-tau concentrations
- Clear EEG deficit as assessed by the EEG reader
- MMSE score above 12 (preferably above 16) and a maximum of 24
- A brain imaging study, such as magnetic resonance imaging (MRI) and/or computed tomography (CT) scan having been performed within last 6 months from day of the Screening visit or during the Screening phase of this study consistent with the clinical diagnosis of AD and excluding other potential causes of dementia. If there has been a significant change in clinical status suggestive of stroke or other possible central neurological disease with onset between the time of the last MRI or CT and the Screening evaluation, an MRI scan should be repeated during Screening procedures if considered appropriate by the Investigator
- Age 50 to 85
Show all 12Show fewer
- BMI above 18 and below 35 kg/m2 (preferably below 30 kg/m2)
- If taking concomitant medications, treated with stable doses of drugs essentially required for chronic medical conditions which do not lead to exclusion, during a period of at least 3 months prior to screening, and dose regimen is expected to remain stable during theconduct of the study
- If taking an approved cholinesterase inhibitor or NMDA antagonist for treatment of Alzheimer's disease, treated with a stable dose for at least 6 months prior to the screening visit and the dose is not expected to change during the study as per investigators judgement, or must be off such Alzheimer medication for a period of 8 weeks prior to screening
- Willing and able to give informed consent.
- Have a caregiver who assists the participant every day and has intimate knowledge of the participant's cognitive, functional, and emotional states and of the participant's personal care. The caregiver must be willing to accompany the participant to all study visits and to supervise IMP administration as well as report adverse events. The caregiver must be willing and able to give informed consent for their own participation and be able to read and write.
- Be able to read, write, speak clearly for the cognitive tests, with eyesight and hearingsufficient to enable completion of the cognitive tests
Who cannot join
- COVID-19 positive test at the screening visit
- Clinical, laboratory or neuro-imaging findings consistent with:
- Other primary degenerative dementia, (dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.) ii. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.) iii. Cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter) iv. Other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.) v. Seizure disorder vi. Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.)
- Current presence of a clinically significant major psychiatric disorder according to the criteria of the DSM-IV, or symptom that could affect the subject's ability to complete the study
- Current clinically significant systemic illness, e.g., neoplasia, that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study
- History of adrenal gland insufficiency
Show all 13Show fewer
- History of severe post-lumbar puncture syndrome
- Abnormalities in the blood clotting system or abnormal coagulation status
- Women of childbearing potential.
- Male subjects with female partners of child-bearing potential who are unwilling or unable to adhere to contraception requirements
- Participation in another clinical study during the last 3 months
- Wheelchair-bound or bed-ridden
- Any other criteria which in the opinion of the Investigator causes the subject not to qualify for the study
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Spain2 sites
Fundacion ACE
Barcelona, 08029
FISEVI Hospital Universitario Virgen del Rocio
Seville, 41013
About this study
Official title: A Randomized, Placebo-controlled, Double-blind, Parallel-group Phase 2a Exploratory Study With Placebo run-in to Investigate PK/PD Effects, Safety, Tolerability and Pharmacokinetics of REM0046127 Oral Suspension Compared With Placebo in Subjects With Mild to Moderate Alzheimer's Disease
The purpose of this study is to measure effects on CSF biomarkers, EEG and safety with REM0046127 oral suspension compared with placebo in subjects with mild to moderate Alzheimer disease.
- The study duration will be up to 2 months for each treated subject
- Each subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period
- Visit frequency: every week
- Number of Subjects: at least 30 subjects with an upper limit of 60 subjects.
- Study Arms and Duration: All subjects will be randomized (1:1:1 allocation) to one ofthree different starting levels after the 14-day run-in period:
- REM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days
- REM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days
- Placebo: placebo oral suspension bid for 28 days
Read the detailed description
REM0046127 is a small molecule intended for the oral treatment of subjects suffering from Alzheimer's disease (AD). The pharmacological mechanism of REM0046127 is based on modulating Orai calcium (Ca2+) channel activity to normalize neuronal Ca2+ homeostasis in ADdiseased neurons. This mechanism is central in the AD-disease cascade and is therefore expected to modulate fast-acting mechanisms like restoration of impaired synaptic function, neuronal network activity (EEG), secretion of tau into CSF and synaptic CSF biomarkers to improve cognition (symptomatic). It is also expected to influence processes with slower kinetics like brain amyloid plaques formation and neuronal cell death to slow or even stop disease progression over time (neuroprotection).
- Conditions
- Alzheimer Disease
- Being tested
- REM0046127 High Dose, REM0046127 Low Dose, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REM0046127 High DoseDrug
Also called 1400mg oral suspension
Each subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period.
REM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days
REM0046127 Low DoseDrug
Also called 350mg oral suspension
Each subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period.
REM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days
PlaceboDrug
Also called 0 mg oral suspension
Each subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period.
Placebo: placebo oral suspension bid for 28 days and during the 14-days run-in phase
| Study group | Role | What they receive |
|---|---|---|
| REM0046127 high dose: 1400mg (700mg bid) oral suspension | Active comparator | REM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days Receives: Drug: REM0046127 High Dose |
| REM0046127 low dose: 350mg (175mg bid) oral suspension | Active comparator | REM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days Receives: Drug: REM0046127 Low Dose |
| Placebo | Placebo comparator | Placebo: placebo oral suspension bid for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Incidence of treatment-emergent adverse events. Number of Adverse Events either related or not related to treatment in the verum arms in comparison to the placebo arm.
Measured: From first dosing to 7 days after last dose as follow-up. 14 days Run-in + 28 days treament + 7 days Follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2022
- Study start7 Jun 2022
- Primary completion4 Jun 2024
- Study completion4 Jun 2024
Why it stopped: Due to the event of repeated elevated transaminase levels in one subject - elevated ALT/AST up to 6x ULN in the absence of any other potential underlying cause - we have decided to terminate the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- reMYND
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jort Vijverberg, MD, Principal investigator, BRC AmsterdamKoen De Witte, PhD, Study director, CEO of reMYND
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05478031
- Sponsor's protocol ID
- REMAD-02
- Status last verified
- Jun 2024
- First submitted
- 9 Jun 2022
- Last updated
- 3 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nuytten M, Voets M, Debroux E, Princen K, Pringels L, Fivaz M, Byl E, Ramael S, De Witte K, Boada M, Morato X, Tartari JP, Lafuente A, Macias EF, Matias-Guiu JA, Vijverberg E, Teunissen CE, Anderer P, Staggs V, Hayman V, Corbett A, Ballard C, Harrison JE, Windisch M, Westman AB, Zetterberg H, Dickson S, Mallinckrodt C, Hendrix S, Cummings J, Griffioen G. Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease. Alzheimers Dement. 2025 Sep;21(9):e70537. doi: 10.1002/alz.70537.
PubMed 40937833
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind, Parallel-group Phase 2a Exploratory Study With Placebo run-in to Investigate PK/PD Effects, Safety, Tolerability and Pharmacokinetics of REM0046127 Oral Suspension Compared With Placebo in Subjects With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05478031
- Acronym / sponsor ID
- REMAD-02
- Conditions
- Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the event of repeated elevated transaminase levels in one subject - elevated ALT/AST up to 6x ULN in the absence of any other potential underlying cause - we have decided to terminate the study.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- reMYNDIndustry (pharma, biotech, devices)
- Study start
- 7 Jun 2022 (actual)
- Primary completion
- 4 Jun 2024 (actual)
- Study completion
- 4 Jun 2024 (actual)
- First posted
- 28 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to measure effects on CSF biomarkers, EEG and safety with REM0046127 oral suspension compared with placebo in subjects with mild to moderate Alzheimer disease.
- The study duration will be up to 2 months for each treated subject
- Each subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period
- Visit frequency: every week
- Number of Subjects: at least 30 subjects with an upper limit of 60 subjects.
- Study Arms and Duration: All subjects will be randomized (1:1:1 allocation) to one ofthree different starting levels after the 14-day run-in period:
- REM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days
- REM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days
- Placebo: placebo oral suspension bid for 28 days
Detailed description
REM0046127 is a small molecule intended for the oral treatment of subjects suffering from Alzheimer's disease (AD). The pharmacological mechanism of REM0046127 is based on modulating Orai calcium (Ca2+) channel activity to normalize neuronal Ca2+ homeostasis in ADdiseased neurons. This mechanism is central in the AD-disease cascade and is therefore expected to modulate fast-acting mechanisms like restoration of impaired synaptic function, neuronal network activity (EEG), secretion of tau into CSF and synaptic CSF biomarkers to improve cognition (symptomatic). It is also expected to influence processes with slower kinetics like brain amyloid plaques formation and neuronal cell death to slow or even stop disease progression over time (neuroprotection).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| REM0046127 high dose: 1400mg (700mg bid) oral suspension | Active comparator | Drug: REM0046127 High DoseREM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days |
| REM0046127 low dose: 350mg (175mg bid) oral suspension | Active comparator | Drug: REM0046127 Low DoseREM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo: placebo oral suspension bid for 28 days |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Mild to moderate AD as characterized by the following clinical, cognitive, and functional criteria.
- A brain imaging study, such as magnetic resonance imaging (MRI) and/or computed tomography (CT) scan having been performed within last 6 months from day of the Screening visit or during the Screening phase of this study consistent with the clinical diagnosis of AD and excluding other potential causes of dementia. If there has been a significant change in clinical status suggestive of stroke or other possible central neurological disease with onset between the time of the last MRI or CT and the Screening evaluation, an MRI scan should be repeated during Screening procedures if considered appropriate by the Investigator
- Age 50 to 85
- BMI above 18 and below 35 kg/m2 (preferably below 30 kg/m2)
- If taking concomitant medications, treated with stable doses of drugs essentially required for chronic medical conditions which do not lead to exclusion, during a period of at least 3 months prior to screening, and dose regimen is expected to remain stable during theconduct of the study
Key exclusion criteria (13 listed)
- COVID-19 positive test at the screening visit
- Clinical, laboratory or neuro-imaging findings consistent with:
- Current presence of a clinically significant major psychiatric disorder according to the criteria of the DSM-IV, or symptom that could affect the subject's ability to complete the study
- Current clinically significant systemic illness, e.g., neoplasia, that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study
- History of adrenal gland insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REM0046127 High DoseAlso: 1400mg oral suspensionEach subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period. REM0046127 high dose: 1400mg (700mg bid) oral suspension per day for 28 days | Drug | REM0046127 high dose: 1400mg (700mg bid) oral suspension |
| REM0046127 Low DoseAlso: 350mg oral suspensionEach subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period. REM0046127 low dose: 350mg (175mg bid) oral suspension per day for 28 days | Drug | REM0046127 low dose: 350mg (175mg bid) oral suspension |
| PlaceboAlso: 0 mg oral suspensionEach subject will start with a 14-day placebo run-in period, followed by a 28-day treatment period and 7-day follow-up period. Placebo: placebo oral suspension bid for 28 days and during the 14-days run-in phase | Drug | Placebo |
Primary outcome
Adverse Events
Time frame: From first dosing to 7 days after last dose as follow-up. 14 days Run-in + 28 days treament + 7 days Follow-up
Incidence of treatment-emergent adverse events. Number of Adverse Events either related or not related to treatment in the verum arms in comparison to the placebo arm.
Results and safety
The study was stopped early (reason given: Due to the event of repeated elevated transaminase levels in one subject - elevated ALT/AST up to 6x ULN in the absence of any other potential underlying cause - we have decided to terminate the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
- Results publication: PubMed 40937833Nuytten M, Voets M, Debroux E, Princen K, Pringels L, Fivaz M, Byl E, Ramael S, De Witte K, Boada M, Morato X, Tartari JP, Lafuente A, Macias EF, Matias-Guiu JA, Vijverberg E, Teunissen CE, Anderer P, Staggs V, Hayman V, Corbett A, Ballard C, Harrison JE, Windisch M, Westman AB, Zetterberg H, Dickson S, Mallinckrodt C, Hendrix S, Cummings J, Griffioen G. Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease. Alzheimers Dement. 2025 Sep;21(9):e70537. doi: 10.1002/alz.70537.
- Individual participant dataSharing planned: No
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jort Vijverberg, MD principal investigator
BRC Amsterdam
Koen De Witte, PhD study director
CEO of reMYND
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REM0046127 High Dose and REM0046127 Low Dose in people with Alzheimer Disease, run by reMYND at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to the event of repeated elevated transaminase levels in one subject - elevated ALT/AST up to 6x ULN in the absence of any other potential underlying cause - we have decided to terminate the study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: From first dosing to 7 days after last dose as follow-up. 14 days Run-in + 28 days treament + 7 days Follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05478031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2025.