Skip to main content
TTrialFinderData
TrialFinderData is for informational purposes only and does not provide medical advice. Always talk to your doctor.

Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 2INTERVENTIONAL

Repurposing Siponimod for Alzheimer's Disease

SIPO1-AD: A Phase II Clinical Trial for the Assessment of Safety, Tolerability, and Efficacy of Siponimod in Patients With Mild Alzheimer's Disease

Repurposing Siponimod for Alzheimer's Disease (NCT06639282) is a Phase 2 interventional studying Alzheimer Disease and Mild Alzheimer Disease, sponsored by St. Joseph's Hospital and Medical Center, Phoenix. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Alzheimer Disease and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 105 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Alzheimer Disease subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Male or female at least 50 years of age, but less than 85 (84 at time of screening) 2. Females must be of non-childbearing potential or have negative pregnancy test at time of screening. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for \>12 months prior to the planned date of enrollment. 3. Must have a diagnosis of mild Alzheimer's Dementia determined by medical record review. 4. Vision and hearing must be sufficient to comply with study procedures. 5. Be able to take oral medications. 6. Must be able to attend all study visits indicated in the schedule of visits. 7. Must have a collateral informant/study partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to specified clinic visits, supervise administration of all study medication, and be available for telephone visits/interviews. 8. Documented Mini Mental State Exam (MMSE) score between 20-26 at Screening Visit Day 1. 9. CT or MRI scan of the brain within 12 months of Screening Visit Day 1 showing no evidence of significant focal lesions or other pathology which could contribute to dementia. If neither a CT or a MRI scan is available from the past 12 months, a scan fulfilling the requirements must be obtained before randomization. 10. Hachinski ischemic score must be \< 4. 11. Geriatric depression scale must be \< 10. 12. Prior to dosing all randomized study subjects must show proof they have received immunization to varicella (VZV IgG). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Male or female at least 50 years of age, but less than 85 (84 at time of screening) 2. Females must be of non-childbearing potential or have negative pregnancy test at time of screening. Women of non-childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for \>12 months prior to the planned date of enrollment. 3. Must have a diagnosis of mild Alzheimer's Dementia determined by medical record review. 4. Vision and hearing must be sufficient to comply with study procedures. 5. Be able to take oral medications. 6. Must be able to attend all study visits indicated in the schedule of visits. 7. Must have a collateral informant/study partner who has significant direct contact with the patient at least 10 hours per week and who is willing to accompany the patient to specified clinic visits, supervise administration of all study medication, and be available for telephone visits/interviews. 8. Documented Mini Mental State Exam (MMSE) score between 20-26 at Screening Visit Day 1. 9. CT or MRI scan of the brain within 12 months of Screening Visit Day 1 showing no evidence of significant focal lesions or other pathology which could contribute to dementia. If neither a CT or a MRI scan is available from the past 12 months, a scan fulfilling the requirements must be obtained before randomization. 10. Hachinski ischemic score must be \< 4. 11. Geriatric depression scale must be \< 10. 12. Prior to dosing all randomized study subjects must show proof they have received immunization to varicella (VZV IgG). 13. Each patient must be assessed for capacity to consent by the principal or sub-investigators in order to provide informed consent. If the patient is deemed unable to provide informed consent, they must have a legally authorized representative (LAR), and the LAR must review and sign the informed consent form. If the patient does not have a LAR, the patient must appear able to provide informed consent and must review and sign the informed consent form. If the patient is deemed unable to provide informed consent and does not have a LAR, they cannot participate in the study. In addition, the patient's study partner/informant (as defined in the study inclusion criteria) must sign the informed consent form. If the LAR and the patient's study partner/informant are the same individual, he/she should sign under both. 14. No active suicidality identified on Columbia-Suicide Severity Rating Scale (C-SSRS). 15. Patients with stable prostate cancer may be included at the discretion of the Medical Monitor. 16. Patients who are on monoclonal antibody medication for the treatment of Alzheimer's (ex. lecanemab, donanemab) for \> 6 months or have discontinued monoclonal antibody medication for the treatment of Alzheimer's for \> 6 months may be included if all other criteria has been met. Exclusion Criteria: 1. Taking one of the following medications: Medications for treatment of cancer or other drugs that weaken the immune system (ex. Natalizumab and Rituximab), Amiodarone, Bishydroxycoumarin, Chloramphenicol, Cimetidine, Fluconazole, Fluvastatin, Miconazole, Phenylbutazone, Sulphinpyrazone, Sulphadiazine, Sulphamethizole, Sulfamethoxazole, Sulphaphenazole, Trimethoprim, and Zafirlukast. 2. Current active infection in participants including, but not limited to, herpes zoster, herpes infection, bronchitis, sinusitis, upper respiratory infection and fungal skin infection. Siponimod may increase the risk in participants with active infections. 3. If participant received mRNA COVID-19 vaccination, must have received last dose at least 3 months prior to first dose of study drug/placebo. 4. Current evidence or history within the last 3 years of a neurological or psychiatric illness that could contribute to dementia, including (but not limited to) epilepsy, focal brain lesion, Parkinson's disease, seizure disorder, or head injury with loss of consciousness. 5. Meets DSM IV criteria for any major psychiatric disorder including psychosis, major depression and bipolar disorder. 6. Known history of or self-reported active alcohol and/ or substance abuse within the past three years. 7. Isolated living circumstances which would prohibit a study partner from providing sufficient and credible information about the participant. 8. Poorly controlled hypertension 9. Known Atrioventricular heart block, known heart block type I-III. 10. History of myocardial infarction or signs or symptoms of unstable coronary artery disease within the last year (including revascularization procedure/angioplasty). 11. Severe pulmonary disease (including chronic obstructive pulmonary disease) requiring more than 2 hospitalizations within the past year. 12. Untreated obstructive sleep apnea. 13. Any thyroid disease (unless euthyroid on treatment for at least 6 months prior to screening). 14. Active neoplastic disease (except for skin tumors other than melanoma) within five years. 15. Absolute lymphocytopenia of \<1,000/mm3, or a history of lymphocytopenia within the past two years. 16. Absolute neutropenia of \<1,000/mm3, or a history of neutropenia within the past two years. 17. History of/ or current thromboembolism (including deep venous thrombosis). 18. Any clinically significant hepatic or renal disease (including presence of Hepatitis B or C surface antigen or an elevated transaminase levels of greater than 2x the upper limit of normal (ULN) or creatinine greater than 1.5 x upper limit of normal (ULN)). 19. Clinically significant hematologic or coagulation disorder including any unexplained anemia, or a platelet count less than 100,000/µL at screening. 20. Use of any investigational drug within 30 days or within five half-lives of the investigational agent, whichever is longer. 21. Unwilling or unable to undergo CT or MRI imaging. 22. In the opinion of the investigator, participation would not be in the best interest of the subject. 23. Subjects with CYP2C9\*3/\*3 genotyping

Treatments Being Tested

DRUG

Siponimod

Siponimod (formerly known as BAF312 and completed trial NCT #01665144) has been FDA approved since 2019 (IND #076122) for the treatment of multiple sclerosis. Siponimod is an immunomodulator that prevents the egression of T lymphocytes from peripheral lymphoid organs.

DRUG

Placebo

A placebo that resembles siponimod will be given once daily to participants randomly assigned into the placebo arm.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06639282), the sponsor (St. Joseph's Hospital and Medical Center, Phoenix), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06639282 clinical trial studying?

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod i… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06639282?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06639282?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06639282. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06639282. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.