Simufilam for Alzheimer's Disease

(RETHINK-ALZ Trial)

No longer recruiting at 106 trial locations

Overseen By Carl Griffin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Cassava Sciences, Inc.

Must not be taking: Anti-amyloid antibodies

Disqualifiers: Neurologic condition, Psychiatric diagnosis, Substance use, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called simufilam, which might help people with mild-to-moderate Alzheimer's disease by improving memory and slowing the decline in thinking and daily activities. Participants will receive either simufilam or a placebo (a pill with no active medicine) twice daily for 52 weeks. Those diagnosed with Alzheimer's and who have a study partner available might be a good fit for this study. The trial will assess whether simufilam is safe and effective in alleviating Alzheimer's symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for Alzheimer's.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications, but any Alzheimer's medications must be stable for at least 12 weeks, and other chronic medications must be stable for at least 4 weeks before joining the study.

Is there any evidence suggesting that simufilam is likely to be safe for humans?

Research has shown that simufilam is well-tolerated. One study found it generally safe, with participants experiencing similar side effects whether they took simufilam or not. This suggests the treatment is unlikely to cause unexpected or severe side effects. While awareness of any medication's possible side effects remains important, evidence indicates simufilam is generally safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Simufilam for Alzheimer's disease because it offers a different approach compared to current treatments like donepezil and memantine, which primarily focus on managing symptoms. Simufilam works by targeting filamin A, a protein that is thought to disrupt normal cell function in the brain, potentially addressing the disease's root cause rather than just alleviating symptoms. This novel mechanism of action could lead to a more profound impact on disease progression, giving hope for more effective management of Alzheimer's.

What evidence suggests that simufilam might be an effective treatment for Alzheimer's disease?

Studies have shown that simufilam, which participants in this trial may receive, can lower certain biological indicators linked to Alzheimer's disease, such as those related to brain cell damage and inflammation. Research suggests it might reduce these signs of the disease in the brain and blood. However, some trials did not find simufilam to significantly improve symptoms compared to a placebo, another treatment option in this trial. While simufilam shows promise in affecting the disease's biological markers, evidence on improving actual symptoms remains mixed. Further research is needed to understand its overall effectiveness in treating Alzheimer's disease. ^{1 2 3 4 5}

Who Is on the Research Team?

James Kupiec, MD

Principal Investigator

Cassava Sciences

Are You a Good Fit for This Trial?

This trial is for adults with mild-to-moderate Alzheimer's Disease who have been stable on current AD medications for at least 12 weeks, have a certain range of cognitive function scores, and haven't smoked in 3+ years. They need a study partner and can't join if they've had recent seizures or strokes, uncontrolled diabetes or hypertension, severe psychiatric conditions, specific BMI limits, or are taking certain other AD drugs.

Inclusion Criteria

You have mild to moderate dementia, with a score between 0.5 and 2 on a global rating scale.

You may not participate if you have already taken part in a study involving an experimental drug for the same condition.

My Alzheimer's medication dose has been the same for the last 12 weeks.

Exclusion Criteria

You have struggled with alcohol or drug addiction in the past two years.

I have had a seizure in the last year.

My BMI is between 18.5 and 35.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive simufilam or placebo twice daily for 52 weeks

52 weeks

Clinic visits at baseline, 4 weeks, and every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Simufilam

Trial Overview The study tests the safety and effectiveness of Simufilam (100 mg) compared to a placebo over one year. Participants will take the drug twice daily and attend clinic visits every few months to assess changes in cognition and ability to perform daily activities.

How Is the Trial Designed?

Group I: Simufilam 100 mg Experimental Treatment 1 Intervention

Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks

Group II: Placebo Placebo Group 1 Intervention

Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks

Who Is Running the Clinical Trial?

Cassava Sciences, Inc.

Lead Sponsor

Trials

9

Recruited

3,400+

Premier Research

Collaborator

Premier Research Group plc

Collaborator

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Published Research Related to This Trial

Current pharmacological treatments for Alzheimer's disease primarily focus on providing temporary symptomatic relief, with options like acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine available for managing cognitive symptoms and neuropsychiatric issues.

Despite ongoing research into disease-modifying therapies targeting the amyloid pathway, no significant breakthroughs have been achieved yet, highlighting the challenges in developing effective long-term treatments for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. Franke, AG., Lieb, K., Fellgiebel, A.[2009]

Immunotherapy, particularly monoclonal antibodies targeting amyloid-beta (Aβ), shows promise in treating Alzheimer's disease, with recent trials indicating potential for slowing cognitive decline, especially in early-stage patients.

The monoclonal antibody BAN2401, which targets toxic Aβ protofibrils, has entered clinical trials without the safety issues seen in earlier treatments, suggesting a safer and more effective approach to Alzheimer's therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease. Lannfelt, L., Möller, C., Basun, H., et al.[2021]

Citations

1. cassavasciences.com cassavasciences.com/static-files/12519635-9edf-4ac9-93f9-55fbb32d5dc0

Oral Simufilam in Mild-to-moderate Alzheimer's Disease All efficacy data remains blinded; no interim analyses. • Details of the statistical analysis plans (SAPs) for the P3 trials are being negotiated with FDA and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04388254

NCT04388254 | Simufilam (PTI-125), 100 mg, for Mild-to- ... The objectives of this study are to build the safety database for simufilam (PTI-125) and to investigate its effects on biomarkers, cognition and ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32920628/

PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients PTI-125 significantly reduced biomarkers of Alzheimer's disease pathology, neurodegeneration, and neuroinflammation in both cerebrospinal fluid and plasma.

4. neurologylive.com neurologylive.com/view/simufilam-fails-meet-key-end-points-phase-3-ad-trial

Simufilam Fails to Meet Key End Points in Phase 3 ... Overall, results indicated no statistically significant improvement in simufilam-treated patients compared with those on placebo. Despite ...

5. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Simufilam_(PTI-125).pdf

Simufilam (PTI-125) There are 2 randomized double-blind placebo-controlled phase 3 trials that are currently ongoing, testing the safety and efficacy of PTI-125 treatment (50 mg or ...