Long-Term Safety of Simufilam for Alzheimer's Disease

No longer recruiting at 141 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Cassava Sciences, Inc.

Disqualifiers: Neurologic condition, Psychiatric diagnosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 8

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety and tolerability of a drug called simufilam for people with Alzheimer's disease. It includes those who completed specific earlier studies (RETHINK-ALZ or REFOCUS-ALZ). Participants must still show signs of Alzheimer's and have a support person during the study. The trial excludes individuals living in nursing homes with around-the-clock care or those with other serious health conditions. The main goal is to determine the long-term safety of simufilam in these patients. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for Alzheimer's.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

A previous study administered simufilam to individuals with mild-to-moderate Alzheimer's disease for 76 weeks, and most participants tolerated it well. An independent safety board reviewed ongoing safety data and found simufilam safe for continued use. Another study examined its long-term safety over two years and reported no major safety issues. Although simufilam did not show significant improvements in memory and thinking skills in some trials, its safety record remains reassuring for those considering joining a study. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Alzheimer's?

Simufilam is unique because it targets a protein called filamin A, which is thought to play a key role in the progression of Alzheimer's disease. Unlike standard treatments that focus on alleviating symptoms by boosting neurotransmitters, Simufilam aims to restore the normal shape and function of filamin A, potentially addressing an underlying cause of the disease. Researchers are excited about Simufilam because it offers a novel approach that could slow disease progression, rather than just managing symptoms.

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

Research has shown that simufilam, the treatment under study in this trial, may help treat Alzheimer's disease by lowering certain biomarkers linked to the disease. Reducing these biomarkers can suggest a positive effect on the disease's underlying processes. However, the REFOCUS-ALZ trial did not find significant improvements in memory or daily functioning for participants. While simufilam may affect disease markers, its actual benefits on thinking and daily activities remain unclear. More research is needed to understand its effectiveness for Alzheimer's patients. ^{1 4 6 7 8}

Who Is on the Research Team?

James Kupiec, MD

Principal Investigator

Cassava Sciences, Inc.

Are You a Good Fit for This Trial?

This trial is for people who have Alzheimer's Disease and were part of earlier Phase 3 trials called RETHINK-ALZ or REFOCUS-ALZ. Participants need a study partner and must still show symptoms consistent with Alzheimer's. Those in full-time nursing care, with other significant neurological conditions, unstable medical issues, or serious psychiatric diagnoses besides Alzheimer's cannot join.

Inclusion Criteria

Completed RETHINK-ALZ (PTI-125-07) or REFOCUS-ALZ (PTI-125-06)

Availability of a study partner

My condition is still showing signs of Alzheimer's disease.

Exclusion Criteria

Any medical condition that in the opinion of the investigator may affect safety or ability to complete the study

Residence in a skilled nursing facility requiring 24-hour care

I have a brain condition, not Alzheimer's, causing my memory problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline

Baseline assessments conducted using clinical and laboratory assessments from the Week 76 (REFOCUS-ALZ) or Week 52 (RETHINK-ALZ) End-of-Treatment visit

1 day

1 visit (in-person)

Treatment

Participants receive simufilam 100 mg oral tablet, twice daily, with safety assessments every 12 weeks

52 weeks

5 visits (in-person)

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

• Simufilam

Trial Overview The trial is testing the long-term safety and effects of a drug named Simufilam at a dose of 100 mg. It’s an open-label extension, meaning everyone knows they are receiving Simufilam and there’s no placebo group involved.

How Is the Trial Designed?

Group I: Simufilam 100 mg Experimental Treatment 1 Intervention

simufilam 100 mg oral tablet, twice daily

Who Is Running the Clinical Trial?

Cassava Sciences, Inc.

Lead Sponsor

Trials

9

Recruited

3,400+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05026177

Study Details | NCT05026177 | Simufilam 50 mg or 100 ... A 76-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 76 weeks.

2. 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.

3. 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 ...

4. 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 ...

5. 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 ... Topline data from the REFOCUS-ALZ trial showed no significant cognitive or functional benefits with simufilam in patients with mild-to-moderate AD.

6. cassavasciences.com cassavasciences.com/news-releases/news-release-details/cassava-sciences-announces-completion-interim-safety-review-0

Cassava Sciences Announces Completion of an Interim ... An Independent Data and Safety Monitoring Board (DSMB) Recently Evaluated the Interim Patient Safety Database for Oral Simufilam in On-going ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04388254

NCT04388254 | Simufilam (PTI-125), 100 mg, for Mild-to- ... A two-year safety study of simufilam (PTI-125) 100 mg oral tablets twice daily for participants of the previous simufilam studies as wells as additional new ...

8. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.054395

Encouraging interim results at 9 months from an open‐label ... A one-year, open-label, multi-center study is now evaluating simufilam's long-term safety and tolerability and following cognition and ...