Simufilam for Alzheimer's Disease

(REFOCUS-ALZ Trial)

No longer recruiting at 36 trial locations

Overseen By Stephen Thein, 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, Alcohol 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: 14

Duration: 76 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, simufilam, which might aid individuals with mild-to-moderate Alzheimer's disease by enhancing memory and slowing cognitive decline. Participants will receive either a placebo or one of two doses of simufilam for 76 weeks to assess its safety and effectiveness. Individuals diagnosed with Alzheimer's who maintain stable medication routines may qualify for this trial. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

You don't need to stop your current medications, but they must be stable for a certain period before joining the trial. Alzheimer's medications should be stable for at least 12 weeks, and other chronic medications should be stable for at least 4 weeks before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that simufilam has been safe in earlier studies. In one study over two years, participants took 100 mg of simufilam twice daily, and researchers reported no major safety issues. Another study found that simufilam significantly lowered markers of Alzheimer's disease activity without causing safety problems.

Additionally, early results from another study showed improvements in Alzheimer's symptoms after 6 months of using simufilam, suggesting the treatment was well-tolerated.

While these studies indicate a good safety record for simufilam, individual experiences may differ. Always consult a healthcare provider about any concerns before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard Alzheimer's treatments, like donepezil or memantine, which mainly aim to boost neurotransmitters or regulate glutamate, Simufilam works differently by targeting an altered form of a brain protein called filamin A. This novel approach is thought to restore the normal shape and function of this protein, potentially improving both cognitive and behavioral symptoms. Researchers are excited about Simufilam because it offers a new mechanism of action that could address underlying disease processes rather than just managing symptoms. This could lead to more effective and longer-lasting improvements for patients with Alzheimer's disease.

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

Research has shown that simufilam might help lower certain markers of Alzheimer's disease. In earlier studies, simufilam significantly reduced biological indicators linked to Alzheimer's, suggesting potential benefits for brain health. In this trial, participants will receive either simufilam at 50 mg or 100 mg doses, or a placebo. However, some studies found no major improvement in symptoms for patients taking simufilam compared to those taking a placebo. While there are hopeful signs, the evidence remains unclear about its effectiveness in treating Alzheimer's symptoms. More research is needed to determine how well simufilam works for Alzheimer's disease. ^{1 2 3 6 7}

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 people with mild-to-moderate Alzheimer's who've had consistent Alzheimer's medication doses for 3+ months and haven't smoked in 3+ years. Participants need a study partner to attend screenings.

Inclusion Criteria

Are you experiencing the initial signs of memory loss or Alzheimer's disease?

My Alzheimer's medication dose has been stable for over 3 months.

I quit smoking more than 3 years ago.

Exclusion Criteria

I have not smoked for at least 3 years.

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

, and not meeting the study inclusion criteria, was found in 96 of the 377 (25%) individuals screened

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 76 weeks to evaluate safety and efficacy in enhancing cognition and slowing cognitive decline

76 weeks

Clinic visits every 12 weeks, with an additional visit at 4 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 trial tests the safety and effectiveness of Simufilam, at either 50 mg or 100 mg doses, compared to a placebo over a period of 76 weeks. The goal is to see if it improves cognition or slows decline in Alzheimer's patients.

How Is the Trial Designed?

Group I: Simufilam 50 mg Experimental Treatment 1 Intervention

Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks

Group II: Simufilam 100 mg Experimental Treatment 1 Intervention

Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks

Group III: Placebo Placebo Group 1 Intervention

Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 76 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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04388254

NCT04388254 | Simufilam (PTI-125), 100 mg, for Mild-to- ... All participants will receive simufilam 100 mg tablets twice daily for one year, followed by a 6-month randomized, double-blind period where subjects will ...

2. 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 ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05026177

Study Details | NCT05026177 | Simufilam 50 mg or 100 ... The primary objective of this study is to investigate the safety and efficacy of simufilam (PTI-125) in enhancing cognition and slowing cognitive and functional ...

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 ... Overall, results indicated no statistically significant improvement in simufilam-treated patients compared with those on placebo. Despite ...

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

Simufilam (PTI-125) In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. Simufilam (PTI-125). Evidence ...

7. researchgate.net researchgate.net/profile/Lindsay-Burns-3/publication/357472708_Encouraging_interim_results_at_9_months_from_an_open-label_study_of_simufilam_in_patients_with_Alzheimer's_disease/links/6503392e01428926971cec75/Encouraging-interim-results-at-9-months-from-an-open-label-study-of-simufilam-in-patients-with-Alzheimers-disease?origin=scientificContributions

Final Results of a Phase 2b Study of Sumifilam in ... Biomarker levels improved significantly (all p<0.00001) in patients with mild-to-moderate Alzheimer's disease after 6 months of open-label simufilam. Interim ...