Simufilam for Alzheimer's Disease

(RETHINK-ALZ Trial)

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

804 Participants Needed

Trial Summary

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.

How is the drug Simufilam different from other Alzheimer's treatments?

Simufilam is unique because it targets the altered form of a protein called filamin A, which is believed to play a role in the development of Alzheimer's disease, potentially offering a new approach compared to existing treatments that mainly focus on symptoms or amyloid-beta pathology. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests simufilam, a pill taken twice daily, on people with mild-to-moderate Alzheimer's disease. The goal is to see if it can improve memory and slow down the worsening of symptoms by helping the brain work better and reducing harmful swelling. The study will last for about a year and involve periodic check-ups to monitor safety and effectiveness.

Research Team

James Kupiec, MD

Principal Investigator

Cassava Sciences

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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 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

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic strategies for Alzheimer's disease in clinical trials. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Usmarapride (SUVN-D4010), a 5-HT4 receptor partial agonist for the potential treatment of Alzheimer's disease: Behavioural, neurochemical and pharmacological profiling. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

[From symptomatic to disease modifying therapy? Recent developments in the pharmacotherapy of Alzheimer's disease]. [2009]