Semaglutide for Alzheimer's Disease

Recruiting at 18 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novo Nordisk A/S

Must be taking: Acetylcholinesterase inhibitors

Must not be taking: Systemic corticosteroids, immunosuppressants

Disqualifiers: Autoimmune diseases, CNS disease, 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: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing if semaglutide, a medicine for diabetes and weight loss, can help people with Alzheimer's disease. The study will last over a year, with participants receiving the medicine through regular injections.

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

The trial requires participants to be on a stable dose of acetylcholinesterase inhibitors for Alzheimer's disease for more than 90 days before starting. If you are taking systemic immunomodulating drugs, you must stop them 12 months before the trial.

Is semaglutide safe for humans?

Semaglutide has been studied for safety in people with type 2 diabetes and those with overweight or obesity. Common side effects include gastrointestinal issues like nausea, but it is generally considered safe for these conditions. ^{1 2 3 4 5}

How is the drug Semaglutide unique for treating Alzheimer's disease?

Semaglutide is unique for Alzheimer's disease as it is primarily known for treating type 2 diabetes and weight management, and its use in Alzheimer's is novel, focusing on its potential effects on brain health and cognitive function. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for men and women aged 55-75 with mild cognitive impairment or mild dementia due to Alzheimer's, confirmed by specific criteria. They must be on a stable dose of Alzheimer's medication for over 90 days and show amyloid presence in the brain. People with significant brain disease, autoimmune diseases, recent vaccinations, or use of immune-modifying drugs can't participate.

Inclusion Criteria

I am between 55 and 75 years old.

Clinical dementia rating (CDR) global score of 0.5 or 1 at screening (visit 1)

Mild cognitive impairment (MCI) or mild dementia of the Alzheimer's type according to the National Institute on Aging-Alzheimer's Association (NIA-AA) 2018 criteria

Exclusion Criteria

I haven't taken any immune system altering drugs in the last year.

I have not received any vaccines within 4 weeks before my first visit or won't until after visit 5.

I have an autoimmune disease like lupus or rheumatoid arthritis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either semaglutide or placebo once-weekly subcutaneous injections for 12 weeks with dose escalation

12 weeks

Weekly visits for injections

Treatment Period 2

All participants receive semaglutide once-weekly subcutaneous injections for 52 weeks with dose escalation for those initially on placebo

52 weeks

Weekly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide

Trial Overview The study tests Semaglutide's effects on the immune system and biological processes in Alzheimer's patients. Initially, participants are randomly given either Semaglutide or a placebo for 12 weeks; afterwards, all receive Semaglutide for 52 weeks. The medicine is administered weekly via an injection pen by a study partner.

How Is the Trial Designed?

Group I: Study intervention period 1 Experimental Treatment 2 Interventions

Participants will receive either semaglutide or placebo matched to semaglutide once-weekly subcutaneous (s.c.) injections for 12 weeks as an add on therapy to standard of care. Participants initially received 0.25 milligram (mg) once weekly and the dose was then escalated once in 4 weeks until the maintenance dose (1.0 mg) was reached: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12).

Group II: Study intervention period 2 Placebo Group 1 Intervention

All participants will receive 1.0 mg semaglutide s.c. injections once weekly for 52 weeks during study intervention period 2 as an add-on therapy to standard of care. Participants randomised to semaglutide s.c. 1.0 mg during study intervention period 1 remained on 1.0 mg target maintenance dose for 52 weeks from weeks 12-64. Participants initially randomised to placebo during study intervention period 1 will receive semaglutide s.c. in dose escalation fashion for 8 weeks (0.25 mg from weeks 12-16 and 0.5 mg from weeks 16-20) followed by a maintenance period from weeks 20-64 at dose 1.0 mg.

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Semaglutide has shown potential protective effects against Alzheimer's disease by enhancing autophagy and inhibiting apoptosis in SH-SY5Y cells treated with Aβ25-35, a model for Alzheimer's.

The study found that semaglutide increased levels of autophagy-related proteins (like LC3II and Beclin-1) and decreased apoptosis-related proteins (like Bax), suggesting a mechanism through which it may help protect against neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. Chang, YF., Zhang, D., Hu, WM., et al.[2021]

In a pooled analysis of phase 3a trials involving patients with type 2 diabetes, semaglutide demonstrated significant reductions in HbA1c and body weight, with greater efficacy observed in patients with higher baseline HbA1c levels.

The safety profile of semaglutide was consistent with other GLP-1 receptor agonists, primarily featuring gastrointestinal side effects, indicating it is a safe option for a wide range of patients with varying diabetes characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials. Aroda, VR., Capehorn, MS., Chaykin, L., et al.[2022]

Oral semaglutide significantly reduces HbA1c levels and body weight in patients with type 2 diabetes, showing greater efficacy than placebo and other antidiabetic agents in a review of 11 randomized controlled trials involving 9890 patients.

While oral semaglutide is effective in managing blood glucose and weight, it is associated with increased gastrointestinal side effects like nausea and vomiting, although it has a favorable safety profile regarding severe hypoglycemia and cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. Avgerinos, I., Michailidis, T., Liakos, A., et al.[2021]

In two phase III trials involving 2764 participants with overweight or obesity, semaglutide 2.4 mg once weekly significantly improved cardiometabolic risk factors, including reductions in waist circumference, blood pressure, and fasting glucose compared to placebo.

The benefits of semaglutide were not sustained after stopping the treatment, indicating that ongoing administration may be necessary to maintain improvements in health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Kosiborod, MN., Bhatta, M., Davies, M., et al.[2023]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

Subcutaneous daratumumab, a monoclonal antibody for multiple myeloma, has been shown to be non-inferior to the traditional intravenous formulation, providing similar efficacy with the added benefits of reduced infusion times and lower rates of infusion-related reactions.

Clinical trials, including PAVO, COLUMBA, and PLEIADES, support the use of subcutaneous daratumumab in both newly diagnosed and relapsed refractory myeloma patients, indicating it may improve patient quality of life and decrease healthcare resource use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma. Paul, B., Atrash, S., Bhutani, M., et al.[2021]

In a phase 3 study involving 307 patients with relapsed and refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved progression-free survival (11.5 months) compared to pomalidomide and dexamethasone alone (6.5 months).

The most common side effects included infusion reactions and upper respiratory infections, with a low incidence of treatment-related deaths, indicating that isatuximab is a relatively safe and effective treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Attal, M., Richardson, PG., Rajkumar, SV., et al.[2020]

Daratumumab significantly improves overall survival (OS) compared to pomalidomide plus low-dose dexamethasone in patients with heavily pretreated multiple myeloma, with hazard ratios indicating a strong treatment benefit (0.56 and 0.51 for two different studies).

The survival advantage of daratumumab is even more pronounced in patients who have not previously been treated with pomalidomide, suggesting it may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. Van Sanden, S., Ito, T., Diels, J., et al.[2019]

The combination of daratumumab, pomalidomide, and low-dose dexamethasone is shown to be a safe and effective treatment for relapsed/refractory multiple myeloma, with significant immune system enhancements observed in patients.

Treatment led to increased activation and proliferation of T cells, particularly CD8+ T cells, while also reducing certain immune cell types, suggesting a mechanism for improved immune-mediated tumor destruction without increasing exhausted T-cell phenotypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. Pierceall, WE., Amatangelo, MD., Bahlis, NJ., et al.[2021]

Citations

1. Scotland pubmed.ncbi.nlm.nih.gov

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Oral semaglutide for type 2 diabetes: A systematic review and meta-analysis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. [2022]

6. England pubmed.ncbi.nlm.nih.gov

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma. [2021]

10. France pubmed.ncbi.nlm.nih.gov

Safety of Subcutaneous Daratumumab in Anti-CD38 Monoclonal Antibody-Naïve Patients with Plasma Cell Disorders: A Multicenter Real-Life Experience. [2023]