ALADDIN Study - Phase III: Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (VP-AD-301)

A Double-Blind Placebo-Controlled Study of VP4896 For the Treatment of Mild-to-Moderate Alzheimer's Disease

The study is designed to investigate the activity of the hormone drug leuprolide acetate in stabilizing cognitive function in mild-to-moderate AD patients.

VP4896 is a gonadotropin releasing hormone (GnRH) agonist that binds to and inactivates GnRH receptors on the pituitary gland. This decreases the amount of luteinizing hormone released by the pituitary. The hypothesis upon which this trial is designed is that luteinizing hormone is the cause of Alzheimer's disease. VP4896 decreases the amount of luteinizing hormone in the body and, therefore, may decrease or halt the progression of Alzheimer's disease.

This is a double-blind, placebo-controlled, study designed to assess the safety and efficacy of VP4896 (a novel formulation of leuprolide acetate) in the treatment of subjects with mild-to-moderate AD. The study duration is 56 weeks. Approximately 555 participants will be recruited from approximately 80 sites in the United States, Canada, and South America.

The study drug will be administered every eight weeks over a 48 week period. Male subjects randomized to active treatment will also receive testosterone replacement gel.

The change from baseline in ADAS-Cog (cognitive test) score at Week 50 and ADCS-CGIC (global cognitive and behavioral measure) at Week 50 will be the primary efficacy endpoints. Safety will be assessed at all visits and by phone at Week 1.

Inclusion Criteria:

• 60 years of age or older
• Diagnosis of probable mild-to-moderate Alzheimer's Disease
• On a stable dose of an acetylcholinesterase inhibitor (including, but not limited to: donepezil, galantamine, rivastigmine, and tacrine) for at least 120 days prior to baseline and will likely remain on the drug throughout the trial; all participants must be on acetylcholinesterase inhibitors
• No other significant or interfering medical conditions

Exclusion Criteria:

• Significant neurological disease affecting the brain or psychiatric disease other than AD, such as current untreated major depression, schizophrenia, epilepsy, Parkinson's disease, Creutzfeldt-Jakob's disease, or clinical episode of stroke
• Laboratory or clinical signs of untreated, clinically significant abnormal thyroid function, in the Investigator's opinion
• Received other investigational drugs within 30 days or 5 half-lives prior to baseline, whichever is longer
• Taking other medications, with the exception of estrogen, known to affect serum gonadotropin (Gn) concentrations, including but not limited to goserelin, danazol, or leuprolide
• Other exclusion criteria exist--eligibility can be assessed by the trial site