Study of APH-1105 in Patients With Mild to Moderate Alzheimer's Disease

Aphios60 enrolled

Overview

This is a Phase 2 study assessing the safety, tolerability and efficacy of intranasal delivery of APH-1105 for the treatment of mild to moderate Alzheimer's in adult.

This study is a multi-center, randomized, triple blind placebo-control with parallel groups. Patients diagnosed with mild to moderate AD will be enrolled and randomly assigned in a blinded fashion to receive study drug APH-1105. Groups will receive either 0.5 µg (15 active, 5 placebo), 1.0 µg (15 active, 5 placebo), or 2.0 µg (15 active, 5 placebo). A full assessment will be made of all relevant tolerability and safety data. Patients will be administered the study drug outside of the clinic setting by a study partner twice a week. The initial dose of APH-1105 will take place in a clinic setting for the purpose of collecting initial Pharmacokinetic data. The total duration for patient participation will be approximately 18 weeks which includes 1 week for screening, 12 weeks of treatment and followup 4 weeks post final dose. Study visits will occur during screening, baseline, weeks 1, 2, 4, 8, 12 and 16 for a total of 7 visits. Week 16 represents the followup visit after the final dose of study medication. Cognitive assessments will be performed at screening, and will repeat at weeks 4, 12 and 16. Behavioral Functioning and Quality of Life measures will be done at weeks 2,4,8,12 and 16. Blood samples will collected though out the study for Pharmacokinetic analyses.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Dementia Alzheimer Disease 1 Alzheimer Disease 2 Alzheimer Disease 3

Interventions

APH-1105DRUG

The investigational drug product, APH-1105 is a sterile, pyrogen-free lyophilized powder intended for intranasal administration.

PlaceboOTHER

The placebo is a sterile, pyrogen free lyophilized powder identical in appearance to the experimental drug

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria * Males and Females ages \> 50 years of age at screening visit * Probable Alzheimer's Disease according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association(NINCDS-ADRDA) and Diagnostic Statistical Manual (DSM) IV-V criteria * Clinical Dementia Rating Scale (CDR) global score \> 1.0 at the time of screening * Mini-Mental Status Examination score of 22-30 at screening visit CT or MRI of brain, within 12 months prior to randomization, compatible with a diagnosis of Probable Alzheimer's Disease * Physical examination, laboratory data and electrocardiogram results from screening visit must be normal or abnormal findings must be judged not to be clinically significant * Ability to walk, at least with an assistive device * Vision and hearing sufficient to comply with testing * Informed consent from patient, or legal guardian (if applicable) and a caregiver * Living outside an institutional facility * Must have at least 1 informant/study partner Exclusion Criteria * Clinically significant and active pulmonary, gastrointestinal, renal, hepatic, endocrine or cardiovascular system diseases * Other neurological disorders, including but not limited to stroke, Parkinson's Disease, seizure disorder, or head injury with loss of consciousness within the past 5 years * DSM-IV Axis I disorder other than Alzheimer's Disease, including amnesic disorders, schizophrenia or schizoaffective disorder, bipolar disorder, current major depressive episode, psychosis, panic, or post-traumatic stress disorder * CT scan or MRI evidence of hydrocephalus, stroke, a space-occupying lesion, cerebral infection, or any other clinically significant central nervous system disease * Dementia complicated by another organic disease * Dementia complicated by the presence of predominant delusions * Patients with a hematological malignancy or solid tumor who are undergoing treatment, who have completed treatment within the past 6 months, or who still have evidence of active disease * Current drug or alcohol dependency including nicotine addiction (smokers) * Subjects receiving immune-suppressants tricyclic antidepressants anticoagulants or chemotherapeutic agents * Hypertension that is poorly controlled or managed * Any medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause to the participant's cognitive impairment or could lead to discontinuation, lack of compliance, interference with study assessments, or safety concerns * Clinically significant, unstable psychiatric illness * Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year * Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities * History of unstable angina, myocardial infarction, chronic heart failure or clinically significant conduction abnormalities within 1 year prior to Screening Visit 1 * Indication of impaired renal or liver function * Clinically significant systemic illness or serious infection within 30 days prior to or during the screening period * Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening Visit 1, or use of AD medications at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 * Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participants at higher risk for adverse events (AEs), or impair the participant's ability to perform cognitive testing or complete study procedures. * Contraindications to study procedures

Outcomes

Primary Outcomes

Safety: Incidence of Treatment-emergent Adverse Events

Number of patients experiencing Adverse (AE) and Serious Adverse (SAE) events during treatment and followup.

Time frame: Baseline through 30 days post final treatment dose up to day 60

Efficacy: Cognition Change

Change in Alzheimer's Disease Assessment Scale-Cog (ADAS-COG) total score from baseline to post final treatment dose. The Alzheimer's Disease Assessment Scale-Cognitive Subscale test(ADAS-Cog) measures language and memory and is comprised of 2 parts targeting cognitive and non-cognitive functioning. It consists of 11 items which include (but not all) word recall, naming of objects, word recognition, comprehension and word finding. The ADAS-COG is scored 0-70. The higher the score the greater the impairment.

Time frame: Baseline - day 60

Efficacy: Change in Cognitive Functioning

Change in the Hopkins Verbal Learning Test-Revised from baseline to day 60 post final treatment dose The Hopkins Verbal Learning Test, a three-trial list of 12 words is a learning and free recall task. The Hopkins Verbal Learning Test measures episodic memory. The test is made up of three trials which requires the patient to free-recall words from the 12 word list involving yes/no responses. The score range is from 0-12. Lower scores (numbers) indicate more impairment.

Time frame: Baseline - day 60

Secondary Outcomes

Tolerability: [Pharmacokinetics] Cmax

Characterize pharmacokinetic effects of APH-1105 exposure in patients with Alzheimer's Disease to determine peak plasma concentration (Cmax).

Time frame: Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose

Tolerability: [Pharmacokinetics] Tmax

Characterize pharmacokinetic effects of APH-1105 exposure in patients with Alzheimer's Disease to determine peak serum concentration(Tmax).

Central Contacts

Trevor P Castor, PhD

CONTACT

781 932 6933 tcastor@aphios.com

Judith L Castor, PhD

CONTACT

781 932 6933 jlpcastor@aphios.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.