Clinical trial NCT03806478: Study of APH-1105 in Patients With Mild to Moderate Alzheimer's Disease
Official title: Safety, Tolerability and Efficacy Assessment of Intranasal Nanoparticles of APH-1105, A Novel Alpha Secretase Modulator For Mild to Moderate Cognitive Impairment Due to Alzheimer's Disease(AD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Dementia
Alzheimer Disease 1
Alzheimer Disease 2
Alzheimer Disease 3
Keywords: Alzheimer's Disease
Dementia
Lead sponsor: Aphios
Sponsor class: INDUSTRY
First posted: 2019-01-16
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Exploratory Phase 2 Trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety: Incidence of Treatment-emergent Adverse Events
timeFrame: Baseline through 30 days post final treatment dose up to day 60
measure: Efficacy: Cognition Change
timeFrame: Baseline - day 60
measure: Efficacy: Change in Cognitive Functioning
timeFrame: Baseline - day 60
Secondary outcomes:
measure: Tolerability: [Pharmacokinetics] Cmax
timeFrame: Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose
measure: Tolerability: [Pharmacokinetics] Tmax
timeFrame: Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose
measure: Tolerability: [Pharmacokinetics] serum elimination half life
timeFrame: Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose
measure: Tolerability: [Pharmacodynamics] protein kinase C activity
timeFrame: Blood draws at baseline, 15 minutes, 30minutes, 60minutes, 2hours, 6hours, 12hours, 24hours, 48hours, and 72hours post first administered dose.
measure: Change in Behavioral Functioning
timeFrame: Baseline, week 4, 8 12 and week 16 post final dose.
measure: Change in Behavioral Disturbance
timeFrame: Baseline, week 4, 8 12 and week 16 post final dose.
measure: Change in Dementia Symptom Severity
timeFrame: Baseline, week 4, 8 12 and week 16 post final dose.
measure: Evaluate the Quality of Life Status
timeFrame: Baseline, week 4, 8, 12 and week 16 post final dose
measure: Risk of Suicide
timeFrame: Baseline, week 4, 8, 12 and week 16 post final dose
Other outcomes:
Locations:
Study officials:
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