Study of APH-1105 in Patients With Mild to Moderate Alzheimer's Disease
- Conditions
- Alzheimer Disease 1DementiaAlzheimer Disease 2Alzheimer Disease 3
- Interventions
- Other: Placebo
- Registration Number
- NCT03806478
- Lead Sponsor
- Aphios
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.5 µg APH-1105 Intranasal (IN) nanoparticles - 0.5 micrograms. The study is planned to include 1 dose of APH 1105 / 0.5 µg, administered twice a week for 12 weeks, for a total of 24 doses. 1.0 µg APH-1105 Intranasal (IN) nanoparticles - 1.0 micrograms. The study is planned to include 1 dose of APH 1105 / 1.0 µg, administered twice a week for 12 weeks, for a total of 24 doses. 2.0 µg APH-1105 Intranasal (IN) nanoparticles - 2.0 micrograms. The study is planned to include 1 dose of APH 1105 / 2.0 µg, administered twice a week for 12 weeks, for a total of 24 doses. Placebo Placebo Intranasal (IN) Placebo nanoparticles. The study is planned to include 1 dose of placebo drug administered twice a week for 12 weeks, for a total of 24 doses.
- Primary Outcome Measures
Name Time Method Safety: Incidence of Treatment-emergent Adverse Events Baseline through 30 days post final treatment dose up to day 60 Number of patients experiencing Adverse (AE) and Serious Adverse (SAE) events during treatment and followup.
Efficacy: Cognition Change Baseline - day 60 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.Efficacy: Change in Cognitive Functioning Baseline - day 60 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.
- Secondary Outcome Measures
Name Time Method Tolerability: [Pharmacokinetics] serum elimination half life Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose Characterize pharmacokinetic effects of APH-1105 exposure in patients with Alzheimer's Disease to determine serum elimination half life(1/2).
Change in Behavioral Functioning Baseline, week 4, 8 12 and week 16 post final dose. Change in the Behavioral Pathology in Alzheimer's Disease Rating Scale -Frequency-Weighted (BEHAVE-AD-FW). The Behavioral Pathology in Alzheimer's Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) assesses the possible neurological basis of behavioral and psychological symptoms of dementia, the relationships between behavioral functioning and cognitive functioning. The scale consists of seven (7) behavioral categories (paranoid and delusional ideation, hallucinations, activity disturbances, aggressiveness, diurnal rhythm disturbances, affective disturbances, anxieties, and phobias) and consists of twenty-five (25) symptoms grouped into these categories. Items are score on a 4 point severity - higher the score, higher the impairment.
Tolerability: [Pharmacokinetics] Cmax Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose Characterize pharmacokinetic effects of APH-1105 exposure in patients with Alzheimer's Disease to determine peak plasma concentration (Cmax).
Tolerability: [Pharmacokinetics] Tmax Blood draws at baseline and 15 minutes, 30minutes, 60minutes, 2 hours, 6hours, 12hours, 24hours, 48hours and 72hours post first administered dose Characterize pharmacokinetic effects of APH-1105 exposure in patients with Alzheimer's Disease to determine peak serum concentration(Tmax).
Tolerability: [Pharmacodynamics] protein kinase C activity Blood draws at baseline, 15 minutes, 30minutes, 60minutes, 2hours, 6hours, 12hours, 24hours, 48hours, and 72hours post first administered dose. Assess the Protein Kinase C Activity in patients treated with multiple doses of APH-1105
Change in Behavioral Disturbance Baseline, week 4, 8 12 and week 16 post final dose. Change in the Neuropsychiatric Inventory (NPI) The Neuropsychiatric Inventory (12 item) is a caregiver/informant-based interview that assesses 12 neuro-psychiatric symptoms of the participant over the previous month. Responses are rated both in terms of frequency (1=rarely, less than once per week; 2=sometimes, about once per week; 3=often, several times per week; and 4=very often, once or more per day) and severity (1=mild; 2=moderate; 3=severe) with composite scores ranging from 0-144. The higher the score the greater symptom severity.
Change in Dementia Symptom Severity Baseline, week 4, 8 12 and week 16 post final dose. Change in the Clinical Dementia Rating Scale(CDR_SB) The Clinical Dementia Rating or CDR measure the stage severity of dementia. It is a five-point scale in which "0" connotes no cognitive impairment, and then the remaining four points are for various stages of dementia, mild to severe.
Evaluate the Quality of Life Status Baseline, week 4, 8, 12 and week 16 post final dose Change in the Clinical Global Impression of Improvement (CGI-I) and the Caregiver Clinical Global Impression of Improvement (CGI-I) is a 3-item observer-rated scale that measures illness severity, global improvement or change, and therapeutic response. It is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Each component of the CGI is rated separately; the instrument does not yield a global score.
Risk of Suicide Baseline, week 4, 8, 12 and week 16 post final dose The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. It is comprised of ten categories, with binary responses (yes/no) to indicate a presence or absence of the behavior. The ten categories included in the C-SSRS are as follows: Category 1 - Wish to be Dead; Category 2 - Non-specific Active Suicidal Thoughts; Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Category 5 - Active Suicidal Ideation with Specific Plan and Intent; Category 6 - Preparatory Acts or Behavior; Category 7 - Aborted Attempt; Category 8 - Interrupted Attempt; Category 9 - Actual Attempt (non-fatal); Category 10 - Completed Suicide. A yes/no binary response is also utilized in assessing self-injurious behavior without suicidal intent. The outcome of the C-SSRS is a numerical score obtained from the these categories.