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

NCT03806478 | Unknown Phase 2 DMC

• 1 other identifier: APH-1105
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Dementia; Alzheimer Disease 1; Alzheimer Disease 2; Alzheimer Disease 3

Keywords

Alzheimer's Disease; Dementia

Outcome Measures

Primary Outcomes (3)

• Safety: Incidence of Treatment-emergent Adverse Events

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

  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.

  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.

  Baseline - day 60

Secondary Outcomes (9)

• Tolerability: [Pharmacokinetics] Cmax

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

• Tolerability: [Pharmacokinetics] Tmax

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

• 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

• 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.

• Change in Behavioral Functioning

  Baseline, week 4, 8 12 and week 16 post final dose.

Study Arms (4)

0.5 µg

EXPERIMENTAL

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.

Drug: APH-1105

1.0 µg

EXPERIMENTAL

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.

Drug: APH-1105

2.0 µg

EXPERIMENTAL

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.

Drug: APH-1105

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

APH-1105 DRUG

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

0.5 µg; 1.0 µg; 2.0 µg

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aphios: lead

MeSH Terms

Conditions

Dementia; Alzheimer disease type 1; Alzheimer disease type 2; Alzheimer disease, familial, type 3; Alzheimer Disease

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Central Study Contacts

Trevor P Castor, PhD

CONTACT

781 932 6933; tcastor@aphios.com

Judith L Castor, PhD

CONTACT

781 932 6933; jlpcastor@aphios.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Triple Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Exploratory Phase 2 Trial

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 16, 2019
• Study Start: June 1, 2023
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 27, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share