The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety and Tolerability of ALN-APP in Patients With EOAD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05231785
Recruitment Status : Recruiting
First Posted : February 9, 2022
Last Update Posted : May 3, 2024
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose and multiple doses of ALN-APP administered by intrathecal (IT) injection in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment duration for Part B: 12 months.

Condition or disease Intervention/treatment Phase
Early-Onset Alzheimer Disease Drug: ALN-APP Drug: Placebo Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Single Ascending Dose and Open-label Multi-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ALN-APP in Adult Patients With Early-onset Alzheimer's Disease (EOAD)
Actual Study Start Date : February 4, 2022
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Part A: ALN-APP
Participants will be administered a single dose of ALN-APP.
 Drug: ALN-APP
ALN-APP will be administered intrathecally (IT)
Other Name: mivelsiran
Placebo Comparator: Part A: Placebo
Participants will be administered a single dose of placebo.
 Drug: Placebo
Placebo will be administered IT
Experimental: Part B:
Participants will be administered multiple doses of ALN-APP.
 Drug: ALN-APP
ALN-APP will be administered intrathecally (IT)
Other Name: mivelsiran


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Part A: Frequency of Adverse Events [ Time Frame: Up to 12 months ]
  2. Part B: Frequency of Adverse Events [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :
  1. Part A and Part B: Change from Baseline in Levels of Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein Alpha (sAPPα) and Soluble Amyloid Precursor Protein Beta (sAPPβ) [ Time Frame: Part A up to 12 months; Part B up to 24 months ]
  2. Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites [ Time Frame: Part A up to 12 months; Part B up to 24 months ]
  3. Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites [ Time Frame: Part A up to 12 months; Part B up to 24 months ]
  4. Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe) [ Time Frame: Up to 1 day ]
  5. Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF [ Time Frame: Part A up to 12 months; Part B up to 24 months ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has mild cognitive impairment or mild dementia due to EOAD
  • Has Clinical Dementia Rating (CDR) global score 0.5 or 1.0 and Mini Mental State Examination (MMSE) >20

Exclusion Criteria:

  • Has Non-Alzheimer's disease dementia
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2×upper limit of normal (ULN)
  • Has estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m^2 at Screening
  • Has recently received an investigational agent
  • Has recent treatment with amyloid-targeting antibody

Note: other protocol defined inclusion / exclusion criteria apply

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05231785


Contacts
Layout table for location contacts
Contact: Alnylam Clinical Trial Information Line 1-877-ALNYLAM clinicaltrials@alnylam.com
Contact: Alnylam Clinical Trial Information Line 1-877-256-9526 clinicaltrials@alnylam.com

Locations
Layout table for location information
United States, California
Clinical Trial Site Recruiting
San Diego, California, United States, 92103
United States, Indiana
Clinical Trial Site Recruiting
Indianapolis, Indiana, United States, 46202
Canada, Ontario
Clinical Trial Site Recruiting
Toronto, Ontario, Canada
Canada, Quebec
Clinical Trial Site Recruiting
Montréal, Quebec, Canada
Netherlands
Clinical Trial Site Recruiting
Amsterdam, Netherlands
United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom
Clinical Trial Site Recruiting
Sheffield, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Medical Director Alnylam Pharmaceuticals
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05231785    
Other Study ID Numbers: ALN-APP-001
2023-508363-79-00 ( Other Identifier: EU CT Number )
First Posted: February 9, 2022    Key Record Dates
Last Update Posted: May 3, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alnylam Pharmaceuticals:
EOAD
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders