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

Primary Purpose

Early-Onset Alzheimer Disease

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

ALN-APP

Placebo

About this trial

This is an interventional treatment trial for Early-Onset Alzheimer Disease focused on measuring EOAD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Part A: ALN-APP

Part A: Placebo

Part B:

Arm Description

Participants will be administered a single dose of ALN-APP.

Participants will be administered a single dose of placebo.

Participants will be administered multiple doses of ALN-APP.

Outcomes

Primary Outcome Measures

Part A: Frequency of Adverse Events

Part B: Frequency of Adverse Events

Secondary Outcome Measures

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)

Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites

Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites

Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)

Part A and Part B: Concentration at Time 't' (Ct) of ALN-APP and Potential Metabolites

Full Information

NCT ID

NCT05231785

First Posted

January 30, 2022

Last Updated

October 20, 2023

Sponsor

Alnylam Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05231785

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 4, 2022 (Actual)

Primary Completion Date

July 2025 (Anticipated)

Study Completion Date

July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single intrathecal (IT) doses of ALN-APP in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment for Part B: 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Early-Onset Alzheimer Disease

Keywords

EOAD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Maximum treatment duration for Part A: single dose. Maximum treatment for Part B: 12 months.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part A: ALN-APP

Arm Type

Experimental

Arm Description

Participants will be administered a single dose of ALN-APP.

Arm Title

Part A: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be administered a single dose of placebo.

Arm Title

Part B:

Arm Type

Experimental

Arm Description

Participants will be administered multiple doses of ALN-APP.

Intervention Type

Drug

Intervention Name(s)

ALN-APP

Intervention Description

ALN-APP will be administered intrathecally (IT)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered IT

Primary Outcome Measure Information:

Title

Part A: Frequency of Adverse Events

Time Frame

Up to 14 months

Title

Part B: Frequency of Adverse Events

Time Frame

Up to 24 months

Secondary Outcome Measure Information:

Title

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 14 months; Part B up to 24 months

Title

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 14 months; Part B up to 24 months

Title

Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites

Time Frame

Part A up to 14 months; Part B up to 24 months

Title

Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)

Time Frame

Up to 14 months

Title

Part A and Part B: Concentration at Time 't' (Ct) of ALN-APP and Potential Metabolites

Time Frame

Part A up to 14 months; Part B up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alnylam Clinical Trial Information Line

Phone

1-877-ALNYLAM

clinicaltrials@alnylam.com

First Name & Middle Initial & Last Name or Official Title & Degree

Alnylam Clinical Trial Information Line

Phone

1-877-256-9526

clinicaltrials@alnylam.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Alnylam Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Trial Site

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

Kelowna

State/Province

British Columbia

Country

Canada

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

Toronto

State/Province

Ontario

Country

Canada

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

Montréal

State/Province

Quebec

Country

Canada

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

Amsterdam

Country

Netherlands

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

Groningen

Country

Netherlands

Individual Site Status

Recruiting

Facility Name

Clinical Trial Site

City

London

Country

United Kingdom

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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