A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy (cAPPricorn-1)

Alnylam Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Cerebral Amyloid Angiopathy

Treatments: Drug: ALN-APP; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06393712

ALN-APP-002

2023-510137-29-00

Details and patient eligibility

About

The purpose of the study is to evaluate the effect of ALN-APP on measures of CAA disease progression and to characterize the safety, tolerability, and pharmacodynamics (PD) of ALN-APP in adult patients with sporadic CAA (sCAA) and Dutch-type CAA (D-CAA). The study will be conducted over 2 periods: a 24-month double-blind treatment period and an optional 18-month open-label extension (OLE) period. The estimated duration of study participation, inclusive of screening, treatment, and additional safety follow-up, is up to 50 months.

Enrollment: 200 estimated patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (sporadic CAA patients):

• Is 50 years or older
• Has probable CAA per the Boston Criteria Version 2.0

Inclusion Criteria (Dutch-type CAA patients):

• Is 30 years or older
• Has known E693Q amyloid precursor protein (APP) gene mutation for Dutch-type CAA

Exclusion Criteria:

• Moderate or severe stage Alzheimer's disease (AD) or significant cognitive impairment (CI)
• Has a history of previous clinical intracerebral hemorrhage (ICH) with onset less than 90 days prior to anticipated randomization in the study
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×upper limit of normal (ULN) at Screening
• Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 at Screening
• Has recently received an investigational agent
• Has had treatment with amyloid-targeting antibody

Note: other protocol defined inclusion / exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups, including a placebo group

ALN-APP

Experimental group

Description:

Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.

Treatment:

Drug: ALN-APP

Placebo/ALN-APP

Placebo Comparator group

Description:

Participants will be administered multiple doses of placebo during the double-blind treatment period. Participants who continue into the optional open-label extension period will be administered multiple doses of ALN-APP.

Treatment:

Drug: Placebo

Drug: ALN-APP