A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

NCT06659640 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ALN-6400-0012025-522510-23-00
• Study Type: interventional
• Target: 120
• Locations: 6 countries
• Sites: 16

Brief Summary

The purpose of this study is to:

• evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-6400 in healthy volunteers
• evaluate the efficacy, safety, tolerability and PD of multiple doses of ALN-6400 in adult patients with HHT

Conditions

Hereditary Hemorrhagic Telangiectasia

Keywords

siRNA; RNAi therapeutic; Plasminogen; PLG; HHT; Osler-Weber-Rendu; epistaxis

Outcome Measures

Primary Outcomes (2)

• Part A: Frequency of Adverse Events

  Up to Week 36

• Part B: Frequency of Adverse Events

  Up to Week 96

Secondary Outcomes (17)

• Part A: Concentrations of ALN-6400 in Plasma

  Predose and up to 2 days postdose

• Part A: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels

  Predose and up to Week 36 postdose

• Part B: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels

  Screening and up to Week 96 postdose

• Part A: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels

  Predose and up to Week 36 postdose

• Part B: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels

  Part B: Screening and up to Week 96 postdose

Study Arms (4)

Part A: ALN-6400

EXPERIMENTAL

Participants will be administered a single dose of ALN-6400.

Drug: ALN-6400

Part A: Placebo

PLACEBO COMPARATOR

Participants will be administered a single dose of placebo.

Drug: Placebo

Part B: ALN-6400

EXPERIMENTAL

Participants will be administered multiple doses of ALN-6400.

Drug: ALN-6400

Part B: Placebo

PLACEBO COMPARATOR

Participants will be administered multiple doses of placebo.

Drug: Placebo

Interventions

ALN-6400 DRUG

ALN-6400 will be administered subcutaneously (SC)

Part A: ALN-6400; Part B: ALN-6400

Placebo DRUG

Placebo will be administered subcutaneously (SC)

Part A: Placebo; Part B: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A:
• Is a healthy adult volunteer
• Part B:
• Is an adult patient with a clinical diagnosis of HHT

You may not qualify if:

• Part A:
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> upper limit of normal (ULN)
• Has known human immunodeficiency virus (HIV) infection; or known current or chronic hepatitis C virus or hepatitis B virus infection
• Has an estimated glomerular filtration (eGFR) of \<90 mL/min/1.73m\^2 at screening
• Part B:
• Has ALT or AST \>2×ULN
• Has total bilirubin \>1.5×ULN
• Has eGFR of \<30 mL/min/1.73m\^2 at screening
• Parts A and B:
• Is not willing to comply with the contraceptive requirements during the study period

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (16)

Clinical Trial Site

Birmingham, Alabama, 35233, United States

RECRUITING

Clinical Trial Site

Cypress, California, 90630, United States

RECRUITING

Clinical Trial Site

Gainesville, Florida, 32608, United States

RECRUITING

Clinical Trial Site

Indianapolis, Indiana, 46260, United States

NOT YET RECRUITING

Clinical Trial Site

Boston, Massachusetts, 02114, United States

RECRUITING

Clinical Trial Site

Rochester, Minnesota, 55905, United States

RECRUITING

Clinical Trial Site

St Louis, Missouri, 63110, United States

RECRUITING

Clinical Trial Site

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Clinical Trial Site

Camperdown, 2050, Australia

RECRUITING

Clinical Trial Site

Parkville, 3050, Australia

RECRUITING

Clinical Trial Site

Mount Royal, H3P 3P1, Canada

RECRUITING

Clinical Trial Site

Toronto, M5B 1W8, Canada

RECRUITING

Clinical Trial Site

Bordeaux, 33000, France

RECRUITING

Clinical Trial Site

Bron, 69500, France

RECRUITING

Clinical Trial Site

Homburg, 66421, Germany

RECRUITING

Clinical Trial Site

L'Hospitalet de Llobregat, 8907, Spain

RECRUITING

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM; clinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

1-877-256-9526; clinicaltrials@alnylam.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2024
• First Posted: October 26, 2024
• Study Start: November 7, 2024
• Primary Completion (Estimated): January 5, 2028
• Study Completion (Estimated): June 22, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); ES (1); US (8); CA (2); DE (1); FR (2)