A Phase 1/2 Study to Evaluate ALN-6400 in Adult Healthy Volunteers and Adult Patients with HHT

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alnylam Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

15 Dec 2025 → ongoing

Decision date (initial)

2025-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alnylam Pharmaceuticals, Inc.

External identifiers

EU CT number

2025-522510-23-00

ClinicalTrials.gov

NCT06659640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy, Pharmacodynamic, Others, Pharmacokinetic

To evaluate the safety and tolerability of multiple doses of ALN-6400 in adult patients with HHT

Secondary objectives 2

1. To characterize the PD effects of multiple doses of ALN-6400
2. To evaluate the efficacy of ALN-6400

Conditions and MedDRA coding

Hereditary Hemorrhagic Telangiectasia (HHT)

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age and Sex 1. Age ≥18 years, at the time of initial informed consent.
2. Patient and Disease Characteristics 2. Clinical diagnosis of HHT, either per criterion 2a or 2b: a. Definite diagnosis of HHT as per Curaçao criteria[Shovlin 2000], ie, at least 3 of the 4 criteria: • Recurrent and spontaneous epistaxis. • Multiple telangiectasias on the skin of the hands, lips, face, or inside of the nose or mouth. • Arteriovenous malformations (AVMs) or telangiectasias in 1 or more internal organs, including the lungs, brain, liver, intestines, stomach, and spinal cord. • Family history of HHT (ie, first-degree relative [brother, sister, parent, or child] meeting these same criteria for “definite HHT”). b. Genetic confirmation of HHT (with recurrent and spontaneous epistaxis)
3. 3. Epistaxis severity score (ESS) ≥4 (ie, moderate or severe) measured at screening to assess symptoms and bleeding over the prior 4 weeks.
4. 4. Iron deficiency anemia (ie, hemoglobin <12.0 g/dL in women and <13.0 g/dL in men) at screening; and/or treatment with ≥250 mg of intravenous iron and/or ≥1 red blood cell (RBC) transfusion within 24 weeks of screening.
5. 5. Patient agrees not to undergo procedural or surgical management of nasal telangiectasias/epistaxis (except for emergent situations in which it is required) and agrees not to start new therapies for bleeding in HHT during the DB Treatment Period; during the OLE Period, such treatments and therapies are discouraged but not prohibited. Routine nasal packing is not considered procedural management of epistaxis.
6. Informed Consent 6. Patient is able to understand and is willing and able to comply with the study requirements, including completing the daily patient epistaxis diary (including ≥1 week during screening) and to provide written informed consent.

Exclusion criteria 3

1. 1. Has any of the following laboratory parameter assessments at screening: a. ALT or AST >2×ULN. b. Total bilirubin >1.5×ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if the total bilirubin is <2×ULN. c. INR >2.0.
2. 2. Has eGFR of <30 mL/min/1.73m2 at screening (calculation based on the CKD-EPI creatinine equation [2021];.
3. 3. Hemoglobin <6 g/dL at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of AEs. Safety will also be evaluated through vital signs, ECGs, and clinical laboratory assessments.

Secondary endpoints 4

1. Change from baseline in PLG o Plasma activity levels o Plasma protein levels
2. Change from baseline in epistaxis o Intensity-adjusted epistaxis duration o ESS o Epistaxis duration o Epistaxis frequency o Epistaxis intensity o Epistaxis-free days per month
3. • Change from baseline in hematologic parameters o HSS o Iron infusions o RBC transfusions o Hemoglobin
4. • Change from baseline in QoL/PRO scores o NOSE HHT o mPGI-S

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alnylam Pharmaceuticals Inc.

Sponsor organisation

Alnylam Pharmaceuticals Inc.

Address

300 3rd Street

City

Cambridge

Postcode

02142-1103

Country

United States

Scientific contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Clinical Trial Information Line

Public contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Clinical Trial Information Line

Third parties 10

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications