RNA (nucleic acid complex) (synonym: ALN-6400) for Hereditary haemorrhagic telangiectasia (HHT)

Inclusion criteria

• {"criterion_text":"- Age and Sex 1. Age ≥18 years, at the time of initial informed consent.\n- 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)\n- 3. Epistaxis severity score (ESS) ≥4 (ie, moderate or severe) measured at screening to assess symptoms and bleeding over the prior 4 weeks.\n- 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.\n- 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.\n- 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

• {"criterion_text":"- 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.\n- 2. Has eGFR of <30 mL/min/1.73m2 at screening (calculation based on the CKD-EPI creatinine equation [2021];.\n- 3. Hemoglobin <6 g/dL at screening."}

Primary endpoints

• {"endpoint_text":"- Frequency of AEs. Safety will also be evaluated through vital signs, ECGs, and clinical laboratory assessments.","definition_or_measurement_approach":"Safety assessed by frequency of adverse events; additionally evaluated through vital signs, ECGs, and clinical laboratory assessments."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in PLG o Plasma activity levels o Plasma protein levels","definition_or_measurement_approach":"Change from baseline in plasminogen (PLG) measures including plasma activity levels and plasma protein levels."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change from baseline in epistaxis measures including intensity-adjusted duration, Epistaxis Severity Score (ESS), duration, frequency, intensity and epistaxis-free days per month (measured by daily patient epistaxis diary and ESS at screening and follow-up)."}
• {"endpoint_text":"- • Change from baseline in hematologic parameters o HSS o Iron infusions o RBC transfusions o Hemoglobin","definition_or_measurement_approach":"Change from baseline in hematologic parameters including Hemorrhage Severity Score (HSS), number of iron infusions, RBC transfusions, and hemoglobin."}
• {"endpoint_text":"- • Change from baseline in QoL/PRO scores o NOSE HHT o mPGI-S","definition_or_measurement_approach":"Change from baseline in quality of life and patient-reported outcomes including NOSE HHT and modified Patient Global Impression of Severity (mPGI-S)."}

Methods

• Study flyers (country/language-specific) — K1_ALN-6400-001_Study-Flyer_DE_English_Public, K1_ALN-6400-001_Study-Flyer_DE_German_Public, K2_ALN-6400-001_Study Flyer_ES_Spanish_Public, K1_ALN-6400-001_Study_Flyer_FR_French_Public — channel: printed/digital flyers; target audience: adult patients with HHT; country-specific materials for Germany (DE), Spain (ES), France (FR).
• Visual talking points (country/language-specific) — K1_ALN-6400-001_Visual-Talking-Points_DE_English_Public, K1_ALN-6400-001_Visual-Talking-Points_DE_German_Public, K2_ALN-6400-001_Visual Talking Points_ES_Spanish_Public, K1_ALN-6400-001_Visual_Talking_Points_FR_French_Public — channel: site/staff talking points for recruitment discussions; target: potential participants; country-specific for DE/ES/FR.
• Recruitment and Informed Consent Procedure documents — K1_ALN-6400-001_Recruitment_and_Informed_Consent_Procedure_DE, K1_ALN-6400-001_Recruitment-Informed-Consent-Procedure_ES_Public, K1_ALN-6400-001_Recruitment_Arrangement_Form_FR_French_Public — channel: site procedures and staff guidance; target: site staff and potential participants; country-specific procedures for Germany, Spain, France.
• Study guides / eCOA patient guides and patient-facing materials — L1_ALN-6400-001_Study-Guide_DE_English_Public, Part B eCOA guides and Patient Guides in DE/ES/FR — channel: participant-facing educational materials and electronic COA support; target: enrolled participants; country-specific language versions.
• Concierge / travel support materials — PFD_Concierge-Travel-Guideline and Concierge Welcome Letters in DE/ES/FR — channel: participant travel/concierge support; target: participants requiring travel assistance; country-specific versions.

Germany

Earliest CTIS Part Ii Submission Date

04-11-2025

Latest Decision Or Authorization Date

27-11-2025

Processing Time Days

23

Number Of Sites

1

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

31-10-2025

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

28

Number Of Sites

1

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

26-11-2025

Processing Time Days

35

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Alnylam Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

codes: 1,12,2,5

Third parties

• {"country":"United States","full_name":"Pace Analytical Life Sciences LLC","duties_or_roles":"QC testing (physicochemical, microbial) - Drug QC testing (physicochemical) - Placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Secondary packaging and labeling - Drug and placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Vetter Pharma-Fertigung GmbH & Co. KG (Langenargen)","duties_or_roles":"QC testing (microbial)- Drug and placebo","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Vetter Pharma-Fertigung GmbH & Co. KG (Ravensburg, Mooswiesen)","duties_or_roles":"QC testing (microbial)- - Drug and placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alnylam U.S. Inc.","duties_or_roles":"QC testing (physicochemical) - Drug","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Alnylam Netherlands B.V.","duties_or_roles":"QP certification of IMP in the EU- Drug and placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Vetter Development Services USA Inc.","duties_or_roles":"Manufacture of drug product - Placebo and Drug","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Vetter Pharma-Fertigung GmbH & Co. KG (Ravensburg, Schuetzenstrasse)","duties_or_roles":"QC testing (microbial) - Drug and placebo","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP (Middleton address)","duties_or_roles":"QC testing (physicochemical; microbial) - Placebo","organisation_type":"Pharmaceutical company"}