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

Phase 1
Recruiting
Conditions
Hereditary Hemorrhagic Telangiectasia
Interventions
Drug: Placebo
Registration Number
NCT06659640
Lead Sponsor
Alnylam Pharmaceuticals
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

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
96
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A: ALN-6400ALN-6400Participants will be administered a single dose of ALN-6400.
Part B: ALN-6400ALN-6400Participants will be administered multiple doses of ALN-6400.
Part A: PlaceboPlaceboParticipants will be administered a single dose of placebo.
Part B: PlaceboPlaceboParticipants will be administered multiple doses of placebo.
Primary Outcome Measures
NameTimeMethod
Part A: Frequency of Adverse EventsUp to Week 36
Part B: Frequency of Adverse EventsUp to Week 96
Secondary Outcome Measures
NameTimeMethod
Part A: Concentrations of ALN-6400 in PlasmaPredose and up to 2 days postdose
Part B: Change from Baseline in Plasminogen (PLG) in Plasma Protein LevelsScreening and up to Week 96 postdose
Part A: Change from Baseline in Plasminogen (PLG) in Plasma Activity LevelsPredose and up to Week 36 postdose
Part B: Change from Baseline in Plasminogen (PLG) in Plasma Activity LevelsPart B: Screening and up to Week 96 postdose
Part B: Change from Baseline in Epistaxis FrequencyBaseline up to Week 96

Epistaxis frequency will be assessed using a daily patient epistaxis diary.

Part B: Change from Baseline in Iron InfusionsBaseline up to Week 96
Part A: Change from Baseline in Plasminogen (PLG) in Plasma Protein LevelsPredose and up to Week 36 postdose
Part B: Change from Baseline in Intensity-adjusted Epistaxis DurationBaseline up to Week 96

Intensity-adjusted epistaxis duration will be assessed using a daily patient epistaxis diary.

Part B: Change from Baseline in Epistaxis Severity Score (ESS) ScaleBaseline up to Week 96

Validated bleeding scale in HHT scored between 0-10, higher scores indicate worse bleeding.

Part B: Change from Baseline in Epistaxis DurationBaseline up to Week 96

Epistaxis duration will be assessed using a daily patient epistaxis diary.

Part B: Change from Baseline in Epistaxis IntensityBaseline up to Week 96

Epistaxis intensity will be assessed using a daily patient epistaxis diary.

Part B: Change from Baseline in Epistaxis-free Days per MonthBaseline up to Week 96

Epistaxis-free days per month will be assessed using a daily patient epistaxis diary.

Part B: Change from Baseline in Hematologic Support Score (HSS)Baseline up to Week 96

The HSS is a quantitative tool designed to longitudinally assess the red blood cells (RBC) and iron supplementation needs of patients with HHT and other chronic bleeding disorders.

Part B: Change from Baseline in Red Blood Cell (RBC) InfusionsBaseline up to Week 96
Part B: Change from Baseline in HemoglobinBaseline up to Week 96
Part B: Change from Baseline in Quality of Life Patient-reported Outcomes (QoL/PRO) assessed by Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT) ScoreBaseline up to Week 84

HHT-specific QoL/PRO will be assessed using the NOSE HHT score. The NOSE HHT is a 29-item patient-reported, clinically validated outcome measure, with total scores ranging continuously from 0 to 4 with higher scores indicating worse scores.

Part B: Change from Baseline in QoL/PRO assessed by Modified Patient Global Impression of Severity (mPGI-S) ScoreBaseline up to Week 84

HHT-specific QoL/PRO will be assessed using the mPGI-S. The patient will respond to a single question, providing their global impression of change in their overall status and epistaxis experience.

Trial Locations

Locations (1)

Clinical Trial Site

🇨🇦

Montreal, Canada

Clinical Trial Site
🇨🇦Montreal, Canada

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