NCT02035605

Brief Summary

The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jan 2014

Typical duration for phase_1

Geographic Reach
5 countries

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 13, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 14, 2014

Completed
6 days until next milestone

Study Start

First participant enrolled

January 20, 2014

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 20, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 20, 2017

Completed
Last Updated

December 19, 2020

Status Verified

June 1, 2018

Enrollment Period

3.5 years

First QC Date

January 13, 2014

Last Update Submit

December 16, 2020

Conditions

Hemophilia AHemophilia B

Outcome Measures

Primary Outcomes (1)

  • The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation.

    Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112

Secondary Outcomes (3)

  • The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples.

    Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112

  • The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma AT levels.

    Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112

  • The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma TG.

    Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112

Study Arms (2)

ALN-AT3SC

ACTIVE COMPARATOR
Drug: ALN-AT3SC

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR
Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

ALN-AT3SCDRUG

Ascending doses of ALN-AT3SC by subcutaneous (sc) injection

ALN-AT3SC
Sterile Normal Saline (0.9% NaCl)DRUG

Calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

Age18 Years - 65 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy adult males aged 18 to 40 years inclusive at Screening.
  • Subjects with adequate complete blood counts and liver function tests.
  • Willing to provide written informed consent and willing to comply with study requirements.
  • Adult male hemophilia patients aged 18 to 65 years inclusive at Screening.
  • Patients with adequate complete blood counts and liver function tests.
  • Patients with moderate or severe, clinically stable hemophilia A or B (Factor VIII or Factor IX ≤5%).
  • Willing to provide written informed consent and willing to comply with study requirements
  • Same as Parts B/C
  • A Bethesda inhibitor assay \> 0.6 BU/mL

You may not qualify if:

  • Subjects with a personal history and/or family history of venous thromboembolism (VTE)
  • Subjects with a known co-existing thrombophilic disorder
  • Subjects with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
  • Subjects with a history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
  • Subjects who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological including osteoarthritis and other inflammatory diseases, dermatological including rash, eczema, dermatitis, or connective tissue diseases or disorders.
  • Patients with a current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity.
  • Patients who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory or other diseases that in the judgment of the investigator precludes their participation in the study.
  • Patients with a known co-existing thrombophilic disorder
  • Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
  • Patients who are known to be HIV positive and have a CD4 count \<400 cells/μL
  • Same as Parts B/C
  • Patients who are known to be HIV positive and have a CD4 count \<200 cells/μL

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Clinical Trial Site

Pittsburgh, Pennsylvania, United States

Location

Clinical Trial Site

Plovdiv, Bulgaria

Location

Clinical Trial Site

Sofia, Bulgaria

Location

Clinical Trial Site

Varna, Bulgaria

Location

Clinical Trial Site

Kirov, Russia

Location

Clinical Trial Site

Moscow, Russia

Location

Clinical Trial Site

Saint Petersburg, Russia

Location

Clinical Trial Site

Sankt Gallen, Switzerland

Location

Clinical Trial Site

Zurich, Switzerland

Location

Clinical Trial Site

Glasgow, United Kingdom

Location

Clinical Trial Site

London, NW3 2QG, United Kingdom

Location

Clinical Trial Site

London, SE1 1YR, United Kingdom

Location

Clinical Trial Site

Manchester, United Kingdom

Location

Clinical Trial Site

Truro, United Kingdom

Location

Related Publications (2)

  • Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.

    PMID: 39642315DERIVED

  • Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, Kazmi R, Chowdary P, Gercheva-Kyuchukova L, Mamonov V, Timofeeva M, Soh CH, Garg P, Vaishnaw A, Akinc A, Sorensen B, Ragni MV. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med. 2017 Aug 31;377(9):819-828. doi: 10.1056/NEJMoa1616569. Epub 2017 Jul 10.

    PMID: 28691885DERIVED

MeSH Terms

Conditions

Hemophilia AHemophilia B

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, X-Linked

Study Officials

  • Kate Madigan, MD

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2014

First Posted

January 14, 2014

Study Start

January 20, 2014

Primary Completion

July 20, 2017

Study Completion

July 20, 2017

Last Updated

December 19, 2020

Record last verified: 2018-06

Locations

BU(3)CH(2)US(1)RU(3)GB(5)