A Phase 1 Study of an Investigational Drug, ALN-AT3SC, in Healthy Volunteers and Hemophilia A or B Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Alnylam Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02035605
First received: January 13, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Hemophilia A
Hemophilia B
Drug: ALN-AT3SC
Drug: Sterile Normal Saline (0.9% NaCl)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase 1 Single-ascending and Multiple-ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia)

Resource links provided by NLM:


Further study details as provided by Alnylam Pharmaceuticals:

Primary Outcome Measures:
  • 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. [ Time Frame: Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples. [ Time Frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70 ] [ Designated as safety issue: No ]
  • The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma AT levels. [ Time Frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70 ] [ Designated as safety issue: No ]
  • The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma TG. [ Time Frame: Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70 ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: January 2014
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ALN-AT3SC Drug: ALN-AT3SC
Ascending doses of ALN-AT3SC by subcutaneous (sc) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part A (SAD phase) inclusion:

  • 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.

Part B (MAD phase) inclusion:

  • 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

Exclusion Criteria:

Part A (SAD phase) exclusion:

  • 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.

Part B (MAD phase) exclusion:

  • Patients with a history of serious mental illness, that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02035605

Contacts
Contact: Alnylam Clinical Trials Hotline Call for Complete Site List 617-575-7400
Contact: Alnylam Clinical Trials Hotline Call for Complete Site List 1-866-330-0326

Locations
United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Study Director: Benny Sorensen, MD PhD Alnylam Pharmaceuticals
  More Information

No publications provided

Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02035605     History of Changes
Other Study ID Numbers: ALN-AT3SC-001
Study First Received: January 13, 2014
Last Updated: January 13, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014