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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02035605
Recruitment Status : Completed
First Posted : January 14, 2014
Last Update Posted : December 19, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Description
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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.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
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)
Actual Study Start Date : January 20, 2014
Actual Primary Completion Date : July 20, 2017
Actual Study Completion Date : July 20, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  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. [ Time Frame: 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 Outcome Measures :
  1. 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; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112 ]
  2. 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; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112 ]
  3. 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; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes 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 & C (MAD & MD 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

Part D (MD Phase in patients with inhibitors) Inclusion:

  • Same as Parts B/C
  • A Bethesda inhibitor assay > 0.6 BU/mL

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 & C (MAD & MD phase) exclusion:

  • 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

Part D (MD Phase in patients with inhibitors) exclusion:

  • Same as Parts B/C
  • Patients who are known to be HIV positive and have a CD4 count <200 cells/μL
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02035605


Locations
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United States, Pennsylvania
Clinical Trial Site
Pittsburgh, Pennsylvania, United States
Bulgaria
Clinical Trial Site
Plovdiv, Bulgaria
Clinical Trial Site
Sofia, Bulgaria
Clinical Trial Site
Varna, Bulgaria
Russian Federation
Clinical Trial Site
Kirov, Russian Federation
Clinical Trial Site
Moscow, Russian Federation
Clinical Trial Site
St. Petersburg, Russian Federation
Switzerland
Clinical Trial Site
St. Gallen, Switzerland
Clinical Trial Site
Zurich, Switzerland
United Kingdom
Clinical Trial Site
Glasgow, United Kingdom
Clinical Trial Site
London, United Kingdom, NW3 2QG
Clinical Trial Site
London, United Kingdom, SE1 1YR
Clinical Trial Site
Manchester, United Kingdom
Clinical Trial Site
Truro, United Kingdom
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Kate Madigan, MD Alnylam Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02035605    
Other Study ID Numbers: ALN-AT3SC-001
First Posted: January 14, 2014    Key Record Dates
Last Update Posted: December 19, 2020
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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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