Brief Title
A Phase 1 Study of an Investigational Drug, ALN-AT3SC, in Healthy Volunteers and Hemophilia A or B Patients
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)
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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.
Secondary Outcome
The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples.
Condition
Hemophilia A
Intervention
ALN-AT3SC
Study Arms / Comparison Groups
ALN-AT3SC
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
51
Start Date
January 20, 2014
Completion Date
July 20, 2017
Primary Completion Date
July 20, 2017
Eligibility 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
Gender
Male
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Kate Madigan, MD, ,
Location Countries
Bulgaria
Location Countries
Bulgaria
Administrative Informations
NCT ID
NCT02035605
Organization ID
ALN-AT3SC-001
Responsible Party
Sponsor
Study Sponsor
Sanofi
Study Sponsor
Kate Madigan, MD, Study Director, Alnylam Pharmaceuticals
Verification Date
June 2018