Hemophilia A, Hemophilia B
Conditions
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.
Interventions
DRUGALN-AT3SC
Ascending doses of ALN-AT3SC by subcutaneous (sc) injection
DRUGSterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Bulgaria, Russia, Switzerland, United Kingdom, United States
Outcome results
None listed