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

Phase 1

Completed

• Conditions: Hemophilia B; Hemophilia A
• Interventions: Drug: Sterile Normal Saline (0.9% NaCl); Drug: ALN-AT3SC

• Registration Number: NCT02035605
• Lead Sponsor: Sanofi

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-13
• Study First Submitted QC: 2014-01-13
• Study First Posted: 2014-01-14
• Study Start: 2014-01-20
• Primary Completion: 2017-07-20
• Study Completion: 2017-07-20
• Status Verified: 2018-06
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2020-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 51

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	-
ALN-AT3SC	ALN-AT3SC	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 Truro, United Kingdom