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

NCT ID: NCT02035605

Last Updated: 2020-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-20
• Study Completion Date: 2017-07-20

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.

Conditions

Hemophilia A; Hemophilia B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ALN-AT3SC

Group Type: ACTIVE_COMPARATOR

ALN-AT3SC

Intervention Type: DRUG

Ascending doses of ALN-AT3SC by subcutaneous (sc) injection

Sterile Normal Saline (0.9% NaCl)

Group Type: PLACEBO_COMPARATOR

Sterile Normal Saline (0.9% NaCl)

Intervention Type: DRUG

Calculated volume to match active comparator

Interventions

ALN-AT3SC

Ascending doses of ALN-AT3SC by subcutaneous (sc) injection

Intervention Type: DRUG

Sterile Normal Saline (0.9% NaCl)

Calculated volume to match active comparator

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kate Madigan, MD

Role: STUDY_DIRECTOR

Alnylam Pharmaceuticals

Locations

Clinical Trial Site

Pittsburgh, Pennsylvania, United States

Clinical Trial Site

Plovdiv, , Bulgaria

Clinical Trial Site

Sofia, , Bulgaria

Clinical Trial Site

Varna, , Bulgaria

Clinical Trial Site

Kirov, , Russia

Clinical Trial Site

Moscow, , Russia

Clinical Trial Site

Saint Petersburg, , Russia

Clinical Trial Site

Sankt Gallen, , Switzerland

Clinical Trial Site

Zurich, , Switzerland

Clinical Trial Site

Glasgow, , United Kingdom

Clinical Trial Site

London, , United Kingdom

Clinical Trial Site

London, , United Kingdom

Clinical Trial Site

Manchester, , United Kingdom

Clinical Trial Site

Truro, , United Kingdom

Countries

United States; Bulgaria; Russia; Switzerland; United Kingdom

References

Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.

Reference Type: DERIVED

PMID: 39642315 (View on PubMed)

Pasi KJ, Rangarajan S, Georgiev P, Mant T, Creagh MD, Lissitchkov T, Bevan D, Austin S, Hay CR, Hegemann I, Kazmi R, Chowdary P, Gercheva-Kyuchukova L, Mamonov V, Timofeeva M, Soh CH, Garg P, Vaishnaw A, Akinc A, Sorensen B, Ragni MV. Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy. N Engl J Med. 2017 Aug 31;377(9):819-828. doi: 10.1056/NEJMoa1616569. Epub 2017 Jul 10.

Reference Type: DERIVED

PMID: 28691885 (View on PubMed)

Other Identifiers

ALN-AT3SC-001

Identifier Type: -

Identifier Source: org_study_id