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

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

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