An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B

NCT02554773 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: LTE14762ALN-AT3SC-0022015-001395-21U1111-1251-5204
• Study Type: interventional
• Target: 34
• Locations: 5 countries
• Sites: 12

Brief Summary

Primary Objective: To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B Secondary Objectives:

• To investigate the long-term efficacy of fitusiran
• To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX (FIX) or bypassing agents (BPA) and fitusiran for treatment of bleeding episodes
• To assess changes in health-related quality of life (QOL) over time
• To characterize antithrombin (AT) reduction and thrombin generation (TG) increase
• To characterize the pharmacokinetics (PK) of fitusiran

Conditions

Hemophilia A; Hemophilia B

Keywords

Hemophilia; RNAi therapeutic

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations \>3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology

  Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry

  Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m\^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis

  Urine samples collected to determine the significant abnormalities in urine.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs

  Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG)

  Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination

  Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.

  From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

Secondary Outcomes (19)

• Annualized Bleeding Rate (ABR) During the Efficacy Period

  From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Annualized Spontaneous Bleeding Rate During the Efficacy Period

  From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Annualized Joint Bleeding Rate During the Efficacy Period

  From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Time Intervals Between Bleeding Events

  From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

• Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX)

  From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)

Study Arms (1)

Fitusiran

EXPERIMENTAL

Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol.

Drug: Fitusiran (SAR439774)

Interventions

Fitusiran (SAR439774) DRUG

Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)

Fitusiran

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completed and tolerated study drug dosing in study TDR14767 (ALN-AT3SC-001)
• Male aged ≥18 years
• Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level \>5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%
• Willing and able to comply with the study requirements and provide written informed consent

You may not qualify if:

• Clinically significant liver disease
• Patients known to be human immunodeficiency virus seropositive and have a CD4 count \<200 cells/μL
• History of venous thromboembolism
• 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
• Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (12)

Clinical Trial Site

Ann Arbor, Michigan, 48109, United States

Location

Clinical Trial Site

Pittsburgh, Pennsylvania, United States

Location

Clinical Trial Site

Plovdiv, Bulgaria

Location

Clinical Trial Site

Sofia, Bulgaria

Location

Clinical Trial Site

Kirov, Russia

Location

Clinical Trial Site

Moscow, Russia

Location

Clinical Trial Site

Zurich, Switzerland

Location

Clinical Trial Site

Basingstoke, United Kingdom

Location

Clinical Trial Site

Glasgow, United Kingdom

Location

Clinical Trial Site

London, NW3 2QG, United Kingdom

Location

Clinical Trial Site

London, SW17 0QT, United Kingdom

Location

Clinical Trial Site

Truro, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39642315 DERIVED

MeSH Terms

Conditions

Hemophilia A; Hemophilia B

Interventions

fitusiran

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations, MD

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: September 18, 2015
• Study Start: September 18, 2015
• Primary Completion: March 21, 2023
• Study Completion: March 21, 2023
• Last Updated: June 5, 2024
• Results First Posted: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2); CH (1); RU (2); BU (2); GB (5)