Clinical trial NCT02554773: An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
Official title: An Open-label Extension Study of Subcutaneously Administered Fitusiran in Patients With Moderate or Severe Hemophilia A or B Who Have Participated in a Previous Clinical Study With Fitusiran
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hemophilia A
Hemophilia B
Keywords: Hemophilia
RNAi therapeutic
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-09-18
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: It is anticipated that patients in this study will receive treatment with open label fitusiran for approximately 7 years or until fitusiran becomes commercially available, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG)
timeFrame: 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)
measure: Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination
timeFrame: 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:
measure: Annualized Bleeding Rate (ABR) During the Efficacy Period
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Annualized Spontaneous Bleeding Rate During the Efficacy Period
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Annualized Joint Bleeding Rate During the Efficacy Period
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Time Intervals Between Bleeding Events
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX)
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa)
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC)
timeFrame: From Day 29 up to end of the study, maximum of up to 76 months
measure: Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24
timeFrame: Baseline and Month 24
measure: Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24
timeFrame: Baseline and Month 24
measure: Antithrombin Activity Level at the End of Treatment Regimen
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Thrombin Generation at the End of Treatment Regimen
timeFrame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
measure: Maximum Observed Concentration (Cmax) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
measure: Time to Reach the Maximum Concentration (Tmax) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
measure: Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
measure: Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
measure: Terminal Half-Life (t1/2z) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
measure: Apparent Total Body Clearance (CL/F) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
measure: Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran
timeFrame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
measure: Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration
timeFrame: Postdose, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours at Month 24
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: Clinical Trial Site
state: Michigan
city: Pittsburgh
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Plovdiv
country: Bulgaria
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Kirov
country: Russian Federation
facility: Clinical Trial Site
city: Moscow
country: Russian Federation
facility: Clinical Trial Site
city: Zurich
country: Switzerland
facility: Clinical Trial Site
city: Basingstoke
country: United Kingdom
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: Truro
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations, MD
role: STUDY_DIRECTOR
References: