Clinical trial NCT06145373: A Study to Test a Medicine (Fitusiran) for Preventing Bleeds in People With Severe Hemophilia Who Previously Received Preventive Treatment With Emicizumab
Official title: An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥18 Years of Age With Severe Hemophilia A, With or Without Inhibitors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hemophilia A
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-11-24
Enrollment: 20
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: This is an exploratory, single group, Phase 1, 1-arm study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.

This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥18 years, who were previously receiving emicizumab prophylaxis.

Study details include:

* The study duration will be up to approximately 28 months:

  * There will be an approximately 2-month screening period.
  * There will be a transition period before fitusiran treatment starts (pre-fitusiran treatment period)
  * The fitusiran treatment duration will be up to 18-months (fitusiran treatment period)
  * The antithrombin (AT) follow-up (FU) period will be up to 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%).
* The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.


Eligibility criteria: Inclusion Criteria:

* Male participants must be ≥18 years of age inclusive, at the time of signing the informed consent
* Diagnosis of severe congenital hemophilia A (FVIII \< 1%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.

  * Inhibitor titer of ≥0.6 BU/mL at Screening, or
  * Inhibitor titer of \<0.6 BU/mL at Screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, or
  * Inhibitor titer of \<0.6 BU/mL at Screening with medical record evidence of anamnestic response.
* Participants who are currently on the full labeled dose of emicizumab prophylaxis, irrespective of inhibitor/non-inhibitor status.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:

* Known coexisting bleeding disorders
* History of antiphospholipid antibody syndrome.
* History of arterial or venous thromboembolism, atrial fibrillation, significant valvular disease, myocardial infarction, angina, transient ischemic attack, or stroke. Participants who have experienced thrombosis associated with indwelling venous access may be enrolled.
* Presence of clinically significant liver disease
* Current or prior participation in a fitusiran trial
* Current or prior participation in a gene therapy trial
* AT activity \<60% at Screening, as determined by central laboratory measurement
* Coexisting thrombophilic disorder - Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
* Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
* Presence of acute or chronic hepatitis B infection
* Known to be HIV positive with CD4 count \<200 cells/μL.
* Reduced renal function

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Number of participants with Adverse events (AEs) during the fitusiran treatment
timeFrame: From Day 1 up to Month 4
Secondary outcomes:
measure: The peak thrombin generation (TG) - pre fitusiran treatment
timeFrame: From Month -2 up to Day 1
measure: The peak TG during fitusiran treatment
timeFrame: From Day 1 up to Month 4
measure: The peak antithrombin (AT) levels during pre-fitusiran treatment
timeFrame: From Month -2 up to Day 1
measure: The peak AT levels during fitusiran prophylaxis
timeFrame: From Day 1 up to Month 4
measure: Emicizumab concentrations in plasma
timeFrame: Up to Month 4 of fitusiran treatment
measure: Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment
timeFrame: From Day 1 up to Month 18
measure: Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores
timeFrame: From approximately Month -2 to Month 19 [end of study (EoS) visit]
measure: Participants' treatment preferences (via the Preference Questionnaire)
timeFrame: At Month 12
measure: Change in participants' pain intensity during the fitusiran treatment period (via the PROMIS v2.0 Pain Intensity 3a questionnaire) over time
timeFrame: From approximately Month - 2 to Month 19 (EoS) visit
measure: Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time
timeFrame: From approximately Month - 2 to Month 19 (EoS) visit
measure: Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time
timeFrame: From approximately Month - 2 to Month 19 (EoS) visit
measure: Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis
timeFrame: From Month 4 up to Month 18 (14-month extension period)
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: