Clinical trial NCT05662319: A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia
Official title: A Phase 3, Single-arm, Multicenter, Multinational, Open-label, One-way Crossover Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged ≥ 12 Years With Severe Hemophilia A or B With or Without Inhibitory Antibodies to Factor VIII or IX
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hemophilia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-12-22
Enrollment: 79
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: CROSSOVER
Intervention model description: One way cross-over
Primary purpose: TREATMENT

Brief summary: This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia.

The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment.

The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include:

* A screening period up to approximately 60 days,
* A standard of care (SOC) period of approximately 6 study months (24 weeks),
* A fitusiran treatment period of approximately 36 study months (144 weeks),
* An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery.

The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study


Eligibility criteria: Inclusion Criteria:

* Diagnosis of severe congenital hemophilia A or B (FVIII \<1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
* For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
* Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements

Exclusion Criteria:

* Known co-existing bleeding disorders other than congenital hemophilia A or B
* History of arterial or venous thromboembolism, not associated with an indwelling venous access
* History of intolerance to SC injection(s).
* Current participation in immune tolerance induction therapy (ITI)
* Prior gene therapy
* Current or prior participation in a fitusiran trial
* Current or prior participation in a gene therapy trial
* Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
* Presence of clinically significant liver disease AT activity \<60% at Screening
* Co-existing 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: Annualized bleeding rate (ABR) in the fitusiran primary efficacy period
timeFrame: Day 169 to Day 505 (since the first dose of fitusiran)
Secondary outcomes:
measure: Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on prophylaxis standard of care (SOC) in the SOC period
timeFrame: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
measure: Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on on-demand standard of care (SOC) in the SOC period
timeFrame: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
measure: Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC period
timeFrame: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
measure: Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC period
timeFrame: Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period)
measure: Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis
timeFrame: Day 1 (D1) to Day 505, and from D1 to Day 1009, and during SOC from Day-168 to D-1
measure: Annualized bleeding rate (ABR) in the fitusiran 18-month efficacy period
timeFrame: Day 1 to Day 505
measure: Annualized bleeding rate (ABR) in the fitusiran 36-month treatment period
timeFrame: Day 1 to Day 1009
measure: Annualized weight-adjusted consumption of CFC/BPA
timeFrame: Day -168 until Day 1009
measure: Number of participants with adverse events
timeFrame: Date of signed ICF (Day -228 to Day -169) until last visit (approximately 50 months after date of signed ICF)
Other outcomes:
Locations:
city: Orange
country: United States
facility: Center for Inherited Blood Disorders (CIBD) Site Number : 8400012
state: California
city: San Diego
country: United States
facility: University of California San Diego Site Number : 8400011
state: California
city: Minneapolis
country: United States
facility: University of Minnesota Site Number : 8400016
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Site Number : 8400009
state: New Jersey
city: New Hyde Park
country: United States
facility: Northwell Health Hemostasis and Thrombosis Center Site Number : 8400015
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Site Number : 8400001
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh-4401 Penn Ave Site Number : 8400017
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center of Dallas Site Number : 8400018
state: Texas
city: Houston
country: United States
facility: The Gulf States Hemophilia and Thrombophilia Center Site Number : 8400002
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah Health Sciences Center Site Number : 8400006
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Site Number : 8400007
state: Wisconsin
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Hamilton
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Beijing
country: China
facility: Investigational Site Number : 1560003
city: Guangzhou
country: China
facility: Investigational Site Number : 1560001
city: Jinan
country: China
facility: Investigational Site Number : 1560002
city: Kremlin Bicetre
country: France
facility: Investigational Site Number : 2500003
city: Lille
country: France
facility: Investigational Site Number : 2500002
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760002
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000003
city: Bangalore
country: India
facility: Investigational Site Number : 3560004
city: Bhubaneswar
country: India
facility: Investigational Site Number : 3560007
city: Pune-411011
country: India
facility: Investigational Site Number : 3560001
city: Punjab
country: India
facility: Investigational Site Number : 3560006
city: Vellore
country: India
facility: Investigational Site Number : 3560003
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800003
state: Lombardia
city: Milano
country: Italy
facility: Investigational Site Number : 3800001
city: Roma
country: Italy
facility: Investigational Site Number : 3800002
city: Kashihara-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Nara
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Nagoya
country: Japan
facility: Investigational Site Number : 3920003
city: Saitama-shi
country: Japan
facility: Investigational Site Number : 3920002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840002
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840004
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840001
city: Lodz
country: Poland
facility: Investigational Site Number : 6160004
state: Lódzkie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160002
state: Malopolskie
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Jeddah
country: Saudi Arabia
facility: Investigational Site Number : 6820002
city: Benoni
country: South Africa
facility: Investigational Site Number : 7100003
city: Parktown
country: South Africa
facility: Investigational Site Number : 7100001
city: La Coruña
country: Spain
facility: Investigational Site Number : 7240002
state: A Coruña [La Coruña]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
state: Madrid, Comunidad De
city: Zaragoza
country: Spain
facility: Investigational Site Number : 7240003
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580003
city: Adana
country: Turkey
facility: Investigational Site Number : 7920002
city: Akdeniz
country: Turkey
facility: Investigational Site Number : 7920004
city: Capa
country: Turkey
facility: Investigational Site Number : 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: