Clinical trial NCT03754790: Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX
Official title: An Open-label, Long-term Safety and Efficacy Study of Fitusiran in Patients With 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: 2018-11-27
Enrollment: 281
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To characterize the long-term safety and tolerability of fitusiran

Secondary Objectives:

* To characterize the efficacy and long-term efficacy of fitusiran as assessed by the frequency of:

  * Bleeding episodes
  * Spontaneous bleeding episodes
  * Joint bleeding episodes
* To characterize the effects of fitusiran on health-related quality of life (HRQOL) measures in participants ≥17 years of age

Detailed description: The estimated total time on the study for a participant is up to 90 months (including screening, treatment period and safety follow up period).

Eligibility criteria: Inclusion criteria :

* Participant must be at least 12 years of age inclusive, at the time of signing the informed consent
* Participants with severe hemophilia A or B who have completed a Phase 3 fitusiran clinical trial
* Male
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant's legally authorized representative

Exclusion criteria:

* Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional factor concentrate or BPA infusion for postoperative hemostasis
* Current participation in immune tolerance induction treatment (ITI)
* Current use of factor concentrates or bypassing agents (BPAs) as regularly administered prophylaxis designed to prevent spontaneous bleeding episodes except for participants requiring factor concentrates or BPAs prophylaxis during the study dosing pause period
* Use of compounds other than factor concentrates or BPAs for hemophilia treatment
* Current or prior participation in a gene therapy trial
* Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) \>1.5 × upper limit of normal reference range (ULN) for patients who are naïve to fitusiran at study start; ALT and/or AST \> 5 x ULN for patients who were in the fitusiran arm in the parent study
* Additional exclusions for participants not currently participating in a fitusiran trial at the time of enrollment in the lower dose cohort:

  * Clinically significant liver disease
  * History of arterial or venous thromboembolism

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 treatment emergent adverse events (TEAEs)
timeFrame: from study baseline (day 1) up to maximum 88 months
Secondary outcomes:
measure: Annualized bleeding rate (ABR)
timeFrame: from first ever dose of fitusiran (day 1) up to maximum 78 months
measure: Annualized spontaneous bleeding rate
timeFrame: from first ever dose of fitusiran (day 1) up to maximum 78 months
measure: Annualized joint bleeding rate
timeFrame: from first ever dose of fitusiran (day 1) up to maximum 78 months
measure: Changes in Haem-A-quality of life (QoL) score
timeFrame: from first ever dose of fitusiran (day 1) up to maximum 78 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital Site Number : 8400009
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles Site Number : 8400019
state: California
city: Orange
country: United States
facility: Center for Inherited Blood Disorders (CIBD) Site Number : 8400016
state: California
city: Jacksonville
country: United States
facility: Nemours Children's Clinic Site Number : 8400008
state: Florida
city: Tampa
country: United States
facility: St Joseph's Children's Hospital of Tampa Site Number : 8400002
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center -1725 W Harrison St Site Number : 8400001
state: Illinois
city: Boston
country: United States
facility: ~Massachusetts General Hospital Site Number : 8400011
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital - 1500 E Medical Center Dr Site Number : 8400012
state: Michigan
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases Site Number : 8400007
state: Nevada
city: Akron
country: United States
facility: Childrens Hospital Medical Center of Akron Site Number : 8400006
state: Ohio
city: Camperdown
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Prahran
country: Australia
facility: Investigational Site Number : 0360003
state: Victoria
city: Murdoch
country: Australia
facility: Investigational Site Number : 0360002
state: Western Australia
city: Montreal
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Beijing
country: China
facility: Investigational Site Number : 1560004
city: Beijing
country: China
facility: Investigational Site Number : 1560007
city: Changsha
country: China
facility: Investigational Site Number : 1560014
city: Chengdu
country: China
facility: Investigational Site Number : 1560009
city: Guangzhou
country: China
facility: Investigational Site Number : 1560002
city: Guiyang
country: China
facility: Investigational Site Number : 1560011
city: Hangzhou
country: China
facility: Investigational Site Number : 1560005
city: Jinan
country: China
facility: Investigational Site Number : 1560008
city: Kunming
country: China
facility: Investigational Site Number : 1560012
city: Lanzhou
country: China
facility: Investigational Site Number : 1560013
city: Qingdao
country: China
facility: Investigational Site Number : 1560010
city: Shanghai
country: China
facility: Investigational Site Number : 1560003
city: Suzhou
country: China
facility: Investigational Site Number : 1560006
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Lyon
country: France
facility: Investigational Site Number : 2500002
city: Paris
country: France
facility: Investigational Site Number : 2500003
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Leipzig
country: Germany
facility: Investigational Site Number : 2760003
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480002
city: Bangalore
country: India
facility: Investigational Site Number : 3560001
city: Lucknow
country: India
facility: Investigational Site Number : 3560005
city: Mumbai
country: India
facility: Investigational Site Number : 3560007
city: Pune
country: India
facility: Investigational Site Number : 3560002
city: Pune
country: India
facility: Investigational Site Number : 3560010
city: Ranipet
country: India
facility: Investigational Site Number : 3560004
city: Crumlin
country: Ireland
facility: Investigational Site Number : 3720001
state: Dublin
city: Dublin
country: Ireland
facility: Investigational Site Number : 3720002
city: Ramat Gan
country: Israel
facility: Investigational Site Number : 3760001
city: Milano
country: Italy
facility: Investigational Site Number : 3800002
state: Lombardia
city: Padua
country: Italy
facility: Investigational Site Number : 3800004
state: Veneto
city: Nishinomiya
country: Japan
facility: Investigational Site Number : 3920002
state: Hyogo
city: Isehara
country: Japan
facility: Investigational Site Number : 3920005
state: Kanagawa
city: Kitakyushu
country: Japan
facility: Investigational Site Number : 3920003
city: Nagoya
country: Japan
facility: Investigational Site Number : 3920001
city: Saitama
country: Japan
facility: Investigational Site Number : 3920004
city: Tokyo
country: Japan
facility: Investigational Site Number : 3920008
city: Busan
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Busan-gwangyeoksi
city: Daejeon
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Daejeon-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
city: Ampang
country: Malaysia
facility: Investigational Site Number : 4580003
city: Johor Bahru
country: Malaysia
facility: Investigational Site Number : 4580001
city: Kota Kinabalu
country: Malaysia
facility: Investigational Site Number : 4580002
city: Port Elizabeth
country: South Africa
facility: Investigational Site Number : 7100002
city: Changhua
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580008
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580004
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580005
city: Taoyuan City
country: Taiwan
facility: Investigational Site Number : 1580007
city: Adana
country: Turkey
facility: Investigational Site Number : 7920002
city: Akdeniz
country: Turkey
facility: Investigational Site Number : 7920004
city: Bornova
country: Turkey
facility: Investigational Site Number : 7920012
city: Gaziantep
country: Turkey
facility: Investigational Site Number : 7920006
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920005
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
city: Kayseri
country: Turkey
facility: Investigational Site Number : 7920008
city: Samsun
country: Turkey
facility: Investigational Site Number : 7920007
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040001
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040003
city: Lviv
country: Ukraine
facility: Investigational Site Number : 8040002
city: Mykolaiv
country: Ukraine
facility: Investigational Site Number : 8040004
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
city: Glasgow
country: United Kingdom
facility: Investigational Site Number : 8260004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: