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

Hemophilia Clinical Trial

— ATLAS-OLE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03754790
• Other study ID #: LTE15174
• Secondary ID: U1111-1210-00182
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 9, 2019
• Est. completion date: November 5, 2026

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 281
• Est. completion date: November 5, 2026
• Est. primary completion date: November 5, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia
• Hemophilia A

Intervention

Drug:
• Fitusiran
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Denmark,  France,  Germany,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  South Africa,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment emergent adverse events (TEAEs)	The number of participants experiencing any TEAEs, serious TEAEs, discontinuation due to TEAEs and death will be reported	from study baseline (day 1) up to maximum 88 months
Secondary	Annualized bleeding rate (ABR)	Annualized bleeding rate (ABR) in the treatment period	from first ever dose of fitusiran (day 1) up to maximum 78 months
Secondary	Annualized spontaneous bleeding rate	Annualized spontaneous bleeding rate in the treatment period	from first ever dose of fitusiran (day 1) up to maximum 78 months
Secondary	Annualized joint bleeding rate	Annualized joint bleeding rate in the treatment period	from first ever dose of fitusiran (day 1) up to maximum 78 months
Secondary	Changes in Haem-A-quality of life (QoL) score	Change in Haem A QoL physical health score and total score in the treatment period (in participants =17 years of age) from first ever dose of fitusiran (day 1) to month 48	from first ever dose of fitusiran (day 1) up to maximum 78 months