Clinical trial NCT03417102: A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients With Inhibitors
Official title: ATLAS-INH: A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients With Hemophilia A or B, With Inhibitory Antibodies to Factor VIII or IX
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Hemophilia B
Keywords: RNAi therapeutic
Hemophilia A
Hemophilia B
Hemophilia A, Severe
Hemophilia B, Severe
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Factor VIII
Factor IX
Inhibitor
Bypassing agents
Coagulants
Fitusiran
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-01-31
Enrollment: 60
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to determine the frequency of bleeding episodes in participants receiving fitusiran as prophylactic treatment of hemophilia compared to participants who were assigned to continue with their regular medication. In addition, the study assessed safety, quality of life, pharmacodynamics (PD), and pharmacokinetics (PK).

Detailed description: The duration of treatment with fitusiran was 9 months. The estimated total time on study, inclusive of screening, for each participant was up to 11 months for all participants who enroll in the extension study and participants in the on-demand arm who did not enroll in the extension study. The estimated total time on study was up to 17 months in fitusiran treatment arm participants who did not enroll in the extension study due to the requirement for up to an additional 6 months of follow-up monitoring for antithrombin levels.

Eligibility criteria: Inclusion Criteria:

* Males, greater than or equal to (\>=) 12 years of age.
* Severe hemophilia A or B with inhibitors.

  * (Severity confirmed by a central laboratory where coagulation factor VIII (FVIII) level was less than (\<)1% or factor IX (FIX) level was less than or equal to \[\<=\]2% at Screening; Inhibitors defined as inhibitor titer of \>=0.6 Bethesda units per milliliter \[BU/mL\] or as evidenced by medical records).
* A minimum of 6 bleeding episodes requiring BPA 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.

Exclusion Criteria:

* Known co-existing bleeding disorders other than hemophilia A or B.
* Antithrombin (AT) activity \<60% at Screening.
* Co-existing thrombophilic disorder.
* Clinically significant liver disease.
* Active hepatitis C virus infection.
* HIV positive with a cluster of differentiation-4 count of \<200 cells/microliter.
* History of arterial or venous thromboembolism.
* Inadequate renal function.
* History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine.
* History of intolerance to SC injection(s).
* Any other conditions or comorbidities that would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgement.

Primary outcomes:
measure: Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
Secondary outcomes:
measure: Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period
timeFrame: From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period
timeFrame: From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Estimated Annualized Spontaneous Bleeding Rate for Treated Bleeds During Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Observed Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Estimated Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Observed Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period
timeFrame: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
measure: Health-related Quality of Life (HRQOL): Change From Baseline in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Month 9
timeFrame: Baseline (Day 1), Month 9
measure: Health-related Quality of Life (HRQOL): Change From Baseline in Haem-A-QOL Total Score at Month 9
timeFrame: Baseline (Day 1), Month 9
measure: Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Onset Period
timeFrame: From Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was the earliest
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Baseline (Day 1) up to 15 months (i.e. 9 months treatment period + 6-months follow-up)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigational Site Number 0117
state: Arizona
city: Los Angeles
country: United States
facility: Investigational Site Number 0139
state: California
city: Orange
country: United States
facility: Investigational Site Number 0135
state: California
city: San Diego
country: United States
facility: Investigational Site Number 0137
state: California
city: Gainesville
country: United States
facility: Investigational Site Number 0128
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 0115
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 0105
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 0103
state: Florida
city: New Orleans
country: United States
facility: Investigational Site Number 0119
state: Louisiana
city: Baltimore
country: United States
facility: Investigational Site Number 0136
state: Maryland
city: Las Vegas
country: United States
facility: Investigational Site Number 0111
state: Nevada
city: Philadelphia
country: United States
facility: Investigational Site Number 0104
state: Pennsylvania
city: Camperdown
country: Australia
facility: Investigational Site Number 6101
city: Clayton
country: Australia
facility: Investigational Site Number 6104
city: Montreal
country: Canada
facility: Investigational Site Number 1102
city: Beijing
country: China
facility: Investigational Site Number 8604
city: Guangzhou
country: China
facility: Investigational Site Number 8602
city: Hangzhou
country: China
facility: Investigational Site Number 8605
city: Shanghai
country: China
facility: Investigational Site Number 8603
city: Tianjin
country: China
facility: Investigational Site Number 8601
city: Lyon
country: France
facility: Investigational Site Number 3303
city: Rouen
country: France
facility: Investigational Site Number 3301
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 4905
city: Leipzig
country: Germany
facility: Investigational Site Number 4906
city: Bangalore
country: India
facility: Investigational Site Number 9102
city: India
country: India
facility: Investigational Site Number 9108
city: Jaipur
country: India
facility: Investigational Site Number 9104
city: Lucknow
country: India
facility: Investigational Site Number 9106
city: Pune
country: India
facility: Investigational Site Number 9103
city: Pune
country: India
facility: Investigational Site Number 9111
city: Vellore
country: India
facility: Investigational Site Number 9105
city: Florence
country: Italy
facility: Investigational Site Number 3901
city: Padua
country: Italy
facility: Investigational Site Number 3904
city: Japan
country: Japan
facility: Investigational Site Number 8110
city: Kita Kyushu-Shi
country: Japan
facility: Investigational Site Number 8103
city: Daejeon
country: Korea, Republic of
facility: Investigational Site Number 8202
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 8203
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 8204
city: Kota Kinabalu
country: Malaysia
facility: Investigational Site Number 6003
city: Malaysia
country: Malaysia
facility: Investigational Site Number 6004
city: Parktown
country: South Africa
facility: Investigational Site Number 2701
city: Polokwane
country: South Africa
facility: Investigational Site Number 2703
city: Port Elizabeth
country: South Africa
facility: Investigational Site Number 2702
city: Madrid
country: Spain
facility: Investigational Site Number 3402
city: Changhua
country: Taiwan
facility: Investigational Site Number 8803
city: Taipei
country: Taiwan
facility: Investigational Site Number 8801
city: Taiwan
country: Taiwan
facility: Investigational Site Number 8804
city: Taiwan
country: Taiwan
facility: Investigational Site Number 8805
city: Adana
country: Turkey
facility: Investigational Site Number 9002
city: Akdeniz
country: Turkey
facility: Investigational Site Number 9004
city: Ankara
country: Turkey
facility: Investigational Site Number 9001
city: Istanbul
country: Turkey
facility: Investigational Site Number 9005
city: Izmir
country: Turkey
facility: Investigational Site Number 9003
city: Turkey
country: Turkey
facility: Investigational Site Number 9006
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8001
city: Lviv
country: Ukraine
facility: Investigational Site Number 8002
city: London
country: United Kingdom
facility: Investigational Site Number 4407
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations, MD
role: STUDY_DIRECTOR
References:
citation: The Lancet Haematology. The role of conferences in tackling inequalities. Lancet Haematol. 2022 Feb;9(2):e81. doi: 10.1016/S2352-3026(22)00008-4. No abstract available.
citation: Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.