A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors

• ClinicalTrials.gov Identifier: NCT03417245
• Recruitment Status: Active, not recruiting
• First Posted: January 31, 2018
• Last Update Posted: December 7, 2020
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: January 25, 2018
• First Posted Date: January 31, 2018
• Last Update Posted Date: December 7, 2020
• Actual Study Start Date: March 1, 2018
• Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 1, 2020): Annualized bleeding rate (ABR) [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
• Original Primary Outcome Measures (submitted: January 30, 2018): Annualized bleeding rate (ABR) [ Time Frame: 9 months ]

Current Secondary Outcome Measures (submitted: September 1, 2020)

• Annualized bleeding rate (ABR) [ Time Frame: at 1 month (onset period) , 9 months (treatment period: 1 month onset period + efficacy period of 8 months) ]
• Annualized spontaneous bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
• Annualized joint bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
• Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score on a scale of 0-100 with higher scores representing greater impairment [ Time Frame: 9 months (treatment period: 1 month onset period + efficacy period of 8 months) ]
• Number of participants reported with treatment-emergent adverse events [ Time Frame: 15 months (9 months treatment + 6 months follow up) ]

Original Secondary Outcome Measures (submitted: January 30, 2018)

• Annualized spontaneous bleeding rate [ Time Frame: 9 months ]
• Annualized joint bleeding rate [ Time Frame: 9 months ]
• Haem-A-QOL Questionnaire [ Time Frame: 9 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
• Official Title: ATLAS-A/B: A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients With Hemophilia A or B, Without Inhibitory Antibodies to Factor VIII or IX

Brief Summary

Primary Objective:

-To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by the frequency of bleeding episodes

Secondary Objectives:

• To evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by:

  • The frequency of spontaneous bleeding episodes
  • The frequency of joint bleeding episodes
  • Health-related quality of life (HRQOL) in patients ≥17 years of age
• To determine the frequency of bleeding episodes during the onset period
• To determine the safety and tolerability of fitusiran

Detailed Description

The duration of treatment with fitusiran is 9 months. The estimated total time on study, inclusive of Screening, for each patient is up to 11 months for all patients who enroll in the extension study and patients in the on-demand arm who do not enroll in the extension study. The estimated total time on the study may be up to 17 months in fitusiran treatment arm patients who do not enroll in the extension study due to the requirement for an additional 6 months of follow-up monitoring for antithrombin levels.

Patients who complete the study may be eligible for an open-label extension study LTE15174 (NCT03754790)

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hemophilia A
• Hemophilia B

Intervention

• Drug: fitusiran
  by subcutaneous (SC) injection
• Drug: factor concentrates
  by intravenous (IV) injection

Study Arms

• Experimental: fitusiran
  Fitusiran administered subcutaneously (SC) as prophylaxis once monthly, with use of on-demand factor concentrates for treatment of breakthrough bleeding episodes. All patients will be treated for a total of 9 months
  Intervention: Drug: fitusiran
• Experimental: On demand factor concentrates
  On-demand factor concentrates for treatment of breakthrough bleeding episodes. On-demand use of factor concentrates is defined as the use of these agents, as needed, for episodic bleeding, and not on a regular regimen intended to prevent spontaneous bleeding. All patients will be treated for a total of 9 months.
  Intervention: Drug: factor concentrates

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 30, 2018): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2021
• Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males, ≥12 years of age

• Severe hemophilia A or B without inhibitors

  • Severity confirmed by a central laboratory where FVIII level is <1% or FIX level is ≤2% at Screening;

  • On-demand use of factor concentrate to manage bleeding episodes for at least the last 6 months prior to Screening, and meet each of the following criterion:

    • Nijmegen modified Bethesda assay inhibitor titer of <0.6 BU/mL at Screening
    • No use of BPAs to treat bleeding episodes for at least the last 6 months prior to Screening
    • No history of immune tolerance induction therapy within the last 3 years prior to Screening
• A minimum of 6 bleeding episodes requiring factor concentrate 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, i.e. Von Willebrand's disease, additional factor deficiencies, or platelet disorders
• Antithrombin (AT) activity <60% at Screening
• Co-existing thrombophilic disorder
• Clinically significant liver disease
• Active HCV infection
• HIV positive with a CD4 count of <200 cells/μL
• 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 (GalNAc)
• History of intolerance to SC injection(s)
• Any other conditions or comorbidities that would make the patient unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgment

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Bulgaria, Portugal, Russian Federation

Administrative Information

• NCT Number: NCT03417245
• Other Study ID Numbers: EFC14769; ALN-AT3SC-004 ( Other Identifier: Alnylam ); 2016-001464-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Study Sponsor: Genzyme, a Sanofi Company
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations, MD; Sanofi

• PRS Account: Sanofi
• Verification Date: December 2020