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 (ATLAS-OLE)

• ClinicalTrials.gov Identifier: NCT03754790
• Recruitment Status: Recruiting
• First Posted: November 27, 2018
• Last Update Posted: March 4, 2021
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: November 25, 2018
• First Posted Date: November 27, 2018
• Last Update Posted Date: March 4, 2021
• Actual Study Start Date: January 9, 2019
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 26, 2018): Number of patients with adverse events [ Time Frame: From day -30 (screening) to day 673 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 3, 2021)

• Annualized bleeding rate (ABR) [ Time Frame: From day 29 to day 673 ]
  Annualized bleeding rate (ABR) in the treatment period
• Annualized spontaneous bleeding rate [ Time Frame: From day 29 to day 673 ]
  Annualized spontaneous bleeding rate in the treatment period
• Annualized joint bleeding rate [ Time Frame: From day 29 to day 673 ]
  Annualized joint bleeding rate in the treatment period
• Changes in Haem-A-quality of life (QoL) score [ Time Frame: On day 1 (baseline), day 169, day 337, day 505 and day 673 ]
  Change in Haem A QoL physical health score and total score in the treatment period (in participants ≥17 years of age) from baseline (day 1) to day 169 (post-restart for patients on the modified dosing regimen), day 337, day 505 and day 673

Original Secondary Outcome Measures (submitted: November 26, 2018)

• Annualized bleeding rate (ABR) [ Time Frame: From day 29 to day 673 ]
  Annualized bleeding rate (ABR) in the treatment period
• Annualized spontaneous bleeding rate [ Time Frame: From day 29 to day 673 ]
  Annualized spontaneous bleeding rate in the treatment period
• Annualized joint bleeding rate [ Time Frame: From day 29 to day 673 ]
  Annualized joint bleeding rate in the treatment period
• Changes in Haem-A-quality of life (QoL) score [ Time Frame: On day 1 (baseline), day 337 and day 673 ]
  Change in Haem A QoL physical health score and total score in the treatment period (in participants ≥17 years of age) from baseline (day 1) to day 337 and day 673

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

Descriptive Information

• Brief Title: 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

Brief Summary

Primary Objective:

To characterize the long-term safety and tolerability of fitusiran

Secondary Objectives:

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

  • Bleeding episodes
  • Spontaneous bleeding episodes
  • Target 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 study for each participant is up to 56 months which consists of a screening period of up to 60 days, an open label treatment period of up to 48 months and a follow up period of up to 6-month after the last dose of fitusiran
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hemophilia

Intervention

Drug: Fitusiran

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Study Arms

Experimental: Fitusiran

Participants will be administered fitusiran as an subcutaneous injection once monthly or every other month for 48 months

Intervention: Drug: Fitusiran

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 26, 2018): 244
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2026
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

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
• 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext 1 then #; Contact-US@sanofi.com

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

Administrative Information

• NCT Number: NCT03754790
• Other Study ID Numbers: LTE15174; 2018-002880-25 ( EudraCT Number ); U1111-1210-0018 ( Other Identifier: UTN )
• 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
• Product Manufactured in and Exported from the U.S.: 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; Sanofi

• PRS Account: Sanofi
• Verification Date: March 2021