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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03417245
Recruitment Status : Active, not recruiting
First Posted : January 31, 2018
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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

Condition or disease Intervention/treatment Phase
Hemophilia A Hemophilia B Drug: fitusiran Drug: factor concentrates Phase 3

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Arm Intervention/treatment
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
Drug: fitusiran
by subcutaneous (SC) injection

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.
Drug: factor concentrates
by intravenous (IV) injection




Primary Outcome Measures :
  1. Annualized bleeding rate (ABR) [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]

Secondary Outcome Measures :
  1. Annualized bleeding rate (ABR) [ Time Frame: at 1 month (onset period) , 9 months (treatment period: 1 month onset period + efficacy period of 8 months) ]
  2. Annualized spontaneous bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
  3. Annualized joint bleeding rate [ Time Frame: 8 months (efficacy period: day 29 to Month 9) ]
  4. 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) ]
  5. Number of participants reported with treatment-emergent adverse events [ Time Frame: 15 months (9 months treatment + 6 months follow up) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03417245


Locations
Show Show 64 study locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
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Study Director: Clinical Sciences & Operations, MD Sanofi
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Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03417245    
Other Study ID Numbers: EFC14769
ALN-AT3SC-004 ( Other Identifier: Alnylam )
2016-001464-11 ( EudraCT Number )
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: September 2020
Individual Participant Data (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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):
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
Coagulants
Fitusiran
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked