A study of fitusiran (ALN-AT3SC) in hemophilia A and B patients previously receiving factor or bypassing agent prophylaxis

Phase 1

• Conditions: Hemophilia A or Hemophilia B; MedDRA version: 20.0Level: LLTClassification code 10060613Term: Hemophilia A (Factor VIII)System Organ Class: 100000004850; MedDRA version: 20.0Level: LLTClassification code 10060614Term: Hemophilia B (Factor IX)System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-004087-19-Outside-EU/EEA
• Lead Sponsor: Genzyme Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-02
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: A
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

Males =12 years of age.

Severe hemophilia A or B as evidenced by:
a.A central laboratory measurement or documented medical record evidence of FVIII <1% or FIX level =2% at Screening.

A minimum of 2 bleeding episodes requiring BPA treatment within the last 6 months prior to Screening. for patients with inhibitory antibodies to factor VIII or factor IX (Cohort A). A minimum of 1 bleeding episode requiring factor treatment within the last 12 months prior to Screening for patients without inhibitory antibodies to factor VIII or factor IX
(Cohort B).

Must meet either the definition of inhibitor or non-inhibitor patient as below:
Inhibitor:
Use of BPAs for prophylaxis and for any bleeding episodes for at least the last 6 months prior to Screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria:
Inhibitor titer of =0.6 BU/mL at Screening, or
Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence
of 2 consecutive titers =0.6 BU/mL, or
Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence
of anamnestic response
The subgroup of patients in Cohort A patients must additionally meet the following criteria to be eligible to start treatment with fitusiran directly after the screening period:
- Hemophilia B with inhibitory antibody to Factor IX as defined above
- Not responding adequately to BPA treatment (historical ABR =20) prior to enrollment
- In the opinion of the Investigator, with approval of Sponsor Medical Monitor, 6-month BPA prophylaxis period should be omitted.

Non-inhibitor:
Use of factor concentrates for prophylaxis and for any 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 and
No use of bypassing agents to treat bleeding episodes for at least the last 6 months prior to Screening and No history of immune tolerance induction therapy within the past 3
years prior to Screening.

Prescribed prophylactic treatment (documented in the medical or pharmacy records) of hemophilia with factor concentrates or BPAs for at least 6 months prior to Screening; the regimen must be consistent with the approved prescribing information for the product or local recommendations, allowing for adjustment to individual patient response, and designed to decrease spontaneous bleeding.

Adherent to the prescribed prophylactic therapy for at least 6 months prior to Screening per Investigator assessment.

Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of patients under the age of legal consent, per local and national requirements.

Are the trial subjects under 18? yes
Number of subjects for this age range: 7
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

Patients with known co-existing bleeding disorders other than hemophilia A or B

Patients with clinically significant liver disease

Patients known to be HIV positive and have a CD4 count <200 cells/µL

Patients with a history of arterial or venous thromboembolism

Estimated glomerular filtration rate =45 mL/min/1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula)

Patients with a co-existing thrombophilic disorder

Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc

Patients with a history of intolerance to SC injection(s)

Patients with an anticipated or planned need for surgery during the study

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 judgement

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified