A study of fitusiran (ALN-AT3SC) in hemophilia A and B patients without inhibitors

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2016-001464-11-DE
• Date of registration: 02/01/2018
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: A study of fitusiran (ALN-AT3SC) in hemophilia A and B patients without inhibitors
• Scientific 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
• Date of first enrolment: 19/05/2020
• Target sample size: 199
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001464-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Rescue SOC; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Bulgaria, Canada, China, Denmark, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Portugal, Russian Federation, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Project Management
• Affiliation: PPD Global

• Name: Project Management
• Affiliation: PPD Global

Key inclusion & exclusion criteria

Inclusion criteria:
Males =12 years of age.

Severe hemophilia A or B (evidenced by a central laboratory FVIII <1% or FIX level =2% at Screening) without inhibitors (evidenced by inhibitor titer of <0.6 BU/mL and supported by medical records)

AT activity =60% at Screening

A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 171
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Known co-existing bleeding disorders other than hemophilia A or B, ie, Von Willebrand’s disease, additional factor deficiencies, or platelet disorders.
2. Current use of factor concentrates as regularly administered prophylaxis designed to prevent spontaneous bleeding episodes.
3. AT activity <60% at Screening as determined by central laboratory measurement.
4. Presence of clinically significant liver disease, or as indicated by any of the conditions below:
a. INR >1.2;
b. ALT and/or AST >1.5× upper limit of normal reference range (ULN);
c. Total bilirubin >ULN (>1.5 ULN in patients with Gilbert’s Syndrome);
d. History of portal hypertension, esophageal varices, or hepatic encephalopathy;
e. Presence of ascites by physical exam
5. Hepatitis C virus antibody positive, except patients with a history of HCV infection who meet both conditions a. and b.:
a. Completed curative treatment at least 12 weeks prior to enrollment and attained sustained virologic response as documented by a negative HCV RNA at screening, or they have spontaneously cleared infection as documented by negative HCV RNA at Screening.
b. No evidence of cirrhosis according to one of the following assessments:
? FibroScan <12.5 kPa (where available), or
? FibroTest score <0.75 and APRI <2 (if FibroScan unavailable)
6. Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
7. Presence of acute or chronic hepatitis B infection (IgM anti-HBc antibody positive or HBsAg positive).
8. Platelet count =100,000/µL.
9. Presence of acute infection at Screening.
10. Known to be HIV positive with CD4 count <200 cells/µL.
11. Estimated glomerular filtration rate =45 mL/min/1.73m2 (using the Modification of Diet in Renal Disease [MDRD] formula).
12. Co-existing thrombophilic disorder, as determined by presence of any of the below as identified at central laboratory (or via historical results, where available):
a. FV Leiden (homozygous or heterozygous)
b. Protein S deficiency
c. Protein C deficiency
d. Prothrombin mutation (G20210A; homozygous or heterozygous)
13. History of antiphospholipid antibody syndrome.
14. History of arterial or venous thromboembolism, atrial fibrillation, significant valvular disease, myocardial infarction, angina, transient ischemic attack, or stroke. Patients who have experienced thrombosis associated with indwelling venous access may be enrolled.
15. Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin that has been successfully treated.
16. Any condition (eg, medical concern), which in the opinion of the Investigator, would make the patient unsuitable for dosing on Day 1 or which could interfere with the study compliance, the patient’s safety and/or the patient’s participation in the completion of the treatment period of the study. This includes significant active and poorly controlled (unstable) cardiovascular, neurologic, gastrointestinal, endocrine, renal or psychiatric disorders unrelated to hemophilia identified by key laboratory abnormalities or medical history.
17. At Screening, anticipated need of surgery during the study or planned surgery scheduled to occur during the study.
18. Completion of a surgical procedure within 14 days prior to Screening, or currently receiving additional factor infusion for postoperative hemostasis.
19. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
20. Inadequate venous ac

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Hemophilia A or Hemophilia B
MedDRA version: 20.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850

Intervention(s)

Product Name: fitusiran
Product Code: SAR439774
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fitusiran
CAS Number: 1609016-97-8
Current Sponsor code: SAR439774
Other descriptive name: ALN-57213
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Through 9 months

Secondary Objective: 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 in patients, and health related quality of life (HRQOL) in patients receiving fitusiran.

Primary end point(s): Annualized bleeding rate (ABR)

Secondary Outcome(s)

Secondary end point(s): ABR in the treatment period
Annualized spontaneous bleeding rate in the efficacy period
Annualized joint bleeding rate in the efficacy period
Change in Haem-A-QOL physical health score and total score in the treatment period
ABR in the onset period

Timepoint(s) of evaluation of this end point: Through 9 months

Secondary ID(s)

2016-001464-11-IE

EFC14769

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date: 19/05/2020
Contact: