Clinical Trials List
Protocol NumberALN-AT3SC-004 (Sanofi Genzyme EFC14769)
NCT Number(ClinicalTrials.gov Identfier)NCT03417245
2018-03-01 - 2020-05-31
Phase III
Not yet recruiting1
Recruiting6
ICD-10 D68.31
Hemorrhagic disorder due to intrinsic circulating anticoagulants, antibodies, or inhibitors
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
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Genzyme Corporation
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Yen-Lin Liu Division of Pediatrics
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 施銘洋 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Po-Shen Ko Division of Hematology & Oncology
- Giun-Yi Hung Division of Hematology & Oncology
- Jyh-Pyng Gau Division of Hematology & Oncology
- 顏秀如 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- CHING-TIEN PENG Division of Pediatrics
- 巫康熙 Division of Pediatrics
- 翁德甫 Division of Pediatrics
- Yu-Min Liao Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shih-Hsiang Chen Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Hemophilia A or B
Objectives
Primary To evaluate the efficacy of fitusiran compared to on-demand treatment with factorconcentrates, as determined by the frequency of bleeding episodesSecondary To evaluate the efficacy of fitusiran compared to on-demand treatment with factorconcentrates, 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 fitusiranExploratory To evaluate the effects of fitusiran as compared to on-demand treatment with factorconcentrates on the following patient-reported outcomes: Patient satisfaction with treatment Patient activity HRQOL in adolescents (≥12 to <17 years of age) To characterize the pharmacodynamic (PD) effect, pharmacokinetics (PK), andimmunogenicity of fitusiran To evaluate the effects of fitusiran as compared to on-demand treatment with factor concentrates on the total weight-adjusted consumption of factor concentrates To evaluate the effects of fitusiran as compared to on-demand treatment with factorconcentrates on joint status To evaluate the effects of fitusiran as compared to on-demand treatment with factorconcentrates on patient resource use
Test Drug
Fitusiran (ALN-AT3SC)
Active Ingredient
Fitusiran
Dosage Form
injection
Dosage
0.8
Endpoints
Primary
Annualized Bleeding Rate (ABR) in the efficacy period
Secondary
ABR in the treatment period
Annualized spontaneous bleeding rate in the efficacy period
Annualized joint bleeding rate in the efficacy period
Change in Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) physical
health score and total score in the treatment period
ABR in the onset period
Exploratory
Change in the following in the treatment period:
Treatment Satisfaction Questionnaire for Medication (TSQM) domain scores
Hemophilia Activities List (HAL) score
Pediatric HAL (pedHAL) score
EuroQol-5 dimension (EQ-5D) score
Hemophilia Quality of Life Questionnaire for children and adolescents (Haemo-QOL)
score
Hemophilia Joint Health Score (HJHS)
Number of target joint bleeding episodes
Incidence and titer of antidrug antibodies to fitusiran in the fitusiran treatment arm
Antithrombin (AT) activity level over time
Thrombin generation over time
Fitusiran plasma levels
Annualized weight-adjusted use of factor concentrates
Change in patient resource use (eg, work/school attendance, visits to doctor/hospital)
Safety
Incidence, severity, seriousness, and relatedness of adverse events (AEs)
Annualized Bleeding Rate (ABR) in the efficacy period
Secondary
ABR in the treatment period
Annualized spontaneous bleeding rate in the efficacy period
Annualized joint bleeding rate in the efficacy period
Change in Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) physical
health score and total score in the treatment period
ABR in the onset period
Exploratory
Change in the following in the treatment period:
Treatment Satisfaction Questionnaire for Medication (TSQM) domain scores
Hemophilia Activities List (HAL) score
Pediatric HAL (pedHAL) score
EuroQol-5 dimension (EQ-5D) score
Hemophilia Quality of Life Questionnaire for children and adolescents (Haemo-QOL)
score
Hemophilia Joint Health Score (HJHS)
Number of target joint bleeding episodes
Incidence and titer of antidrug antibodies to fitusiran in the fitusiran treatment arm
Antithrombin (AT) activity level over time
Thrombin generation over time
Fitusiran plasma levels
Annualized weight-adjusted use of factor concentrates
Change in patient resource use (eg, work/school attendance, visits to doctor/hospital)
Safety
Incidence, severity, seriousness, and relatedness of adverse events (AEs)
Inclution Criteria
Inclusion Criteria
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the
study:
1. Males ≥12 years of age.
2. Severe hemophilia A or B without inhibitors evidenced by:
a. A central laboratory measurement or documented medical record evidence of
FVIII <1% or FIX level ≤2% at Screening.
b. 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
3. A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last
6 months prior to Screening.
4. 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.
Each patient must meet all of the following inclusion criteria to be eligible for enrollment in the
study:
1. Males ≥12 years of age.
2. Severe hemophilia A or B without inhibitors evidenced by:
a. A central laboratory measurement or documented medical record evidence of
FVIII <1% or FIX level ≤2% at Screening.
b. 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
3. A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last
6 months prior to Screening.
4. 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.
Exclusion Criteria
Exclusion Criteria
Each patient must not meet any of the following exclusion criteria to be eligible for enrollment in
the study:
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
HBs Ag 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/1.73 m2
(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 access, as determined by the Investigator, to allow the blood draws
required by the study protocol.
21. History of intolerance to SC injection(s).
22. Current or future participation in another clinical study, scheduled to occur during this
study, involving an investigational product other than fitusiran or investigational device;
in order to participate in this study, patient must discontinue the investigational product at
least 30 days (or 5× the investigational product half-life, whichever is longer) prior to
dosing (Day 1).
23. Current or prior participation in a gene therapy trial.
24. History of alcohol abuse within the 12 months before Screening. Alcohol abuse is
defined as regular weekly intake of more than 14 units (unit: 1 glass of wine
[approximately 125 mL] = 1 measure of spirits (approximately 1 fluid ounce) = ½ pint of
beer [approximately 284 mL]).
Each patient must not meet any of the following exclusion criteria to be eligible for enrollment in
the study:
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
HBs Ag 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/1.73 m2
(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 access, as determined by the Investigator, to allow the blood draws
required by the study protocol.
21. History of intolerance to SC injection(s).
22. Current or future participation in another clinical study, scheduled to occur during this
study, involving an investigational product other than fitusiran or investigational device;
in order to participate in this study, patient must discontinue the investigational product at
least 30 days (or 5× the investigational product half-life, whichever is longer) prior to
dosing (Day 1).
23. Current or prior participation in a gene therapy trial.
24. History of alcohol abuse within the 12 months before Screening. Alcohol abuse is
defined as regular weekly intake of more than 14 units (unit: 1 glass of wine
[approximately 125 mL] = 1 measure of spirits (approximately 1 fluid ounce) = ½ pint of
beer [approximately 284 mL]).
The Estimated Number of Participants
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Taiwan
25 participants
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Global
120 participants
