Clinical Trials List
Protocol NumberALN-AT3SC-009（EFC15110）
NCT Number(ClinicalTrials.gov Identfier)NCT03549871
2019-06-14 - 2021-11-30
Phase III
Recruiting4
Terminated2
ICD-10D68.1
Hereditary factor XI deficiency
ATLAS-PPX: an open-label, multinational, switching study to describe the efficacy and safety of fitusiran prophylaxis in patients with hemophilia A and B previously receiving factor or bypassing agent prophylaxis.
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
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
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- CHING-TIEN PENG Division of Pediatrics
- 巫康熙 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yen-Lin Liu Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shih-Hsiang Chen Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Acquired hemophilia
Objectives
Primary
To characterize the frequency of bleeding episodes while receiving fitusiran treatment, relative to the frequency of
bleeding episodes while receiving factor or bypassing agent (BPA) prophylaxis
Secondary
To characterize the following while receiving fitusiran treatment, relative to receiving factor or BPA prophylaxis:
- 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 characterize the frequency of bleeding episodes during the onset and treatment periods in patients receiving
fitusiran
To characterize the safety and tolerability of fitusiran
To characterize the annualized weight-adjusted consumption of factor/BPA while receiving fitusiran treatment,
relative to receiving factor or BPA prophylaxis
Test Drug
Fitusiran
Active Ingredient
Fitusiran
Dosage Form
Injection
Dosage
80 ml
Endpoints
Primary
Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period
Secondary
Annualized spontaneous bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Annualized joint bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Change in Haem-A-QOL physical health score and total score in the fitusiran treatment period and the factor or
BPA prophylaxis period
ABR in the fitusiran onset period
ABR in fitusiran treatment period
Annualized weight-adjusted consumption of factor/BPA
Annualized Bleeding Rate (ABR) in the fitusiran efficacy period and the factor or BPA prophylaxis period
Secondary
Annualized spontaneous bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Annualized joint bleeding rate in the fitusiran efficacy period and the factor or BPA prophylaxis period
Change in Haem-A-QOL physical health score and total score in the fitusiran treatment period and the factor or
BPA prophylaxis period
ABR in the fitusiran onset period
ABR in fitusiran treatment period
Annualized weight-adjusted consumption of factor/BPA
Inclution Criteria
1. Males ≥12 years of age.
2. Severe hemophilia A or B as evidenced by:
a) A central laboratory measurement at screening or documented medical record evidence of FVIII <1% or FIX level ≤2%.
3. 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).
4. 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.
5. 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.
6. Adherent to the prescribed prophylactic therapy for at least 6 months prior to Screening per Investigator assessment.
7. 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 (The legal age of majority in Taiwan is above 20 years.)
2. Severe hemophilia A or B as evidenced by:
a) A central laboratory measurement at screening or documented medical record evidence of FVIII <1% or FIX level ≤2%.
3. 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).
4. 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.
5. 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.
6. Adherent to the prescribed prophylactic therapy for at least 6 months prior to Screening per Investigator assessment.
7. 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 (The legal age of majority in Taiwan is above 20 years.)
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 participation in immune tolerance induction therapy (ITI).
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) International normalized ratio (INR) >1.2;
b) Alanine transaminase (ALT) and/or aspartate transaminase (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 (immunoglobulin M antibody (IgM) anti-HBc antibody positive or hepatitis B virus surface antigen (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/1.73 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 mutation (homozygous or heterozygous)
b) Protein S deficiency
c) Protein C deficiency
d) Prothrombin mutation (G20210A; homozygous and 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 concentrate or BPA 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 subcutaneously (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 an investigational device; in order to participate in this study, patient must discontinue the investigational product or investigational device 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]).
2. Current participation in immune tolerance induction therapy (ITI).
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) International normalized ratio (INR) >1.2;
b) Alanine transaminase (ALT) and/or aspartate transaminase (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 (immunoglobulin M antibody (IgM) anti-HBc antibody positive or hepatitis B virus surface antigen (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/1.73 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 mutation (homozygous or heterozygous)
b) Protein S deficiency
c) Protein C deficiency
d) Prothrombin mutation (G20210A; homozygous and 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 concentrate or BPA 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 subcutaneously (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 an investigational device; in order to participate in this study, patient must discontinue the investigational product or investigational device 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
20 participants
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Global
70 participants
