E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A or Hemophilia B |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia is an inherited bleeding disorder in which the blood does not clot normally and can result in internal bleeding into the muscles and joints. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of ALN AT3SC in male patients with moderate or severe hemophilia A or B. |
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E.2.2 | Secondary objectives of the trial |
To investigate the long-term efficacy of ALN-AT3SC, characterize the safety and efficacy of concomitantly administered factor VIII (FVIII) or factor IX (FIX) and ALN-AT3SC for treatment of bleeding episodes, antithrombin (AT) reduction and thrombin generation (TG) increase, the pharmacokinetics (PK) of ALN AT3SC, and assess changes in health-related quality of life (QOL) over time. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Completed and tolerated study drug dosing in study ALN-AT3SC-001.
Male aged ≥18 years.
Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%.
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E.4 | Principal exclusion criteria |
Liver disease defined as clinically significant cirrhosis as determined by the Investigator, INR >1.5 at Screening, ALT/AST >3× upper limit of the normal reference range (ULN), platelet count ≤120,000/mL and/or other complete blood count test results that are considered clinically significant and unacceptable by the Investigator, or known hepatitis C virus currently requiring treatment with ribavirin or interferon.
Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/µL at screening.
History of venous thromboembolism.
Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity.
Uncontrolled hypertension.
Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation.
If using nonsteroidal anti-inflammatory drugs intermittently or chronically, must tolerate them with no previous side effects. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety assessments will include monitoring for AEs (including serious AEs [SAEs]), clinical laboratory evaluations (including hematology, biochemistry, urinalysis, and coagulation), vital signs, 12-lead electrocardiogram (ECG), antidrug antibodies, and physical examinations. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The PK of ALN-AT3SC, evaluated by:
•plasma PK profiles of ALN-AT3C determined at specified time points
•Urine collected (spot collection and pooled) to determine the amount
PD effect of ALN-AT3SC, evaluated by the following biomarkers:
•Plasma AT levels (activity and antigen-based).
•Plasma TG as determined by the calibrated automated thrombogram (CAT) assay. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
Switzerland |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |