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| ID | Type | Description | Link |
|---|---|---|---|
| ALN-AT3SC-002 | Other Identifier | Alnylam | |
| 2015-001395-21 | EudraCT Number | ||
| U1111-1251-5204 | Registry Identifier | ICTRP |
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Primary Objective:
To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B
Secondary Objectives:
It is anticipated that patients in this study will receive treatment with open label fitusiran for approximately 7 years or until fitusiran becomes commercially available, whichever occurs first.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fitusiran | Experimental | Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fitusiran (SAR439774) | Drug | Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc) |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry | Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis |
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Bleeding Rate (ABR) During the Efficacy Period | The ABR was annualized for each participant using the following formula: ABR = total number of bleeding events/total number of days in the respective period x 365.25. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations, MD | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Ann Arbor | Michigan | 48109 | United States | ||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39642315 | Derived | Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900. |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Participants were rolled over from the parent study TDR14767 (NCT02035605).
The study was conducted at 13 centers in 5 countries between 18 September 2015 and 21 March 2023. A total of 34 participants were enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Original Dose Regimen [Safety Analysis Set 1 (SAS 1)] | Participants received fitusiran 50 milligram (mg) or 80 mg subcutaneous (SC) injection every month (QM) under the original dose and regimen. |
| FG001 | Antithrombin (AT)-Based Dose Regimen [Safety Analysis Set 2 (SAS 2)] |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Original Dose Regimen (SAS 1) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 23, 2021 | Mar 12, 2024 |
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Urine samples collected to determine the significant abnormalities in urine. |
| From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG) | Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination | Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes. | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Annualized Spontaneous Bleeding Rate During the Efficacy Period | A spontaneous bleeding episode was defined as a bleeding event that occurred for no apparent or known reason, particularly into the joints, muscles, and soft tissues. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Annualized Joint Bleeding Rate During the Efficacy Period | A joint bleeding episode was defined as an event that is characterized by an unusual sensation in the joint ("aura") in combination with 1) increasing swelling or warmth over the skin over the joint; 2) increasing pain; or 3) progressive loss of range of motion or difficulty in using the limb as compared with baseline. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Time Intervals Between Bleeding Events | Bleed-free duration was defined as the time interval between 2 protocol-defined treated bleeding events, excluding events that occurred during the intercurrent periods. | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX) | Number of coagulation factor injections per bleed was determined. IU= international units, and kg= kilogram. | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa) | Number of BPA injections per bleed was determined. | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC) | Number of BPA injections per bleed was determined. | From Day 29 up to end of the study, maximum of up to 76 months |
| Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24 | The EQ-5D-5L is a standardized and disease-generic instrument for use as a measure of quality of life (QoL) outcome. The EQ-5D-5L consists of 2 parts: EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system included questions for each of following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS recorded participant's self-rated health on a vertical 20-centimeter. VAS scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The EQ-5D-5L questionnaire scores range from 0-100, where 0= worst self-perceived health and 100= best self-perceived health. Positive change from baseline indicates an improvement in QoL. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study. | Baseline and Month 24 |
| Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24 | The Haem-A-QoL questionnaire is psychometrically tested QoL assessment instrument for participants with hemophilia and includes 46 items contributing to 10 QoL domains (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality). Scoring for each item is based on a 5-point Likert scale (1= never, 2= rarely, 3= sometimes, 4= often, and 5= all the time), and the physical health and total transformed scores range from 0 to 100. Higher scores indicated greater impairment. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study. | Baseline and Month 24 |
| Antithrombin Activity Level at the End of Treatment Regimen | The AT activity level was analyzed up to end of treatment regimen. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose. | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Thrombin Generation at the End of Treatment Regimen | The TG data was analyzed by CoagScope and assay performed using calibrated automated thrombogram method. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose. | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
| Maximum Observed Concentration (Cmax) of Fitusiran | Cmax was defined as maximum plasma concentration observed. The non-compartmental Pharmacokinetic (PK) analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
| Time to Reach the Maximum Concentration (Tmax) of Fitusiran | tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
| Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran | AUClast was defined as area under the concentration versus time curve from time 0 to the last measurable concentration. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
| Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran | AUCinf was defined as area under the concentration versus time curve extrapolated to infinity. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
| Terminal Half-Life (t1/2z) of Fitusiran | t1/2z associated with the terminal slope (λz) determined according to the following equation: t1/2z = 0.693/λz; where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi-logarithmic scale. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
| Apparent Total Body Clearance (CL/F) of Fitusiran | CL/F was defined as apparent clearance of study drug from the body. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
| Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran | Vss/F was defined as apparent volume of distribution of study drug at steady state concentration. The non-compartmental PK analysis was performed. | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
| Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration | fe was defined as the amount of fitusiran excreted in urine in 0-24 hour. The non-compartmental PK analysis was performed. | Postdose, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours at Month 24 |
| Pittsburgh |
| Pennsylvania |
| United States |
| Clinical Trial Site | Plovdiv | Bulgaria |
| Clinical Trial Site | Sofia | Bulgaria |
| Clinical Trial Site | Kirov | Russia |
| Clinical Trial Site | Moscow | Russia |
| Clinical Trial Site | Zurich | Switzerland |
| Clinical Trial Site | Basingstoke | United Kingdom |
| Clinical Trial Site | Glasgow | United Kingdom |
| Clinical Trial Site | London | NW3 2QG | United Kingdom |
| Clinical Trial Site | London | SW17 0QT | United Kingdom |
| Clinical Trial Site | Truro | United Kingdom |
Participants received fitusiran 50 mg QM, 80 mg QM or 50 mg every 2 months (Q2M) SC injection under recommended AT-based dose regimen. |
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| NOT COMPLETED |
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| AT-Based Dose Regimen (SAS 2) |
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Safety analysis set 1 included all participants who received at least a partial dose of study drug during the LTE14762 study under the original dose and regimen.
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| ID | Title | Description |
|---|---|---|
| BG000 | Original Dose Regimen (SAS 1) | Participants received fitusiran 50 mg or 80 mg SC injection QM under the original dose and regimen. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race/Ethnicity, Customized | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis. | Safety analysis set (SAS) included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology | Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry | Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis | Urine samples collected to determine the significant abnormalities in urine. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs | Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG) | Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Primary | Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination | Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes. | The SAS included all participants who received at least a partial dose of study drug. | Posted | Count of Participants | Participants | No | From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Bleeding Rate (ABR) During the Efficacy Period | The ABR was annualized for each participant using the following formula: ABR = total number of bleeding events/total number of days in the respective period x 365.25. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). | Full analysis set (FAS) included all participants in SAS. | Posted | Mean | 95% Confidence Interval | bleeding events per year | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Spontaneous Bleeding Rate During the Efficacy Period | A spontaneous bleeding episode was defined as a bleeding event that occurred for no apparent or known reason, particularly into the joints, muscles, and soft tissues. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). | The FAS included all participants in SAS. | Posted | Mean | Standard Deviation | bleeding events per year | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Joint Bleeding Rate During the Efficacy Period | A joint bleeding episode was defined as an event that is characterized by an unusual sensation in the joint ("aura") in combination with 1) increasing swelling or warmth over the skin over the joint; 2) increasing pain; or 3) progressive loss of range of motion or difficulty in using the limb as compared with baseline. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2). | The FAS included all participants in SAS. | Posted | Mean | Standard Deviation | bleeding events per year | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Time Intervals Between Bleeding Events | Bleed-free duration was defined as the time interval between 2 protocol-defined treated bleeding events, excluding events that occurred during the intercurrent periods. | The FAS included all participants in SAS. | Posted | Median | Full Range | days | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX) | Number of coagulation factor injections per bleed was determined. IU= international units, and kg= kilogram. | The FAS included all participants in SAS. Only participants analyzed for specific factor are reported. | Posted | Mean | Standard Deviation | IU/kg per year | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa) | Number of BPA injections per bleed was determined. | The FAS included all participants in SAS. Only participants analyzed for specific factor are reported. | Posted | Mean | Standard Deviation | microgram/kg per year | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
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| Secondary | Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC) | Number of BPA injections per bleed was determined. | The FAS included all participants in SAS. Only participants analyzed for this outcome measure are reported. | Posted | Mean | Standard Deviation | units/kg per year | From Day 29 up to end of the study, maximum of up to 76 months |
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| Secondary | Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24 | The EQ-5D-5L is a standardized and disease-generic instrument for use as a measure of quality of life (QoL) outcome. The EQ-5D-5L consists of 2 parts: EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system included questions for each of following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS recorded participant's self-rated health on a vertical 20-centimeter. VAS scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The EQ-5D-5L questionnaire scores range from 0-100, where 0= worst self-perceived health and 100= best self-perceived health. Positive change from baseline indicates an improvement in QoL. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study. | The FAS included all participants in SAS. Only participants analyzed at baseline and Month 24 are reported. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Month 24 |
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| Secondary | Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24 | The Haem-A-QoL questionnaire is psychometrically tested QoL assessment instrument for participants with hemophilia and includes 46 items contributing to 10 QoL domains (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality). Scoring for each item is based on a 5-point Likert scale (1= never, 2= rarely, 3= sometimes, 4= often, and 5= all the time), and the physical health and total transformed scores range from 0 to 100. Higher scores indicated greater impairment. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study. | The FAS included all participants in SAS. Only participants analyzed at baseline and Month 24 are reported. | Posted | Mean | Standard Deviation | units on a scale | Baseline and Month 24 |
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| Secondary | Antithrombin Activity Level at the End of Treatment Regimen | The AT activity level was analyzed up to end of treatment regimen. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose. | Pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study drug and had at least 1 blood sample collection post dose to determine plasma AT and thrombin generation (TG) levels. | Posted | Mean | Standard Deviation | percentage | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
|
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| Secondary | Thrombin Generation at the End of Treatment Regimen | The TG data was analyzed by CoagScope and assay performed using calibrated automated thrombogram method. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose. | The PD analysis set included all participants who received at least 1 dose of study drug and had at least 1 blood sample collection post dose to determine plasma AT and TG levels. | Posted | Mean | Standard Deviation | nanomoles/liter | From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months) |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Concentration (Cmax) of Fitusiran | Cmax was defined as maximum plasma concentration observed. The non-compartmental Pharmacokinetic (PK) analysis was performed. | Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time to Reach the Maximum Concentration (Tmax) of Fitusiran | tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Median | Full Range | hour | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran | AUClast was defined as area under the concentration versus time curve from time 0 to the last measurable concentration. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | ng*hour/mL | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran | AUCinf was defined as area under the concentration versus time curve extrapolated to infinity. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | ng*h/mL | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Terminal Half-Life (t1/2z) of Fitusiran | t1/2z associated with the terminal slope (λz) determined according to the following equation: t1/2z = 0.693/λz; where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi-logarithmic scale. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | hour | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Apparent Total Body Clearance (CL/F) of Fitusiran | CL/F was defined as apparent clearance of study drug from the body. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | liter per hour | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran | Vss/F was defined as apparent volume of distribution of study drug at steady state concentration. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 blood sample collection post dose to determine plasma concentrations of study drug. Only participants analyzed at each specific time point are reported. | Posted | Mean | Standard Deviation | liter | Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration | fe was defined as the amount of fitusiran excreted in urine in 0-24 hour. The non-compartmental PK analysis was performed. | The PK analysis set included all participants who received at least 1 dose of study drug and have at least 1 urine sample collection post dose to determine urine concentrations of study drug. Only those participants with data available at Month 24 are reported. | Posted | Mean | Standard Deviation | percentage of study drug | Postdose, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours at Month 24 |
|
|
TEAEs data was collected from first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months).
Analysis was performed on the safety analysis set.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Original Dose Regimen (SAS 1) | Participants received fitusiran 50 mg or 80 mg SC injection QM under the original dose and regimen. | 1 | 34 | 13 | 34 | 33 | 34 |
| EG001 | AT-Based Dose Regimen (SAS 2) | Participants received fitusiran 50 mg QM, 80 mg QM or 50 mg Q2M SC injection under recommended AT-based dose regimen. | 0 | 18 | 1 | 18 | 13 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Thrombosis | Cardiac disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastric Ulcer Haemorrhage | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastroduodenal Ulcer | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Haemorrhagic Erosive Gastritis | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Peptic Ulcer Haemorrhage | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Anaemia Postoperative | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Femur Fracture | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Transaminases Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Haemophilic Arthropathy | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hepatocellular Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 25.1 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Subarachnoid Haemorrhage | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood Loss Anaemia | Blood and lymphatic system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Iron Deficiency Anaemia | Blood and lymphatic system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Bundle Branch Block Right | Cardiac disorders | MedDra 25.1 | Systematic Assessment |
| |
| Conjunctivitis Allergic | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Erythema Of Eyelid | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Eye Inflammation | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Retinopathy Hypertensive | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Swelling Of Eyelid | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Visual Impairment | Eye disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Discomfort | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Pain Lower | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Abdominal Tenderness | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Anal Fissure | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Dental Caries | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Diverticulum Intestinal | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Duodenal Ulcer | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Epigastric Discomfort | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Faeces Pale | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Femoral Hernia | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Food Poisoning | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastric Ulcer | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastritis Erosive | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Periodontal Disease | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Chest Discomfort | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Chest Pain | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Influenza Like Illness | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Atrophy | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Discolouration | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Erythema | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Haematoma | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Pain | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Injection Site Swelling | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Peripheral Swelling | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Swelling Face | General disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Allergy To Animal | Immune system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Seasonal Allergy | Immune system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Asymptomatic Covid-19 | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Ear Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Helicobacter Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Herpes Dermatitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Lower Respiratory Tract Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Nail Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Oral Candidiasis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Otitis Media | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Periodontitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Tooth Abscess | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Tooth Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Tracheitis | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Viral Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDra 25.1 | Systematic Assessment |
| |
| Anaemia Postoperative | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Arthropod Bite | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Foot Fracture | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Hyphaema | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Joint Injury | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Ligament Sprain | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Limb Injury | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Muscle Strain | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Paternal Exposure Before Pregnancy | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Post Procedural Erythema | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Post Procedural Oedema | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Post Procedural Swelling | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Procedural Pain | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Thermal Burn | Injury, poisoning and procedural complications | MedDra 25.1 | Systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Blood Lactate Dehydrogenase Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| C-Reactive Protein Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Fibrin D Dimer Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Gamma-Glutamyltransferase Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Haematocrit Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Haemoglobin Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Prostatic Specific Antigen Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Protein Urine Present | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Prothrombin Fragment 1.2 Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Red Blood Cell Count Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Transaminases Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Vitamin D Decreased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Weight Decreased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Weight Increased | Investigations | MedDra 25.1 | Systematic Assessment |
| |
| Glucose Tolerance Impaired | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Impaired Fasting Glucose | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Type 2 Diabetes Mellitus | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Vitamin D Deficiency | Metabolism and nutrition disorders | MedDra 25.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Haemophilic Arthropathy | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Joint Range Of Motion Decreased | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Medial Tibial Stress Syndrome | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Muscle Tightness | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Musculoskeletal Discomfort | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Musculoskeletal Stiffness | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Sacral Pain | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Synovial Cyst | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Synovitis | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Tendon Pain | Musculoskeletal and connective tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cerebral Cyst | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypogeusia | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDra 25.1 | Systematic Assessment |
| |
| Agitated Depression | Psychiatric disorders | MedDra 25.1 | Systematic Assessment |
| |
| Calculus Urinary | Renal and urinary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Chronic Kidney Disease | Renal and urinary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDra 25.1 | Systematic Assessment |
| |
| Testicular Mass | Reproductive system and breast disorders | MedDra 25.1 | Systematic Assessment |
| |
| Testicular Pain | Reproductive system and breast disorders | MedDra 25.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Bronchitis Chronic | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Nasal Obstruction | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Nasal Septum Deviation | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDra 25.1 | Systematic Assessment |
| |
| Dermal Cyst | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hangnail | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Ingrowing Nail | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Keratosis Pilaris | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Palmar Erythema | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Rash Erythematous | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDra 25.1 | Systematic Assessment |
| |
| Pregnancy Of Partner | Social circumstances | MedDra 25.1 | Systematic Assessment |
| |
| Tattoo | Social circumstances | MedDra 25.1 | Systematic Assessment |
| |
| Brachiocephalic Vein Stenosis | Vascular disorders | MedDra 25.1 | Systematic Assessment |
| |
| Collateral Circulation | Vascular disorders | MedDra 25.1 | Systematic Assessment |
| |
| Essential Hypertension | Vascular disorders | MedDra 25.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDra 25.1 | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDra 25.1 | Systematic Assessment |
| |
| Superficial Vein Thrombosis | Vascular disorders | MedDra 25.1 | Systematic Assessment |
|
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi aventis recherche & développement | 800-633-1610 | 6# | Contact-US@sanofi.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 16, 2023 | Mar 12, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| D002836 | Hemophilia B |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
Not provided
Not provided
| ID | Term |
|---|---|
| C000632624 | fitusiran |
Not provided
Not provided
Not provided
| Adverse Event |
|
| Other |
|
| Any Treatment-emergent AESI |
|
| Any TEAE leading to study drug discontinuation |
|
| Any TEAE leading to death |
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
|
|
|
Participants received fitusiran 50 mg QM, 80 mg QM or 50 mg Q2M SC injection under recommended AT-based dose regimen.
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
|
|
|
|
|