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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-004287-30 | EudraCT Number |
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This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).
The primary objective of this study was to evaluate the safety of intravenous (IV) infusions of sebelipase alfa in a more broad population of LAL-D participants than previously studied. Such participants may have been excluded from enrollment in other studies of LAL-D because of age, disease progression, previous treatment by hematopoietic stem cell or liver transplantation, less common disease manifestations, or disease characteristics that would preclude participation in a placebo-controlled study. This open-label study included infants >8 months, children, and adults. At least 4 participants in the study were to be between the age of 2 and 4 years. Eligible participants received sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sebelipase Alfa | Experimental | Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sebelipase Alfa | Drug | IV infusion of sebelipase alfa |
|
| Measure | Description | Time Frame |
|---|---|---|
| Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) | The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received. | Screening, Week 144 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change In Serum Lipids From Baseline To Week 144 | The effect of sebelipase alfa on lipid metabolism was evaluated by measuring the change from baseline to Week 144 in 4 serum lipids: low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); non-HDL-C; triglycerides. Blood samples for these clinical laboratory tests were collected at scheduled time points and analyzed by a central laboratory. |
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Key Inclusion Criteria:
Participant was >8 months of age at the time of dosing.
Confirmation of LAL-D diagnosis as determined by the central laboratory or, for participants with prior hematopoietic stem cell transplant or liver transplant, historical enzyme activity or molecular genetic testing confirming a diagnosis of LAL-D.
Participants >8 months but <4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
Participants ≥4 years of age at Screening had at least 1 of the following documented clinical manifestations of LAL-D:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chicago | Illinois | 60611 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35442238 | Derived | Burton BK, Sanchez AC, Kostyleva M, Martins AM, Marulkar S, Abel F, Baric I. Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2022 Jun 1;74(6):757-764. doi: 10.1097/MPG.0000000000003452. Epub 2022 Apr 19. |
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All participants began treatment with sebelipase alfa at a dose of 1 milligram/kilogram (mg/kg) every other week (qow). Individual participants could escalate/decrease their dose at any time during the study and only at the discretion of the Investigator and in consultation with the Sponsor. All 5 different doses are presented as Milestones below.
A total of 21 study centers were initiated in 15 countries, including Australia, Belgium, Brazil, Canada, Croatia, Denmark, Germany, Italy, Mexico, Netherlands, Russia, Spain, Turkey, United Kingdom (UK), and the United States. Seventeen study centers screened at least 1 participant in all of these countries, except the UK and the Netherlands.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2-<4 Years | This subgroup is part of the full analysis set and includes only participants between the ages of 2 and 4 years old who initiated intravenous (IV) treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Dec 7, 2015 | Dec 6, 2018 |
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| Baseline, Week 144 |
| Participants Testing Positive For Anti-drug Antibodies (ADAs) | The impact of ADAs on the safety and immunogenicity of sebelipase alfa was evaluated by testing for ADAs in participants who received sebelipase alfa in this open-label study. Blood samples for assessment were collected prior to study infusions at Week 2, Week 4, Week 8, Week 12, and every 12 weeks thereafter. Participants testing positive for ADAs were also tested for the presence of neutralizing antibodies that inhibited sebelipase alfa enzyme activity and/or cellular uptake. Any participant experiencing a moderate or severe infusion-associated reaction (IAR) was to have an additional assessment of ADAs at the next study visit (prior to study drug infusion); these participants were to also have serum samples collected at 1 to 2 hours after IAR onset and at the next study visit (prior to study drug infusion) for analysis of serum tryptase. The count of participants who became ADA positive and who tested positive for neutralizing antibodies are presented. | Week 144 |
| Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants | To evaluate the effects of sebelipase alfa on growth parameters in pediatric participants (≤18 years old) presenting with evidence of growth delay, the percent change in the anthropometric parameter of BMI-for-age percentile from Baseline to Week 144 is reported. Anthropometric parameters were plotted on standard growth curves. When possible, historical data on growth parameters was also incorporated into the analyses. Percentiles and Z-scores for BMI-for-age were determined using standard growth charts appropriate to a participant's age on the date of the assessment: the World Health Organization standard growth chart for participants ≤2 years of age and the Centers for Disease Control standard growth chart for participants >2 years of age. | Baseline, Week 144 |
| Shift In Child-Pugh Status From Baseline To Week 144 | In order to evaluate the effects of sebelipase alfa on liver function, the number of participants with a shift in Child-Pugh status from Baseline to Week 144 is reported. The status is based on the Child-Pugh score, which is used in clinical practice to assess prognosis in individuals with chronic liver disease. Laboratory data were used in derivation of the score by summing individual scores (scored 1-3, with 3 indicating most severe) from clinical laboratory test results and physical examinations, including total serum bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The total score was used to determine the Child-Pugh status, reported as Class A (score of 5 or 6), Class B (score of 7 to 9), or Class C (score of 10 to 15). Higher scores and higher categories represented a worse outcome. Data reported as 1 of 2 types of shifts in class: No Change from Baseline; Decline from Baseline. | Baseline, Week 144 |
| Shreveport |
| Louisiana |
| 71103 |
| United States |
| Cincinnati | Ohio | 45229 | United States |
| Westmead | NSW 2145 | Australia |
| Brussels | 1200 | Belgium |
| São Paulo | 04024-002 | Brazil |
| Halifax | Nova Scotia | B3H 1V7 | Canada |
| Zagreb | 10000 | Croatia |
| Copenhagen | 2100 | Denmark |
| Freiburg im Breisgau | 79106 | Germany |
| Padova | 35128 | Italy |
| Mexico City | 06720 | Mexico |
| Amsterdam | 1105 | Netherlands |
| Moscow | 117997 | Russia |
| A Coruña | 15006 | Spain |
| Barcelona | 08036 | Spain |
| Madrid | 28046 | Spain |
| Balcalı | 01300 | Turkey (Türkiye) |
| Birmingham | B4 6NH | United Kingdom |
| FG001 | 4-18 Years | This subgroup is part of the full analysis set and includes only participants between the ages of 4 and 18 years old who initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg qw was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| FG002 | >18 Years | This subgroup is part of the full analysis set and includes only participants greater than 18 years old. This subgroup is part of the full analysis set and includes only participants greater than 18 years old who initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg qw was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| Received at Least 1 Dose of Study Drug |
|
| Received 0.35 mg/kg QOW |
|
| Received 1 mg/kg QOW | All participants started the study at this dose. |
|
| Received 1 mg/kg QW |
|
| Received 3 mg/kg QOW |
|
| Received 3 mg/kg QW |
|
| Completed 96-week Treatment Period |
|
| COMPLETED | Participants who transitioned to commercial product are displayed as having completed the study. |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Sebelipase Alfa | Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg qw was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| 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 | Participants Experiencing Severe Treatment-emergent Adverse Events (TEAEs) | The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received. | Full Analysis Set: All participants who received at least 1 infusion of sebelipase alfa. The full analysis set was used for analysis of safety and efficacy. | Posted | Count of Participants | Participants | Screening, Week 144 |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Percent Change In Serum Lipids From Baseline To Week 144 | The effect of sebelipase alfa on lipid metabolism was evaluated by measuring the change from baseline to Week 144 in 4 serum lipids: low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); non-HDL-C; triglycerides. Blood samples for these clinical laboratory tests were collected at scheduled time points and analyzed by a central laboratory. | Full Analysis Set: All participants who received at least 1 infusion of sebelipase alfa. The full analysis set was used for analysis of safety and efficacy. | Posted | Median | Full Range | Percent Change | Baseline, Week 144 |
| |||||||||||||||||||||||||||||||||
| Secondary | Participants Testing Positive For Anti-drug Antibodies (ADAs) | The impact of ADAs on the safety and immunogenicity of sebelipase alfa was evaluated by testing for ADAs in participants who received sebelipase alfa in this open-label study. Blood samples for assessment were collected prior to study infusions at Week 2, Week 4, Week 8, Week 12, and every 12 weeks thereafter. Participants testing positive for ADAs were also tested for the presence of neutralizing antibodies that inhibited sebelipase alfa enzyme activity and/or cellular uptake. Any participant experiencing a moderate or severe infusion-associated reaction (IAR) was to have an additional assessment of ADAs at the next study visit (prior to study drug infusion); these participants were to also have serum samples collected at 1 to 2 hours after IAR onset and at the next study visit (prior to study drug infusion) for analysis of serum tryptase. The count of participants who became ADA positive and who tested positive for neutralizing antibodies are presented. | Full Analysis Set: All participants who received at least 1 infusion of sebelipase alfa. The full analysis set was used for analysis of safety and efficacy. | Posted | Count of Participants | Participants | Week 144 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Percent Change In Body Mass Index (BMI)-For-Age Percentile From Baseline To Week 144 In Pediatric Participants | To evaluate the effects of sebelipase alfa on growth parameters in pediatric participants (≤18 years old) presenting with evidence of growth delay, the percent change in the anthropometric parameter of BMI-for-age percentile from Baseline to Week 144 is reported. Anthropometric parameters were plotted on standard growth curves. When possible, historical data on growth parameters was also incorporated into the analyses. Percentiles and Z-scores for BMI-for-age were determined using standard growth charts appropriate to a participant's age on the date of the assessment: the World Health Organization standard growth chart for participants ≤2 years of age and the Centers for Disease Control standard growth chart for participants >2 years of age. | Full Analysis Set: All pediatric participants who received at least 1 infusion of sebelipase alfa. The full analysis set was used for analysis of safety and efficacy. | Posted | Mean | Standard Deviation | Percent Change | Baseline, Week 144 |
| |||||||||||||||||||||||||||||||||
| Secondary | Shift In Child-Pugh Status From Baseline To Week 144 | In order to evaluate the effects of sebelipase alfa on liver function, the number of participants with a shift in Child-Pugh status from Baseline to Week 144 is reported. The status is based on the Child-Pugh score, which is used in clinical practice to assess prognosis in individuals with chronic liver disease. Laboratory data were used in derivation of the score by summing individual scores (scored 1-3, with 3 indicating most severe) from clinical laboratory test results and physical examinations, including total serum bilirubin, serum albumin, prothrombin time, ascites, and hepatic encephalopathy. The total score was used to determine the Child-Pugh status, reported as Class A (score of 5 or 6), Class B (score of 7 to 9), or Class C (score of 10 to 15). Higher scores and higher categories represented a worse outcome. Data reported as 1 of 2 types of shifts in class: No Change from Baseline; Decline from Baseline. | Full Analysis Set: All participants who received at least 1 infusion of sebelipase alfa. The full analysis set was used for analysis of safety and efficacy. | Posted | Count of Participants | Participants | Baseline, Week 144 |
|
Screening (up to 45 days prior to start of treatment) to Week 144.
All serious and non-serious AE data are displayed by the study drug administered at the time of AE onset.
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 | 0.35 mg/kg QOW | This reporting group is based on the safety set and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 0.35 mg/kg qow. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG001 | 1.0 mg/kg QOW | This reporting group is based on the safety set and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 1.0 mg/kg qow. | 0 | 31 | 8 | 31 | 30 | 31 |
| EG002 | 1.0 mg/kg QW | This reporting group is based on the safety set and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 1.0 mg/kg qw. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG003 | 3.0 mg/kg QOW | This reporting group is based on the safety set and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 3.0 mg/kg qow. | 0 | 11 | 3 | 11 | 10 | 11 |
| EG004 | 3.0 mg/kg QW | This reporting group is based on the safety set and includes AEs with onset during the administration of IV treatment of sebelipase alfa at a dose of 3.0 mg/kg qw. | 0 | 4 | 0 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Device breakage | Product Issues | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Liver transplant | Surgical and medical procedures | MedDRA 20.1 | Systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Macrocytosis | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Left ventricular dilatation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Left ventricular hypertrophy | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Delayed puberty | Endocrine disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Oral contusion | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Tongue eruption | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vaccination site erythema | General disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Allergy to arthropod bite | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Acute sinusitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Gastritis viral | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Molluscum contagiosum | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Otitis media acute | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pharyngotonsillitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Respiratory tract infection viral | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Tracheitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Varicella zoster virus infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Bone contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Face injury | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Low density lipoprotein increased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Protein total decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
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| Balanoposthitis | Reproductive system and breast disorders | MedDRA 20.1 | Systematic Assessment | Only male participants were exposed to this adverse event. |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
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Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alexion Pharmaceuticals Inc. | Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 17, 2016 | Dec 6, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D015223 | Wolman Disease |
| D016464 | Lysosomal Storage Diseases |
| D015217 | Cholesterol Ester Storage Disease |
| D008659 | Metabolic Diseases |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D052439 | Lipid Metabolism Disorders |
| D007232 | Infant, Newborn, Diseases |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000603932 | Sebelipase alfa |
Not provided
Not provided
Not provided
| >18 years |
|
| Unknown or Not Reported |
|
This subgroup is part of the full analysis set and includes only participants between the ages of 4 and 18 years old who initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg qw was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| OG002 | >18 Years | This subgroup is part of the full analysis set and includes only participants greater than 18 years old. This subgroup is part of the full analysis set and includes only participants greater than 18 years old who initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg qw was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
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