Clinical Trial Results:
Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of Evolocumab for LDL-C Reduction, as Add-on to Diet and Lipid-lowering Therapy, in Pediatric Subjects From 10 to 17 Years of Age With Heterozygous Familial Hypercholesterolemia (HeFH) or Homozygous (HAUSER-OLE)
|
Summary
|
|
EudraCT number |
2015-002276-25 |
Trial protocol |
DE GB NO HU AT BE CZ GR ES NL PT SI PL IT RO |
Global end of trial date |
01 Jun 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
18 Nov 2021
|
First version publication date |
18 Nov 2021
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
20120124
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02624869 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Amgen Inc.
|
||
Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
|
||
Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH., MedInfoInternational@amgen.com
|
||
Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH., MedInfoInternational@amgen.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-001268-PIP01-12 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
01 Jun 2021
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
01 Jun 2021
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The main objective of this study is to describe the safety and tolerability of 80 weeks of subcutaneous (SC) evolocumab when added to standard of care in children 10 to 17 years of age with familial hypercholesterolemia.
|
||
Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines.
The study protocol and all amendments, the informed consent form, and any accompanying materials provided to the subjects were reviewed and approved by an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) at each study center.
The investigator or his/her designee informed the subject or legally acceptable representative of all aspects pertaining to the subject’s participation in the study and obtained written informed consent from the subject or legally acceptable representative before any screening procedures were performed or any investigational product(s) were administered.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Sep 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Canada: 17
|
||
Country: Number of subjects enrolled |
United States: 3
|
||
Country: Number of subjects enrolled |
Austria: 10
|
||
Country: Number of subjects enrolled |
Belgium: 5
|
||
Country: Number of subjects enrolled |
Czechia: 5
|
||
Country: Number of subjects enrolled |
Greece: 1
|
||
Country: Number of subjects enrolled |
Hungary: 10
|
||
Country: Number of subjects enrolled |
Italy: 25
|
||
Country: Number of subjects enrolled |
Netherlands: 22
|
||
Country: Number of subjects enrolled |
Norway: 6
|
||
Country: Number of subjects enrolled |
Poland: 4
|
||
Country: Number of subjects enrolled |
Portugal: 1
|
||
Country: Number of subjects enrolled |
Russian Federation: 1
|
||
Country: Number of subjects enrolled |
Slovenia: 1
|
||
Country: Number of subjects enrolled |
Spain: 4
|
||
Country: Number of subjects enrolled |
Switzerland: 3
|
||
Country: Number of subjects enrolled |
Turkey: 4
|
||
Country: Number of subjects enrolled |
United Kingdom: 3
|
||
Country: Number of subjects enrolled |
Brazil: 20
|
||
Country: Number of subjects enrolled |
Colombia: 6
|
||
Country: Number of subjects enrolled |
Australia: 3
|
||
Country: Number of subjects enrolled |
Malaysia: 1
|
||
Country: Number of subjects enrolled |
South Africa: 8
|
||
Worldwide total number of subjects |
163
|
||
EEA total number of subjects |
94
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
35
|
||
Adolescents (12-17 years) |
120
|
||
Adults (18-64 years) |
8
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||
Recruitment details |
This study was conducted at 46 centers in 23 countries (Australia, Austria, Belgium, Brazil, Canada, Colombia, Czech Republic, Greece, Hungary, Italy, Malaysia, Netherlands, Norway, Poland, Portugal, Russia, Slovenia, South Africa, Spain, Switzerland, Turkey, United Kingdom, and United States of America). | ||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||
Screening details |
This study enrolled participants with heterozygous familial hypercholesterolemia (HeFH) who had completed the parent study 20120123 (EudraCT #: 2014-002277-11) without experiencing a treatment-related serious adverse event or children 10 to 17 years of age with a diagnosis of homozygous familial hypercholesterolemia (HoFH). | ||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||||||
|
Arm title
|
HeFH (Placebo in Parent Study): Evolocumab 420 mg QM | ||||||||||||||||||||||||||||
Arm description |
Participants with heterozygous familial hypercholesterolemia (HeFH) who had received placebo in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Evolocumab
|
||||||||||||||||||||||||||||
Investigational medicinal product code |
AMG 145
|
||||||||||||||||||||||||||||
Other name |
Repatha®
|
||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen, Solution for injection in needle-free injector
|
||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||
Dosage and administration details |
Administered once a month by subcutaneous injection
|
||||||||||||||||||||||||||||
|
Arm title
|
HeFH (Evolocumab in Parent Study): Evolocumab 420 mg QM | ||||||||||||||||||||||||||||
Arm description |
Participants with heterozygous familial hypercholesterolemia who had received evolocumab in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Evolocumab
|
||||||||||||||||||||||||||||
Investigational medicinal product code |
AMG 145
|
||||||||||||||||||||||||||||
Other name |
Repatha®
|
||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen, Solution for injection in needle-free injector
|
||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||
Dosage and administration details |
Administered once a month by subcutaneous injection
|
||||||||||||||||||||||||||||
|
Arm title
|
HoFH: Evolocumab 420 mg QM | ||||||||||||||||||||||||||||
Arm description |
Participants with homozygous familial hypercholesterolemia (HoFH) received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Evolocumab
|
||||||||||||||||||||||||||||
Investigational medicinal product code |
AMG 145
|
||||||||||||||||||||||||||||
Other name |
Repatha®
|
||||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled pen, Solution for injection in needle-free injector
|
||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||||||||||
Dosage and administration details |
Administered once a month by subcutaneous injection
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HeFH (Placebo in Parent Study): Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia (HeFH) who had received placebo in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HeFH (Evolocumab in Parent Study): Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia who had received evolocumab in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HoFH: Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with homozygous familial hypercholesterolemia (HoFH) received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
HeFH (Placebo in Parent Study): Evolocumab 420 mg QM
|
||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia (HeFH) who had received placebo in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks. | ||
Reporting group title |
HeFH (Evolocumab in Parent Study): Evolocumab 420 mg QM
|
||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia who had received evolocumab in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||
Reporting group title |
HoFH: Evolocumab 420 mg QM
|
||
Reporting group description |
Participants with homozygous familial hypercholesterolemia (HoFH) received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Participants with Treatment-emergent Adverse Events (TEAEs) [1] | ||||||||||||||||||||||||||||||||||||||||
End point description |
An adverse event is defined as any untoward medical occurrence in a clinical trial participant, not necessarily having a causal relationship with study treatment.
A serious AE is as an AE that met at least 1 of the following criteria:
• fatal;
• life threatening;
• required in-patient hospitalization or prolongation of existing hospitalization;
• resulted in persistent or significant disability/incapacity;
• congenital anomaly/birth defect;
• other medically important serious event.
AEs were graded for severity using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0:
Grade 1: Mild; asymptomatic or mild symptoms;
Grade 2: Moderate; minimal, local or noninvasive intervention indicated;
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated;
Grade 4: Life-threatening consequences; urgent intervention indicated;
Grade 5: Death related to AE.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From first dose of evolocumab in this study up to and including 30 days after the last dose or up to the end of study date, whichever was earlier; up to 80 weeks.
|
||||||||||||||||||||||||||||||||||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses in this open-label study were descriptive in nature. No statistical inference or missing value imputation was planned. |
|||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percent Change from Baseline to Week 80 in Low-density Lipoprotein Cholesterol (LDL-C) in HeFH Participants [2] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percent Change from Baseline to Week 80 in LDL-C in HoFH Participants [3] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percent Change from Baseline to Week 80 in Non-HDL-C in HeFH Participants [4] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percent Change from Baseline to Week 80 in Non-HDL-C in HoFH Participants [5] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percent Change from Baseline to Week 80 in Apolipoprotein B in HeFH Participants [6] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percent Change from Baseline to Week 80 in Apolipoprotein B in HoFH Participants [7] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percent Change from Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HeFH Participants [8] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percent Change from Baseline to Week 80 in Total Cholesterol/HDL-C Ratio in HoFH Participants [9] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percent Change from Baseline to Week 80 in Apolipoprotein B / Apolipoprotein A1 Ratio in HeFH Participants [10] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percent Change from Baseline to Week 80 in Apolipoprotein B/Apolipoprotein A1 Ratio in HoFH Participants [11] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Change from Baseline to Week 80 in LDL-C in HeFH Participants [12] | ||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value of the parent study 20120123.
Results are reported for the full analysis set with available data.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||
| Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Change from Baseline to Week 80 in LDL-C in HoFH Participants [13] | ||||||||
End point description |
For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline and week 80
|
||||||||
| Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Results are reported separately for subjects with HeFH and HoFH. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Estradiol Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Testosterone Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Follicle Stimulating Hormone (FSH) Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Luteinizing Hormone (LH) Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Adenocorticotropic Hormone (ACTH) Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Dehydroepiandrosterone Sulfate (DHEA-S) Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Cortisol Levels | ||||||||||||||||
End point description |
For HeFH participants baseline was defined as the baseline value in the parent study 20120123. For HoFH participants baseline was defined as the baseline value in this study (20120124).
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Participants with Liver Function Test Abnormalities at Week 80 | ||||||||||||||||||||||||
End point description |
Liver function tests included alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels and total bilirubin levels.
Results are reported for the full analysis set with available data.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Week 80
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Number of Participants with Abnormalities in Levels of Creatine Kinase (CK) at Week 80 | ||||||||||||||||||||
End point description |
The number of participants with levels of creatine kinase greater than 5 times the upper limit of normal (ULN) and greater than 10 times the ULN, measured by the central laboratory.
Results are reported for the full analysis set with available data.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 80
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||
End point title |
Change from Baseline to Week 80 in Carotid Intima-media Thickness (cIMT) | ||||||||||||||||
End point description |
Carotid intima-media thickness measures the thickness of the intima and media, the inner two layers of the carotid artery, and is used to determine the extent of plaque buildup in the walls of the arteries (atherosclerosis) supplying blood to the head.
CIMT was measured by ultrasonography and analyzed at a core laboratory.
The largest values measured in the left common carotid artery (LCCA) and the right common carotid artery (RCCA) are averaged in this analysis.
Results are reported for the full analysis set with available data.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Height at Weeks 24, 48, and 80 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Results are reported for the full analysis set with available data at each time point.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and weeks 24, 48, and 80
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Weight at Weeks 24, 48, and 80 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Results are reported for the full analysis set with available data at each time point.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and weeks 24, 48, and 80
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Number of Participants with Change in Tanner Staging from Baseline to Week 80 | ||||||||||||||||||||||||||||
End point description |
Pubertal growth and sexual maturity was assessed separately for males and females using the 5 Tanner stages where stage 1 = prepubertal and stage 5 = mature.
Results are reported for the full analysis set.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline and week 80
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of evolocumab in this study up to and including 30 days after the last dose or up to the end of study date, whichever was earlier; up to 80 weeks.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HeFH (Placebo in Parent Study): Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia (HeFH) who had received placebo in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks (QM) for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HeFH (Evolocumab in Parent Study): Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with heterozygous familial hypercholesterolemia who had received evolocumab in the parent study received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HoFH: Evolocumab 420 mg QM
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants with homozygous familial hypercholesterolemia (HoFH) received 420 mg evolocumab administered by subcutaneous injection every 4 weeks for up to 80 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
10 Sep 2015 |
• Added safety endpoint of incidence of abnormal neurological examination at week 80.
• Changed endpoint of change from baseline in cognitive function at week 80 as assessed by Cogstate battery from an exploratory endpoint to a safety endpoint.
• Added that adverse device effects and disease related events would be collected at every study visit.
• Added collection of sample for assessment of fasting vitamins A, D, E, and K levels.
• Deleted papilla elevation from tanner stages (sexual maturity ratings) for stage 1 male genital size. |
||
22 Jun 2016 |
• Clarified primary endpoint timepoint at week 80.
• Added language that defines baseline lab values for rollover and de novo subjects.
• Clarified eligibility criteria; rollover subjects should not have experienced treatment related serious adverse events in Study 20120123.
• Updated schedule of assessments and study procedures:
- allowed for a 4 week screening window for rollover subjects and for those subjects who exceed the 4-week window noted which procedures must be redone;
- updated collection points for creatinine kinase;
- added additional analytes for urinalysis;
- removed thyroid stimulating hormone (TSH) as an analyte. |
||
26 Apr 2017 |
• Updated the number of sites expected.
• Added AMD product information and option for device use.
• Clarified enrollment should be on day 1 or as close as possible to day 1 and no earlier than 5 days prior to day 1.
• Aligned safety definitions and reporting procedures with current protocol template. |
||
27 May 2020 |
• Added interim analysis for all enrolled subjects.
• Updated number of subjects expected to roll over from Study 20120123 into Study 20120124.
• Aligned with current protocol template:
- removed language regarding the collection of disease related events;
- removed details from study monitoring and data collection to restrict Amgen (or designee) correcting obvious data errors in the clinical trial database. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
