A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT02226198
• Date of registration: 14/08/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia HYDRA
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Multi-center, Cross-over Study of Rosuvastatin in Children and Adolescents (Aged 6 to <18 Years) With Homozygous Familial Hypercholesterolemia (HoFH)
• Date of first enrolment: November 2014
• Target sample size: 20
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02226198
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Belgium, Canada, Denmark, Germany, Israel, Lebanon, Malaysia, Netherlands, Sweden, Taiwan, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Prior to any study related procedures being performed, provision of written informed
consent from a parent/both parents or guardian and statement of assent from the child
or adolescent (if required by Institutional Review Board [IRB] or Independent Ethics
Committee [EC] according to local regulations and guidelines). Communication between
the Investigator, patient/guardian and child/adolescent to confirm understanding and
required compliance with the requirements of the study.

2. Male and female children and adolescents (aged 6 to <18 years) with at least 1 of the
following criteria:

Documentation of genetic testing confirming 2 mutated alleles of the LDL receptor gene
locus; and/or

Documented untreated LDL C >500 mg/dL (12.9 mmol/L) and triglyceride (TG) <300 mg/dL
(3.4 mmol/L) and at least 1 of the following criteria:

1. Tendinous and/or cutaneous xanthoma prior to 10 years of age; or

2. Documentation of HoFH in both parents by:

- genetic and/or

- clinical criteria

3. Negative pregnancy test (b human chorionic gonadotropin analysis) prior to baseline in
females of child bearing potential:

- Female patients of child bearing potential must adhere to a pregnancy prevention
method (abstinence, chemical, or mechanical) during the study and 3 months
following the last dose.

- Male patients should refrain from fathering a child (including sperm donation)
during the study and up to 3 months following the last dose; and

4. Willing to follow all study procedures including adherence to dietary guidelines,
study visits, fasting blood draws, and compliance with study treatment regimens.

Exclusion Criteria

1. History of statin inducted myopathy or serious hypersensitivity reaction to other HMG
CoA reductase inhibitors (statins), including rosuvastatin, at Visit 1.

2. Fasting serum glucose of >9.99 mmol/L (180 mg/dL) or glycosylated hemoglobin >9% at
Visit 1 or patients with a history of diabetic ketoacidosis within the past year.

3. Uncontrolled hypothyroidism defined as thyroid stimulating hormone (TSH) >1.5 times
the upper limit of normal (ULN) at Visit 1 or patients whose thyroid replacement
therapy was initiated or modified within the last 3 months prior to Visit 2.

4. Current active liver disease or hepatic dysfunction (except a confirmed diagnosis of
Gilbert's disease) as defined as elevations of 1.5 times the upper limit of normal
(ULN) for any age in any of the following liver function tests at Visit 1: Alanine
Aminotransferase (ALT), Aspartate Aminotransferase (AST), or bilirubin.

5. Definite or suspected personal history or family history of clinically significant
adverse drug reactions (ADRs), or hypersensitivity to drugs with a similar chemical
structure to rosuvastatin as well as other statins.



Age minimum: 6 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Homozygous Familial Hypercholesterolemia (HoFH)

Intervention(s)

Drug: Rosuvastatin 20mg

Drug: Placebo

Primary Outcome(s)

LDL-Cholesterol (mmol/L) [Time Frame: Samples taken on Day 42 (week 6) and on day 84 (week 12)]

LDL-Cholesterol (mg/dL) [Time Frame: Samples taken on Day 42 (week 6) and on day 84 (week 12)]

Secondary Outcome(s)

Non-HDL C (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Tanner Stage [Time Frame: Week 0 (start of cross-over)]

ApoB/ApoA [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

HDL-C (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

LDL-C From End of Placebo (mg/dL) [Time Frame: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)]

LDL-C From End of Placebo (mmol/L) [Time Frame: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)]

Abnormal Vital Signs [Time Frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

Abnormal Serum Levels [Time Frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

Non-HDL C/HDL C [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

TC (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

TG (mmol/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Height Z-score [Time Frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18]

TG (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

ApoB (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Height [Time Frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18]

AE's Leading to Discontinuation [Time Frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

LDL C/HDL C [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

TC/HDL C [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Trough Concentrations [Time Frame: Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18)]

Adverse Events [Time Frame: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)]

TC (mmol/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Non-HDL C (mmol/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Physical Exam Abnormalitites [Time Frame: Screening, Week 0, week 6, week 12 and week 18, week 24]

ECG Abnormalities [Time Frame: Week 0]

HDL-C (mmol/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Urinalysis Abnormalitites [Time Frame: Week 0, week 6, week 12 and week 18]

Weight [Time Frame: Week 0 (start of cross-over), weeks 6, week 12 and week 18]

ApoB (g/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

LDL-C, Not on Apheresis (mg/dL) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

LDL-C, Not on Apheresis (mmol/L) [Time Frame: Samples taken at Day 42 (week 6) and Day 84 (week 12)]

Secondary ID(s)

D3561C00004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/07/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02226198