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

NCT02226198 | Completed Phase 3 Results

• 1 other identifier: D3561C00004
• Study Type: interventional
• Target: 20
• Locations: 7 countries
• Sites: 9

Brief Summary

The purpose of the study is to establish the efficacy, safety and tolerability of rosuvastatin in children and adolescents with homozygous familial hypercholesterolemia.

Conditions

Homozygous Familial Hypercholesterolemia (HoFH)

Keywords

LDL-C; HoFH; Hyperlipidemia

Outcome Measures

Primary Outcomes (2)

• LDL-Cholesterol (mg/dL)

  Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment

  Samples taken on Day 42 (week 6) and on day 84 (week 12)

• LDL-Cholesterol (mmol/L)

  Change in low density lipoprotein cholesterol (LDL C) following 6 weeks of rosuvastatin 20 mg compared to 6 weeks of placebo treatment

  Samples taken on Day 42 (week 6) and on day 84 (week 12)

Secondary Outcomes (30)

• TC (mg/dL)

  Samples taken at Day 42 (week 6) and Day 84 (week 12)

• TC (mmol/L)

  Samples taken at Day 42 (week 6) and Day 84 (week 12)

• Non-HDL C (mg/dL)

  Samples taken at Day 42 (week 6) and Day 84 (week 12)

• Non-HDL C (mmol/L)

  Samples taken at Day 42 (week 6) and Day 84 (week 12)

• ApoB (mg/dL)

  Samples taken at Day 42 (week 6) and Day 84 (week 12)

Study Arms (2)

Rosuvastatin

ACTIVE COMPARATOR

6-week treatment period, and after crossover finished a 12-week efficacy maintenance phase for all patients

Drug: Rosuvastatin 20mg

Placebo

PLACEBO COMPARATOR

6 weeks treatment during crossover

Drug: Placebo

Interventions

Rosuvastatin 20mg DRUG

Active drug will be taken taken orally, QD, either in the morning or in the evening

Rosuvastatin

Placebo DRUG

Will be taken taken orally, QD, either in the morning or in the evening

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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:
• Tendinous and/or cutaneous xanthoma prior to 10 years of age; or
• Documentation of HoFH in both parents by:
• genetic and/or
• clinical criteria
• 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
• Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.

You may not qualify if:

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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (9)

Research Site

Brussels (Woluwé-St-Lambert), Belgium

Location

Research Site

Chicoutimi, Quebec, Canada

Location

Research Site

København Ø, Denmark

Location

Research Site

Haifa, Israel

Location

Research Site

Kuala Lumpur, Malaysia

Location

Research Site

Kubang Kerian, Malaysia

Location

Research Site

Amsterdam, Netherlands

Location

Research Site

Goteborg, Netherlands

Location

Research Site

Taipei, Taiwan

Location

Related Publications (1)

• Stein EA, Dann EJ, Wiegman A, Skovby F, Gaudet D, Sokal E, Charng MJ, Mohamed M, Luirink I, Raichlen JS, Sunden M, Carlsson SC, Raal FJ, Kastelein JJP. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations. J Am Coll Cardiol. 2017 Aug 29;70(9):1162-1170. doi: 10.1016/j.jacc.2017.06.058.

  PMID: 28838366 DERIVED

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Hyperlipidemias

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Robin Mukherjee
• Organization: AstraZeneca Plc

robin.mukherjee@astrazeneca.com

+46 31 776 1000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 27, 2014
• Study Start: November 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 4, 2016
• Results First Posted: July 4, 2016

Record last verified: 2016-07

Locations

MY (2); BE (1); DK (1); CA (1); NL (2); IL (1); TW (1)