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Homozygous Familial Hypercholesterolemia (HoFH)Phase 3HYDRANCT02226198

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

A Phase 3 study testing Rosuvastatin 20mg in people with Homozygous Familial Hypercholesterolemia (HoFH), run by AstraZeneca at 9 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 6 to 17 years
What is being tested?
Rosuvastatin 20mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
9 sitesin 7 countries
Study dates
Nov 2014to Jul 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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:
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 7 countries.

9 sites in 7 countries

Malaysia2 sites

  • Research Site

    Kuala Lumpur

  • Research Site

    Kubang Kerian

Other trials in Malaysia

Netherlands2 sites

  • Research Site

    Amsterdam

  • Research Site

    Goteborg

Other trials in Netherlands

Belgium1 site

  • Research Site

    Brussels (Woluwé-St-Lambert)

Other trials in Belgium

Canada1 site

  • Research Site

    Chicoutimi, Quebec

Other trials in Canada

Denmark1 site

  • Research Site

    København Ø

Other trials in Denmark

Israel1 site

  • Research Site

    Haifa

Other trials in Israel

Taiwan1 site

  • Research Site

    Taipei

Other trials in Taiwan

About this study

Official 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)

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

Read the detailed description

This is a randomized, double-blind, placebo-controlled, multi-center, cross-over study of the efficacy, safety and tolerability rosuvastatin in children and adolescents (aged 6 to <18 years) with homozygous familial hypercholesterolemia (HoFH). The study is designed to assess the efficacy of rosuvastatin 20 mg compared to placebo on lipids, lipoproteins and apolipoproteins in pediatric patients with HoFH. The outcome measures to be assessed include low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides, non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, apolipoprotein B (ApoB), apolipoprotein A 1 (ApoA-1) and ApoB/ApoA-1 following 6 weeks of treatment with rosuvastatin 20 mg or placebo. Pharmacokinetic data of the trough plasma exposure of rosuvastatin will also be assessed in these pediatric patients with HoFH.

Being tested
Rosuvastatin 20mg, Placebo
Keywords
LDL-C, HoFH, Hyperlipidemia
Medical subject headings
Homozygous Familial Hypercholesterolemia, Hyperlipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rosuvastatin 20mgDrug

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

  • PlaceboDrug

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

Study groups in NCT02226198
Study groupRoleWhat they receive
RosuvastatinActive comparator6-week treatment period, and after crossover finished a 12-week efficacy maintenance phase for all patients
Receives: Drug: Rosuvastatin 20mg
PlaceboPlacebo comparator6 weeks treatment during crossover
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

Secondary outcomes (30)

  1. TC (mg/dL)

    Efficacy in terms of total cholesterol (TC)

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

  2. TC (mmol/L)

    Efficacy in terms of total cholesterol (TC)

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

  3. Non-HDL C (mg/dL)

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

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

  4. Non-HDL C (mmol/L)

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C)

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

  5. ApoB (mg/dL)

    Efficacy in terms of apolipoprotein B (ApoB)

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

  6. ApoB (g/L)

    Efficacy in terms of apolipoprotein B (ApoB)

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

  7. HDL-C (mg/dL)

    Efficacy in terms of high density lipoprotein cholesterol (HDL C)

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

  8. HDL-C (mmol/L)

    Efficacy in terms of high density lipoprotein cholesterol (HDL C)

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

  9. LDL-C, Not on Apheresis (mg/dL)

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

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

  10. LDL-C, Not on Apheresis (mmol/L)

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) following 6 weeks rosuvastatin 20 mg or placebo treatment in patients not treated with Apheresis

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

  11. LDL-C From End of Placebo (mg/dL)

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

    Measured: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

  12. LDL-C From End of Placebo (mmol/L)

    Change in low density lipoprotein cholesterol (LDL C) from end of placebo period to 6, 12, and 18 weeks of therapy with rosuvastatin 20 mg

    Measured: Samples taken at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18) and Day 168 (week 24)

  13. Trough Concentrations

    Pharmacokinetic profile in terms of trough concentrations. Cross-over phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the cross-over phase. Maintenance phase results based on measurements taken after 6 weeks active treatment (rosuvastatin) in the maintenance phase.

    Measured: Samples taken 24 hours post-dose at Day 42 (week 6), Day 84 (week 12), Day 126 (week 18)

  14. Adverse Events

    Safety and tolerability will be described in terms of frequency and severity of adverse events

    Measured: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

  15. AE's Leading to Discontinuation

    Safety and tolerability will be described in terms of rate of discontinuations due to adverse events

    Measured: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

  16. Abnormal Serum Levels

    Safety and tolerability will be described in terms of abnormal serum laboratory values. The reported parameters are not the only ones measured, but rather those for which abnormailities were found

    Measured: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

  17. Height

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

    Measured: Week 0 (start of cross-over), weeks 6, week 12 and week 18

  18. Height Z-score

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

    Measured: Week 0 (start of cross-over), weeks 6, week 12 and week 18

  19. Weight

    Safety and tolerability will be described in terms of growth, including height (linear growth [cm and standard deviation (SD) score]), and weight.

    Measured: Week 0 (start of cross-over), weeks 6, week 12 and week 18

  20. Tanner Stage

    Stages for fem (Pubic hair, Breasts):

    1. (Preadol,Preadol)
    2. (Sparse, lightly pigmented, medial border of labia,Breast and papilla elevated as small mound; areolar diam incr)
    3. (Darker, beginning to curl, incr amount, Breast and areola enlarged, no contour separation)
    4. (Course, curly, abundant but less amount in adult,Areola and papilla form secondary mound)
    5. (Adult fem triangle, spread to medial surface of thighs,Mature, nipple projects, areola part of general breast contour) For males (Pubic hair, Penis, Testes)

    1=(None,Preadol,Preadol) 2=(Scanty, long, light pigm,Slight enl,Enl scrotum, pink texture alt) 3=(Darker, starts to curl, small amount,Longer,Larger) 4=(Resembles adult type, but less in quant; course, curly,Larger; glans and breadth increased in size,Larger, scrotum dark) 5=(Adult distr, spread to medial thighs,Adult size,Adult size). Progr at a normal rate is preferred. Regr is not preferred.

    Measured: Week 0 (start of cross-over)

  21. TG (mg/dL)

    Efficacy in terms of triglycerides (TG)

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

  22. TG (mmol/L)

    Efficacy in terms of triglycerides (TG)

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

  23. LDL C/HDL C

    Efficacy in terms of low density lipoprotein cholesterol (LDL C) / high density lipoprotein cholesterol (HDL C)

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

  24. TC/HDL C

    Efficacy in terms of total cholesterol (TC) / high density lipoprotein cholesterol (HDL C)

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

  25. Non-HDL C/HDL C

    Efficacy in terms of non-high density lipoprotein cholesterol (non-HDL C) / HDL C

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

  26. ApoB/ApoA

    Efficacy in terms of apolipoprotein B (ApoB) / apolipoprotein A (ApoA)

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

  27. Urinalysis Abnormalitites

    Safety and tolerability will be described in terms of abnormal urine laboratory values

    Measured: Week 0, week 6, week 12 and week 18

  28. ECG Abnormalities

    Safety and tolerability will be described in terms of abnormal electro cardio gram (ECG)

    Measured: Week 0

  29. Physical Exam Abnormalitites

    Safety and tolerability will be described in terms of abnormal physical examinations. Only parameters for which abnormalities were found are reported.

    Measured: Screening, Week 0, week 6, week 12 and week 18, week 24

  30. Abnormal Vital Signs

    Safety and tolerability will be described in terms of abnormal vital signs

    Measured: From screening (5-6weeks before dose) up to the last visit Day 168 (approximately 30 weeks after screening)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2014 (estimated)
  2. Study startNov 2014
  3. Primary completionJul 2015
  4. Study completionJul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02226198
Sponsor's protocol ID
D3561C00004
Acronym
HYDRA
Status last verified
Jul 2016
First submitted
14 Aug 2014
Last updated
4 Jul 2016
Data monitoring committee
No

Publications

  • 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.

    PubMed 28838366

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rosuvastatin 20mg in people with Homozygous Familial Hypercholesterolemia (HoFH), run by AstraZeneca at 9 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Malaysia, Netherlands, Belgium, Canada, Denmark and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

LDL-Cholesterol (mg/dL) (time frame: Samples taken on Day 42 (week 6) and on day 84 (week 12)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02226198, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jul 2016.

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