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Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia (ORION-13)

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ClinicalTrials.gov Identifier: NCT04659863
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : October 19, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C).

Condition or disease Intervention/treatment Phase
Familial Hypercholesterolemia - Homozygous Drug: Inclisiran Drug: Placebo Phase 3

Detailed Description:
This is a two-part (1 year double-blind inclisiran versus placebo / 1 year open-label inclisiran) multicenter study designed to evaluate safety, tolerability, and efficacy of inclisiran in adolescents with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective is to evaluate the effect of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel (Year 1) to single-group (Year 2)
Masking: Double (Participant, Investigator)
Masking Description: Masked (Year 1) to No Masking (Year 2)
Primary Purpose: Treatment
Official Title: Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Adolescents (12 to Less Than 18 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-13)
Actual Study Start Date : February 16, 2021
Estimated Primary Completion Date : November 14, 2022
Estimated Study Completion Date : December 7, 2023


Arm Intervention/treatment
Experimental: Inclisiran
Year 1 - inclisiran sodium 300 mg subcutaneous injection (given at Days 1, 90, and 270) Day 360 only - placebo subcutaneous injection Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 450 and 630)
Drug: Inclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection
Other Name: KJX839

Placebo Comparator: Placebo
Year 1 - placebo subcutaneous injection (given at Days 1, 90 and 270) Year 2 - inclisiran sodium 300 mg subcutaneous injection (given at Days 360, 450, and 630)
Drug: Placebo
Sterile normal saline (0.9% sodium chloride in water for injection) for subcutaneous injection
Other Name: Saline solution




Primary Outcome Measures :
  1. Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 [ Time Frame: Baseline and Day 330 ]
    Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [percent change] at Day 330 (Year 1)


Secondary Outcome Measures :
  1. Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 [ Time Frame: Baseline, after Day 90 up to Day 330 ]
    Evaluate the effect of inclisiran compared to placebo on reducing LDL-C [time-adjusted percent change] over Year 1

  2. % change and absolute change in LDL-C from baseline up to Day 720 [ Time Frame: Baseline, up to Day 720 ]
    Evaluate the effect of inclisiran compared to placebo (for Year 1) and long-term (up to Day 720), on lowering LDL-C over time

  3. % change and absolute change in other lipoprotein and lipid parameters from baseline up to Day 720 [ Time Frame: Baselne, up to Day 720 ]
    Evaluate the effect of inclisiran compared to placebo (up to Day 330) and long-term (up to Day 720), on lowering apolipoprotein B (Apo B), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein A1 (Apo A1) over time

  4. % change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720 [ Time Frame: Baseline, up to Day 720 ]
    Evaluate the effect of inclisiran compared to placebo (up to Day 330) and long-term (up to Day 720), on lowering PCSK9 over time



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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous Familial Hypercholesterolemia (HoFH) diagnosed by genetic confirmation
  • Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening
  • On maximally tolerated dose of statin (investigator's discretion) with or without other lipid-lowering therapy; stable for ≥ 30 days before screening
  • Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 at screening

Exclusion Criteria:

  • Documented evidence of a null (negative) mutation in both LDLR alleles
  • Heterozygous familial hypercholesterolemia (HeFH)
  • Active liver disease
  • Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome
  • Major adverse cardiovascular events within 1 month prior to randomization
  • Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)
  • Treatment with mipomersen or lomitapide (within 5 months of screening)
  • Recent and/or planned use of other investigational medicinal products or devices

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04659863


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Florida
Excel Medical Clinical Trials LLC Recruiting
Boca Raton, Florida, United States, 33434
Contact    561-756-8206    sjbaum@fpim.org   
Principal Investigator: Seth Baum, MD         
Canada
Novartis Investigative Site Recruiting
Quebec, Canada, G1V 4W2
France
Novartis Investigative Site Recruiting
Bron Cedex, France, 69677
Greece
Novartis Investigative Site Recruiting
Ioannina, GR, Greece, 455 00
Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Genovefa Kolovou, MD    +30 210 4807139    genovefa@kolovou.com   
Lebanon
Novartis Investigative Site Recruiting
Ashrafieh, Lebanon, 166830
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1105 AZ
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3015 GD
Slovenia
Novartis Investigative Site Recruiting
Ljubljana, Slovenia, 1000
Switzerland
Novartis Investigative Site Recruiting
Geneve 14, Switzerland, 1211
Turkey
Novartis Investigative Site Recruiting
Istanbul, TUR, Turkey, 34098
Novartis Investigative Site Recruiting
Izmir, Turkey, 35040
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04659863    
Other Study ID Numbers: CKJX839C12302
2020-002755-38 ( EudraCT Number )
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: October 19, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Homozygous familial hypercholesterolemia (HoFH)
LDL-cholesterol (LDL-C)
adolescents
pediatric
small interfering ribonucleic acid (siRNA)
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias