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ORION-16: Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04652726
Collaborator
(none)
150
Enrollment
79
Locations
2
Arms
46.4
Anticipated Duration (Months)
1.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
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 heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) on stable standard of care background lipid-lowering therapy. The primary objective is to demonstrate superiority of inclisiran compared to placebo in reducing LDL-C (percent change) at Day 330.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Parallel (Year 1) to single-group (Year 2)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 Heterozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol (ORION-16)
Actual Study Start Date :
Jan 27, 2021
Anticipated Primary Completion Date :
Nov 14, 2023
Anticipated Study Completion Date :
Dec 9, 2024

Arms and Interventions

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 Names:
  • 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 subcutaneous injection)
    Other Names:
  • Saline solution

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 [Baseline and Day 330]

      Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [percent change] at Day 330 (Year 1)

    Secondary Outcome Measures

    1. Time-adjusted % change in LDL-C from baseline after Day 90 and up to Day 330 [Baseline, after Day 90 up to Day 330]

      Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [time-adjusted percent change] over Year 1

    2. Absolute change in LDL-C from baseline to Day 330 [Baseline and Day 330]

      Demonstrate superiority of inclisiran compared to placebo in reducing LDL-C [absolute change] at Day 330 (Year 1)

    3. % change in apolipoprotein B (Apo B), lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol from baseline to Day 330 [Baseline and Day 330]

      Demonstrate superiority of inclisiran compared to placebo in reducing Apo B, lipoprotein (a) [Lp(a)], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol [percent change] at Day 330 (Year 1) - Hierarchical testing

    4. % change and absolute change in LDL-C from baseline up to Day 720 [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

    5. % change and absolute change in other lipoproteins and lipid parameters from baseline up to Day 720 [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 Apo B, Lp(a), 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

    6. % change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720 [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 PCSK9 over time

    Eligibility Criteria

    Criteria

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

    • Heterozygous Familial Hypercholesterolemia (HeFH) diagnosed either by genetic testing or on phenotypic criteria

    • Fasting LDL-C >130 mg/dL (3.4 mmol/L) at screening

    • Fasting triglycerides <400 mg/dL (4.5 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:

    • Homozygous familial hypercholesterolemia (HoFH)

    • Active liver disease

    • Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome

    • Major adverse cardiovascular events within 3 months prior to randomization

    • Previous treatment with monoclonal antibodies directed towards PCSK9 (within 90 days of screening)

    • Recent and/or planned use of other investigational medicinal products or devices

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tucson Medical Center Tucson Arizona United States 85712
    2 Excel Medical Clinical Trials LLC Boca Raton Florida United States 33434
    3 Washington University School of Medicine Saint Louis Missouri United States 63110
    4 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    5 Goryeb Children s Hospital Morristown New Jersey United States 07960
    6 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    7 Wake Forest U of Health Sciences Winston-Salem North Carolina United States 27157
    8 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229-3039
    9 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    10 Childrens Hospital Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
    11 University of Tennessee Health Science Center Memphis Tennessee United States 38163
    12 Primary Children's Medical Center Salt Lake City Utah United States 84113
    13 West Virginia Children's Hospital Morgantown West Virginia United States 26505
    14 American Family Children's Hospital Madison Wisconsin United States 53792
    15 Novartis Investigative Site Woolloongabba Queensland Australia 4102
    16 Unidade de pesquisa clinica - Hospital Universitario Walter Cantidio Fortaleza Ceara Brazil 60430275
    17 Nucleo de Pesquisa Clinica do Rio Grande do Sul Porto Alegre RS Brazil 90430-001
    18 Setor de Lípides, Aterosclerose e Biologia Sao Paulo SP Brazil 04023-900
    19 Heart Institute (InCOr) HCMFUSP Sao Paulo SP Brazil 05403 000
    20 Novartis Investigative Site Vancouver British Columbia Canada V6Z 1Y6
    21 Novartis Investigative Site London Ontario Canada N6A 5A5
    22 Novartis Investigative Site Quebec Canada G1V 4W2
    23 Novartis Investigative Site Zagreb Croatia 10000
    24 Novartis Investigative Site Bron Cedex France 69677
    25 Novartis Investigative Site Toulouse Cedex France 31059
    26 Universitaetsmedizin Mannheim Mannheim Baden-Wuerttemberg Germany 68305
    27 KKIM UK Frankfurt/Main Frankfurt Germany 60590
    28 Universitaetsklinikum Freiburg Freiburg Germany 79106
    29 University General Hospital of Ioannina Ioannina GR Greece 455 00
    30 Hippokrateion General Hospital of Athens Greece Athens Greece 115 27
    31 Metropolitan Hospital Athens Greece 18547
    32 Hippokratiou Hospital, Thessaloniki, Greece Thessaloniki Greece 54642
    33 Novartis Investigative Site Budapest Hungary 1085
    34 Novartis Investigative Site Pecs Hungary 7623
    35 Lipid Research Jerusalem Israel 9112001
    36 Lipids Center Sheba Medical Center, Israel Ramat Gan Israel 52621
    37 Novartis Investigative Site Milano MI Italy 20162
    38 Novartis Investigative Site Modena MO Italy 41124
    39 Novartis Investigative Site Roma RM Italy 00100
    40 Novartis Investigative Site Roma RM Italy 00165
    41 Novartis Investigative Site Irbid Jordan 22110
    42 Hotel Dieu de France Hospital Ashrafieh Lebanon 166830
    43 American University of Beirut Medical Center Beirut Lebanon 1107 2020
    44 UiTM Sungai Buloh Sungai Buloh Selangor Darul Ehsan Malaysia 47000
    45 Novartis Investigative Site Kuala Lumpur Malaysia 59100
    46 Novartis Investigative Site Rotterdam Zuid Holland Netherlands 3015 GD
    47 Novartis Investigative Site Amsterdam Netherlands 1105 AZ
    48 Novartis Investigative Site Oslo Norway 0514
    49 Novartis Investigative Site Gdansk Poland 80 952
    50 Novartis Investigative Site Lodz Poland 93-338
    51 Novartis Investigative Site Kazan Russian Federation 420012
    52 Research Institute for Complex Issues of Cardiovascular Disease Kemerovo Russian Federation 650002
    53 Novartis Investigative Site Moscow Russian Federation 127412
    54 Institute of Internal Prev. Med. Novosibirsk Russian Federation 630090
    55 KK Women's and Children's Hospital Singapore Singapore 229899
    56 University Medical Centre Ljubljana, Div. of Pediatric Dept. of Endocrinology, Diabetes and Metabolic Diseases Ljubljana Slovenia 1000
    57 Novartis Investigative Site Bloemfontein Free State South Africa 9301
    58 Novartis Investigative Site Pretoria Gauteng South Africa 0184
    59 Novartis Investigative Site Somerset West Western Cape South Africa 7130
    60 Novartis Investigative Site Cape Town South Africa 7925
    61 Hospital Reina Sofia Cordoba Andalucia Spain 14004
    62 Hospital Virgen de la Vcitoria Malaga Andalucia Spain 29010
    63 Hospital Universitario Virgen del Rocio Sevilla Andalucia Spain 41013
    64 Hospital Central de Asturias Oviedo Asturias Spain 33011
    65 Hospital Clínic de Barcelona Barcelona Catalunya Spain 08036
    66 Novartis Investigative Site Pamplona Navarra Spain 31008
    67 Hospital Abente y Lago A Coruna Spain 15001
    68 Novartis Investigative Site Geneve 14 Switzerland 1211
    69 Far Eastern Memorial Hospital New Taipei Taiwan 22060
    70 Taipei Veterans General Hospital Taipei Taiwan 11217
    71 Novartis Investigative Site Bangkok Thailand 10330
    72 Novartis Investigative Site Istanbul TUR Turkey 34098
    73 Novartis Investigative Site Adana Turkey
    74 Novartis Investigative Site Ankara Turkey 06490
    75 Dept. of Pediatric Metabolic Diseases Ankara Turkey 06500
    76 Novartis Investigative Site Istanbul Turkey 34093
    77 Novartis Investigative Site Izmir Turkey 35040
    78 Novartis Investigative Site Bromwich United Kingdom B71 4HJ
    79 Novartis Investigative Site Middlesex United Kingdom UB9 6JH

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT04652726
    Other Study ID Numbers:
    • CKJX839C12301
    • 2020-002757-18
    First Posted:
    Dec 3, 2020
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Heterozygous familial hypercholesterolemia (HeFH)
    LDL-cholesterol (LDL-C)
    adolescents
    pediatric
    small interfering ribonucleic acid (siRNA)
    Additional relevant MeSH terms:
    Hyperlipoproteinemia Type II
    Hypercholesterolemia

    Study Results

    No Results Posted as of Aug 24, 2022