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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04652726




Registration number
NCT04652726
Ethics application status
Date submitted
2/12/2020
Date registered
3/12/2020
Date last updated
23/08/2023

Titles & IDs
Public title
Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Heterozygous Familial Hypercholesterolemia
Scientific 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)
Secondary ID [1] 0 0
2020-002757-18
Secondary ID [2] 0 0
CKJX839C12301
Universal Trial Number (UTN)
Trial acronym
ORION-16
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Familial Hypercholesterolemia - Heterozygous 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inclisiran
Treatment: Drugs - Placebo

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)

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)


Treatment: Drugs: Inclisiran
Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL solution for subcutaneous injection

Treatment: Drugs: Placebo
Sterile normal saline (0.9% sodium chloride in water for subcutaneous injection)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330
Timepoint [1] 0 0
Baseline and Day 330
Secondary outcome [1] 0 0
Time-adjusted % change in LDL-C from baseline after Day 90 and up to Day 330
Timepoint [1] 0 0
Baseline, after Day 90 up to Day 330
Secondary outcome [2] 0 0
Absolute change in LDL-C from baseline to Day 330
Timepoint [2] 0 0
Baseline and Day 330
Secondary outcome [3] 0 0
% 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
Timepoint [3] 0 0
Baseline and Day 330
Secondary outcome [4] 0 0
% change and absolute change in LDL-C from baseline up to Day 720
Timepoint [4] 0 0
Baseline, up to Day 720
Secondary outcome [5] 0 0
% change and absolute change in other lipoproteins and lipid parameters from baseline up to Day 720
Timepoint [5] 0 0
Baseline, up to Day 720
Secondary outcome [6] 0 0
% change and absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline up to Day 720
Timepoint [6] 0 0
Baseline, up to Day 720

Eligibility
Key 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
Minimum age
12 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/12/2024
Actual
Sample size
Target
Accrual to date
Final
141
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
Argentina
State/province [7] 0 0
Formosa
Country [8] 0 0
Brazil
State/province [8] 0 0
Ceara
Country [9] 0 0
Brazil
State/province [9] 0 0
RS
Country [10] 0 0
Brazil
State/province [10] 0 0
SP
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha 2
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 5
Country [14] 0 0
France
State/province [14] 0 0
Besancon Cedex
Country [15] 0 0
France
State/province [15] 0 0
Bron Cedex
Country [16] 0 0
France
State/province [16] 0 0
Toulouse Cedex
Country [17] 0 0
Germany
State/province [17] 0 0
Baden-Wuerttemberg
Country [18] 0 0
Germany
State/province [18] 0 0
Frankfurt
Country [19] 0 0
Germany
State/province [19] 0 0
Freiburg
Country [20] 0 0
Greece
State/province [20] 0 0
GR
Country [21] 0 0
Greece
State/province [21] 0 0
Athens
Country [22] 0 0
Hungary
State/province [22] 0 0
Pecs
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Ramat Gan
Country [25] 0 0
Italy
State/province [25] 0 0
MI
Country [26] 0 0
Italy
State/province [26] 0 0
MO
Country [27] 0 0
Italy
State/province [27] 0 0
RM
Country [28] 0 0
Jordan
State/province [28] 0 0
Irbid
Country [29] 0 0
Lebanon
State/province [29] 0 0
Ashrafieh
Country [30] 0 0
Malaysia
State/province [30] 0 0
Selangor Darul Ehsan
Country [31] 0 0
Netherlands
State/province [31] 0 0
Zuid Holland
Country [32] 0 0
Netherlands
State/province [32] 0 0
Amsterdam
Country [33] 0 0
Norway
State/province [33] 0 0
Oslo
Country [34] 0 0
Poland
State/province [34] 0 0
Gdansk
Country [35] 0 0
Poland
State/province [35] 0 0
Lodz
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Kemerovo
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Moscow
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Novosibirsk
Country [39] 0 0
Slovakia
State/province [39] 0 0
Poprad
Country [40] 0 0
Slovenia
State/province [40] 0 0
Ljubljana
Country [41] 0 0
South Africa
State/province [41] 0 0
Free State
Country [42] 0 0
South Africa
State/province [42] 0 0
Gauteng
Country [43] 0 0
South Africa
State/province [43] 0 0
Western Cape
Country [44] 0 0
South Africa
State/province [44] 0 0
Cape Town
Country [45] 0 0
Spain
State/province [45] 0 0
Andalucia
Country [46] 0 0
Spain
State/province [46] 0 0
Asturias
Country [47] 0 0
Spain
State/province [47] 0 0
Navarra
Country [48] 0 0
Spain
State/province [48] 0 0
A Coruna
Country [49] 0 0
Switzerland
State/province [49] 0 0
Geneve 14
Country [50] 0 0
Taiwan
State/province [50] 0 0
New Taipei
Country [51] 0 0
Taiwan
State/province [51] 0 0
Taipei
Country [52] 0 0
Turkey
State/province [52] 0 0
TUR
Country [53] 0 0
Turkey
State/province [53] 0 0
Adana
Country [54] 0 0
Turkey
State/province [54] 0 0
Ankara
Country [55] 0 0
Turkey
State/province [55] 0 0
Izmir
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Middlesex

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04652726
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04652726