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A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (ORION-2)

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ClinicalTrials.gov Identifier: NCT02963311
Recruitment Status : Completed
First Posted : November 15, 2016
Results First Posted : May 18, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Description
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Brief Summary:
The purpose of this study is to assess the safety, tolerability, and efficacy of ALN-PCSSC in participants with homozygous familial hypercholesterolemia.

Condition or disease Intervention/treatment Phase
Homozygous Familial Hypercholesterolemia Drug: ALN-PCSSC Drug: Standard of Care Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
Actual Study Start Date : December 13, 2016
Actual Primary Completion Date : October 8, 2018
Actual Study Completion Date : October 8, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ALN-PCSSC
300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy.
 Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.
Other Name: PCSK9 synthesis inhibitor

Drug: Standard of Care
Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage Change From Day 1 to Day 90 in LDL-C [ Time Frame: Day 1, Day 90 ]
    Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.

  2. Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 180 (or Final Visit) ]

Secondary Outcome Measures :
  1. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  2. Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
  3. Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
  4. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  5. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  6. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  7. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  8. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  9. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  10. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  11. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  12. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  13. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  14. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  15. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1 [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  16. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  17. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
  18. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
    The reported percent change value is the per participant calculated Mean.

  19. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]

Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, ≥12 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents.
  • Stable on a low-fat diet.
  • Stable on pre-existing, lipid-lowering therapies (such as statins, cholesterolabsorption inhibitors, bile-acid sequestrants, or combinations thereof) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
  • Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L).
  • Body weight of 40 kilograms (kg) or greater at screening.

Exclusion Criteria:

  • LDL or plasma apheresis within 8 weeks prior to the screening visit, and no plan to receive it during the study because of the attendant difficulty in maintaining stable concentrations of LDL-C while receiving apheresis.
  • Use of mipomersen or lomitapide therapy within 5 months of screening.
  • Previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations
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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): NCT02963311


Locations
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United States, California
Research Site 201001
Los Angeles, California, United States, 90001
Netherlands
Research Site 231001
Amsterdam, Netherlands
South Africa
Research Site 227001
Parktown, Johannesburg, South Africa, 2193
Sponsors and Collaborators
The Medicines Company
Investigators
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Principal Investigator: Kees Hovingh, MD, PhD Department of Vascular Medicine, Academic Medical Center
  Study Documents (Full-Text)

Documents provided by The Medicines Company:
Study Protocol  [PDF] November 7, 2016
Statistical Analysis Plan  [PDF] November 14, 2018

More Information
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Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT02963311    
Other Study ID Numbers: MDCO-PCS-16-02
First Posted: November 15, 2016    Key Record Dates
Results First Posted: May 18, 2020
Last Update Posted: May 18, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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