A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (ORION-2)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02963311 |
Recruitment Status :
Completed
First Posted : November 15, 2016
Results First Posted : May 18, 2020
Last Update Posted : May 18, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Homozygous Familial Hypercholesterolemia | Drug: ALN-PCSSC Drug: Standard of Care | Phase 2 |
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 |

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. |
- 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.
- Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 180 (or Final Visit) ]
- 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) ]
- Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
- Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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.
- 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) ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

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
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 |
Principal Investigator: | Kees Hovingh, MD, PhD | Department of Vascular Medicine, Academic Medical Center |
Documents provided by The Medicines Company:
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 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Hyperlipoproteinemia Type II Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders |
Metabolic Diseases Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Hyperlipoproteinemias |