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

May 14, 2020 updated by: The Medicines Company

An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Research Site 231001
  • South Africa
    • Johannesburg
      • Parktown, Johannesburg, South Africa, 2193
        • Research Site 227001
  • United States
    • California
      • Los Angeles, California, United States, 90001
        • Research Site 201001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • PCSK9 synthesis inhibitor
Drug: Standard of Care
Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Day 1, Day 90
Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C
Time Frame: Day 1, Day 180 (or Final Visit)
Day 1, Day 180 (or Final Visit)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
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
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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.
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 Lipoprotein-a
Time Frame: Day 1, Day 90, Day 180 (or Final Visit)
Day 1, Day 90, Day 180 (or Final Visit)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Medicines Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kees Hovingh, MD, PhD, Department of Vascular Medicine, Academic Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 13, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 8, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 8, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 10, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MDCO-PCS-16-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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