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

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ALN-PCSSC

Standard of Care

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Research Site 201001
Research Site 231001
Research Site 227001

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ALN-PCSSC

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage Change From Day 1 to Day 90 in LDL-C

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

Secondary Outcome Measures

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C

Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9

Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a

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

Full Information

NCT ID

NCT02963311

First Posted

November 10, 2016

Last Updated

May 14, 2020

Sponsor

The Medicines Company

1. Study Identification

Unique Protocol Identification Number

NCT02963311

Brief Title

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

Acronym

ORION-2

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

December 13, 2016 (Actual)

Primary Completion Date

October 8, 2018 (Actual)

Study Completion Date

October 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Medicines Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Homozygous Familial Hypercholesterolemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ALN-PCSSC

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ALN-PCSSC

Other Intervention Name(s)

PCSK9 synthesis inhibitor

Intervention Description

ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.

Intervention Type

Drug

Intervention Name(s)

Standard of Care

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage Change From Day 1 to Day 90 in LDL-C

Description

Time Frame

Day 1, Day 90

Title

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 Measure Information:

Title

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)

Title

Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9

Time Frame

Day 1, Day 60, Day 90

Title

Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9

Time Frame

Day 1, Day 60, Day 90

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

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)

Title

Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a

Description

The reported percent change value is the per participant calculated Mean.

Time Frame

Day 1, Day 90, Day 180 (or Final Visit)

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kees Hovingh, MD, PhD

Organizational Affiliation

Department of Vascular Medicine, Academic Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Site 201001

City

Los Angeles

State/Province

California

ZIP/Postal Code

90001

Country

United States

Facility Name

Research Site 231001

City

Amsterdam

Country

Netherlands

Facility Name

Research Site 227001

City

Parktown

State/Province

Johannesburg

ZIP/Postal Code

2193

Country

South Africa

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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