Homozygous Familial HypercholesterolemiaPhase 2ORION-2NCT02963311

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

A Phase 2 study testing ALN-PCSSC in people with Homozygous Familial Hypercholesterolemia, run by The Medicines Company at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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

Who is it for?: Ages 12 years and older
Conditions the study is for: Homozygous Familial Hypercholesterolemia
What is being tested?: ALN-PCSSC
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 9 participants
Where: 3 sitesin 3 countries
Study dates: 13 Dec 2016to 8 Oct 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

United States1 site

Research Site 201001
Los Angeles, California, 90001

Other trials in United States

Netherlands1 site

Research Site 231001
Amsterdam

Other trials in Netherlands

South Africa1 site

Research Site 227001
Parktown, Johannesburg, 2193

Other trials in South Africa

About this study

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)

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

Conditions: Homozygous Familial Hypercholesterolemia
Being tested: ALN-PCSSC, Standard of Care
Medical subject headings: Homozygous Familial Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ALN-PCSSCDrug
Also called PCSK9 synthesis inhibitor
ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.
Standard of CareDrug
Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

Study groups in NCT02963311
Study group	Role	What they receive
ALN-PCSSC	Experimental	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. Receives: Drug: ALN-PCSSC; Drug: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Day 1, Day 90
Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C
Measured: Day 1, Day 180 (or Final Visit)

Secondary outcomes (19)

Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C
Measured: Day 1, Day 90, Day 180 (or Final Visit)
Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9
Measured: Day 1, Day 60, Day 90
Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9
Measured: Day 1, Day 60, Day 90
Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
The reported percent change value is the per participant calculated Mean.
Measured: 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
Measured: Day 1, Day 90, Day 180 (or Final Visit)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Dec 20168 Oct 2018

First posted15 Nov 2016 (estimated)
Study start13 Dec 2016
Primary completion8 Oct 2018
Study completion8 Oct 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 9 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02963311
Sponsor's protocol ID: MDCO-PCS-16-02
Acronym: ORION-2
Status last verified: May 2020
First submitted: 10 Nov 2016
Last updated: 18 May 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
RecruitingPhase 3
Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
Recruiting
The ORIGIN-FH Study
Heterozygous Familial Hypercholesterolemia (HeFH), Homozygous Familial Hypercholesterolemia (HoFH)
RecruitingPhase 3
Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
Heterozygous or Homozygous Familial Hypercholesterolemia
RecruitingPhase 1
A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias
Cardiovascular, Metabolic Disease

All Homozygous Familial Hypercholesterolemia trials

Study at a glance

From the registry record, last updated by the sponsor on 18 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02963311
Acronym / sponsor ID: ORION-2 / MDCO-PCS-16-02
Conditions: Homozygous Familial Hypercholesterolemia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 9 participants (actual)
Lead sponsor: The Medicines CompanyIndustry (pharma, biotech, devices)
Study start: 13 Dec 2016 (actual)
Primary completion: 8 Oct 2018 (actual)
Study completion: 8 Oct 2018 (actual)
First posted: 15 Nov 2016 (estimated)
Results: Posted 18 May 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ALN-PCSSC	Experimental	Drug: ALN-PCSSC, Drug: Standard of Care300 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.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ALN-PCSSCAlso: PCSK9 synthesis inhibitorALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.	Drug	ALN-PCSSC
Standard of CareIncluded maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.	Drug	ALN-PCSSC

Primary outcome

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)

19 secondary outcomes

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)
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)

Results and safety

Results posted to the registry on 18 May 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Inclisiran	9	4

Primary outcome: Percentage Change From Day 1 to Day 90 in LDL-C

Time frame: Day 1, Day 90. Mean (95% Confidence Interval). Unit: percent change

Measure	Inclisiran n = 4
Value	-12.26 (-43.75 to 19.24)

Primary outcome: Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C

Time frame: Day 1, Day 180 (or Final Visit). Mean (95% Confidence Interval). Unit: percent change

Measure	Inclisiran n = 4
Value	-20.96 (-49.97 to 8.05)

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: 18 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Inclisiran	1 of 4 (25%)	3 of 4 (75%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Homozygous Familial Hypercholesterolemia

Active, not recruitingObservational study
Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia (HoFH), Major Adverse Cardiovascular Events (MACE)
RecruitingPhase 3
Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
Recruiting
The ORIGIN-FH Study
Heterozygous Familial Hypercholesterolemia (HeFH), Homozygous Familial Hypercholesterolemia (HoFH)
RecruitingPhase 3
Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
Heterozygous or Homozygous Familial Hypercholesterolemia
RecruitingPhase 1
A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias
Cardiovascular, Metabolic Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kees Hovingh, MD, PhD principal investigator

Department of Vascular Medicine, Academic Medical Center

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ALN-PCSSC in people with Homozygous Familial Hypercholesterolemia, run by The Medicines Company at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Netherlands, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change From Day 1 to Day 90 in LDL-C (time frame: Day 1, Day 90). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02963311.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2020.