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Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status

Withdrawn

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

AKCEA-ANGPTL3-LRX

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia

Eligibility Criteria

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

Inclusion Criteria:

Body mass index (BMI) ≤ 35 kg/m2,
Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus OR an untreated LDL-C > 500 mg/dL (13 mmol/L) or treated LDL-C ≥ 300 mg/dL (2.59 mmol/L) together with either cutaneous or tendon xanthoma before age 10 years OR familial medical history of genetically confirmed heterozygous FH in both parents OR untreated elevated LDL-C and TC > 250 mg/dL consistent with the disease,
Patients must be on stable LDL-C lowering agents or on regular apheresis

Exclusion Criteria:

Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening, or cerebrovascular accident within 24 weeks prior to Screening.
Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%

Sites / Locations

Clinical Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AKCEA-ANGPTL3-LRX Dose 1

Arm Description

Outcomes

Primary Outcome Measures

Reduction of low density lipoprotein cholesterol (LDL-C).

Percent change in LDL-C from Baseline to week 14.

Secondary Outcome Measures

Effect of ISIS 703802 on plasma angiopoietin like 3 (ANGPTL3).

Absolute and percentage change in ANGPTL3 protein from Baseline to Week 14 will be summarized.

Effect of ISIS 703802 on lipid parameters.

Absolute and percentage change from Baseline to Week 14 will be summarized.

Evaluate plasma trough levels of ISIS 703802.

Plasma trough levels of ISIS 703802 during treatment period and those during post-treatment follow up period will be descriptively summarized.

The safety of ISIS 703802 by the incidence of treatment-emergent adverse events

The safety of ISIS 703802 will be assessed by determining adverse effects.

Full Information

NCT ID

NCT03455777

First Posted

February 22, 2018

Last Updated

November 29, 2018

Sponsor

Akcea Therapeutics

Collaborators

Ionis Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03455777

Brief Title

Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Official Title

A Phase 2 Open-Label Study to Assess the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Study withdrawn due to lack of available patients meeting entry criteria

Study Start Date

April 12, 2018 (Actual)

Primary Completion Date

September 30, 2018 (Anticipated)

Study Completion Date

December 31, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Akcea Therapeutics

Collaborators

Ionis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a single center, open-label study to evaluate the efficacy of AKCEA-ANGPTL3- LRX for reduction of low density lipoprotein cholesterol (LDL-C) levels in patients with Homozygous Familial Hypercholesterolemia (HoFH).

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

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AKCEA-ANGPTL3-LRX Dose 1

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

AKCEA-ANGPTL3-LRX

Other Intervention Name(s)

ISIS 703802

Intervention Description

Single open-label cohort

Primary Outcome Measure Information:

Title

Reduction of low density lipoprotein cholesterol (LDL-C).

Description

Percent change in LDL-C from Baseline to week 14.

Time Frame

14 weeks

Secondary Outcome Measure Information:

Title

Effect of ISIS 703802 on plasma angiopoietin like 3 (ANGPTL3).

Description

Absolute and percentage change in ANGPTL3 protein from Baseline to Week 14 will be summarized.

Time Frame

7 and 14 Weeks

Title

Effect of ISIS 703802 on lipid parameters.

Description

Absolute and percentage change from Baseline to Week 14 will be summarized.

Time Frame

7 and 14 Weeks

Title

Evaluate plasma trough levels of ISIS 703802.

Description

Plasma trough levels of ISIS 703802 during treatment period and those during post-treatment follow up period will be descriptively summarized.

Time Frame

14 Weeks

Title

The safety of ISIS 703802 by the incidence of treatment-emergent adverse events

Description

The safety of ISIS 703802 will be assessed by determining adverse effects.

Time Frame

14 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Body mass index (BMI) ≤ 35 kg/m2, Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus OR an untreated LDL-C > 500 mg/dL (13 mmol/L) or treated LDL-C ≥ 300 mg/dL (2.59 mmol/L) together with either cutaneous or tendon xanthoma before age 10 years OR familial medical history of genetically confirmed heterozygous FH in both parents OR untreated elevated LDL-C and TC > 250 mg/dL consistent with the disease, Patients must be on stable LDL-C lowering agents or on regular apheresis Exclusion Criteria: Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening, or cerebrovascular accident within 24 weeks prior to Screening. Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%

Facility Information:

Facility Name

Clinical Site

City

Québec

State/Province

Quebec

ZIP/Postal Code

G1V4W2

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

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