- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03514420
Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Partial Lipodystrophy (FPL)
January 27, 2021 updated by: Akcea Therapeutics
An Open-label Phase 2 Study of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Subjects With Familial Partial Lipodystrophy
This is a single-center, open-label study to evaluate the efficacy of AKCEA-ANGPTL3-LRx for reduction of fasting triglycerides in participants with familial partial lipodystrophy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
4
Phase
- 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
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Michigan
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Ann Arbor, Michigan, United States, 48105
- Clinical Site
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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
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Must give written informed consent to participate in the study.
- Clinical diagnosis of familial partial lipodystrophy plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia.
- Diagnosis of diabetes mellitus, made at least 6 months prior to the Screening with hemoglobin A1c (HbA1c) ≥ 7% to ≤ 12% at Screening and on anti-diabetic therapy as defined in study protocol.
- Hypertriglyceridemia as defined by fasting triglycerides (TG) levels ≥ 500 milligrams per deciliter (mg/dL) at both Screening and Qualification visits. Participants with the clinical diagnosis of FPL and with fasting TG levels ≥ 200 (≥ 2.26 millimoles per liter [mmol/L]) to < 500 mg/dL (≥ 5.7 mmol/L) who meet the genetic or family history criteria for study inclusion may be further screened and enrolled in the study.
- Presence of hepatosteatosis (fatty liver), as evidenced by a Screening magnetic resonance imaging (MRI) indicating a hepatic fat fraction (HFF) ≥ 6.4%.
Key Exclusion Criteria:
- Diagnosis of generalized lipodystrophy.
- Diagnosis of acquired partial lipodystrophy (APL).
- Acute pancreatitis within 4 weeks of Screening.
- Acute coronary syndrome within 6 months of Screening.
- Major surgery within 3 months of Screening.
- Have any other conditions in the opinion of the investigator which could interfere with the participant participating in or completing the study.
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 |
Intervention / Treatment |
---|---|
Experimental: AKCEA-ANGPTL3-LRx 20 mg
Participants received AKCEA-ANGPTL3-LRx 20 milligrams (mg) administered every week for 26 weeks by subcutaneous (SC) injection.
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AKCEA-ANGPTL3-LRx solution for SC injection.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Fasting Triglycerides Levels at End of the Treatment (Week 27)
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Area Under the Curve (AUC) of Plasma Glucose as Assessed by Mixed Meal Test (MMT) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the area under the curve (AUC) of Plasma Glucose was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Serum Insulin as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of Serum Insulin was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Serum C-peptide as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of Serum C-peptide was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Free Fatty Acid (FFA) as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of FFA was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Serum Ghrelin as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of Serum Ghrelin was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Incretin Hormone (Gastric Inhibitory Polypeptide [GIP]) as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of Incretin Hormone: GIP was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Incretin Hormone (Glucagon-like Peptide -1 [GLP-1]) as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of Incretin Hormone: GLP-1 was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in AUC of Peptide Tyrosine Tyrosine (PYY) as Assessed by MMT at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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Change from Baseline to Week 27 in the AUC of PYY was assessed.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in HDL-C at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in LDL-C at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
LDL-C calculated using ultracentrifugation method.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Total Cholesterol (TC) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in VLDL-C at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
VLDL-C was calculated using direct test method.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Non-HDL-C at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoB at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoB-48 at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Apolipoprotein B 100 (ApoB-100) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoA-1 at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoC-III at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoC-III: Chylomicron at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoC-III: VLDL at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoC-III: LDL at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in ApoC-III: HDL at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Lipoprotein a (Lp[a]) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Free Fatty Acid (FFA) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Glycerol Levels at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Lipoprotein Particle Size at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Day 1 pre-dose fasting assessment.
Lipoprotein Particle size included: HDL size, LDL size and VLDL size.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Hemoglobin A1c (HbA1c) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the last non-missing assessment prior to the first dose of study drug.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR)
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the average of Day 1 pre-dose fasting assessment and the last fasting measurement prior to Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Adiponectin at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Day 1 pre-dose fasting assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in and Leptin at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Day 1 pre-dose fasting assessment
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Hepatic Fat Fraction (HFF) as Assessed by Magnetic Resonance Imaging (MRI) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the last non-missing assessment prior to the first dose of study drug.
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Baseline and End of the Treatment (Week 27)
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Changes From Baseline in Body Fat Distribution for Various Areas in the Body as Measured by Skinfold Thickness at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the last assessment prior to the first dose of study drug.
Change in body fat distribution was measured as right anterior thigh skinfold thickness and right tricep skinfold thickness by Skinfold Thickness.
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Baseline and End of the Treatment (Week 27)
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Changes From Baseline in Body Fat Distribution for Various Areas in the Body as Measured by Dual-Energy X-ray Absorptiometry (DEXA) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Screening assessment.
Change in body fat distribution (arm bone mass, arm fat mass, arm lean mass, arm total mass, leg bone mass, leg fat mass, leg lean mass, leg total mass, total bone mass, total fat mass, total lean mass, total total mass , trunk bone mass, trunk fat mass, trunk lean mass and trunk total mass) was measures obtained from DEXA.
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Baseline and End of the Treatment (Week 27)
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Changes From Baseline in Body Fat Distribution for Total Bone Mineral Density in the Body as Measured by Dual-Energy X-ray Absorptiometry (DEXA) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as Screening assessment.
Change in body fat distribution for total Bone mineral density was measures obtained from DEXA.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Visceral Adipose Tissue (VAT) as Measured by Magnetic Resonance Imaging (MRI) at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the last assessment prior to the first dose of study drug.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Subcutaneous Adipose Tissue (SAT) as MRI at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the last assessment prior to the first dose of study drug.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Body Weight at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Day 1 pre-dose assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Waist Circumference at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the Screening assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Waist/Hip Ratio at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as screening assessment.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Quality of Life (QoL)
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as the screening assessment.
Quality of life measures the severity of fatigue, severity of trouble thinking or remembering and severity of waking up tired in participants, on a scale ranging from 0 to 3, where, 0= No problem, 1= Mild, 2= Moderate and 3= severe.
Higher scores indicates more severity or more impact on quality of life.
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Baseline and End of the Treatment (Week 27)
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Change From Baseline in Pain Score at End of the Treatment
Time Frame: Baseline and End of the Treatment (Week 27)
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The baseline was defined as a Screening assessment.
Pain score is used to determine disease activity in participants, on a scale ranging from 0 to 5 where 0= never, 1= hardly noticed, 2= slightly, 3= moderately, 4= strongly, and 5= very strongly where higher scores indicated higher degree of pain.
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Baseline and End of the Treatment (Week 27)
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Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: From signing of informed consent to end of follow up period (Up to week 40)
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An adverse event (AE) is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product.
"A treatment-emergent adverse event (TEAE) is defined as any AE starting on or after the first dose of the study drug
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From signing of informed consent to end of follow up period (Up to week 40)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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)
June 15, 2018
Primary Completion (Actual)
July 30, 2019
Study Completion (Actual)
August 21, 2019
Study Registration Dates
First Submitted
April 21, 2018
First Submitted That Met QC Criteria
April 21, 2018
First Posted (Actual)
May 2, 2018
Study Record Updates
Last Update Posted (Actual)
February 16, 2021
Last Update Submitted That Met QC Criteria
January 27, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ISIS 703802-CS5
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.
Clinical Trials on Familial Partial Lipodystrophy
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University Hospital, LilleRecruitingFamilial Partial Lipodystrophy Type 2France
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Akcea TherapeuticsIonis Pharmaceuticals, Inc.TerminatedFamilial Partial LipodystrophyUnited States, Netherlands, Belgium, Brazil, Canada, Germany, Russian Federation
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Mayo ClinicCompleted
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National Institute of Diabetes and Digestive and...RecruitingLipodystrophyUnited States
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University of MichiganAvailable
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Abhimanyu GargCompletedFamilial Partial LipodystrophyUnited States
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University of MichiganCompletedNAFLD | Nonalcoholic Steatohepatitis | Familial Partial LipodystrophyUnited States
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Elif OralCompletedFatty Liver | Hypertriglyceridemia | NASH - Nonalcoholic Steatohepatitis | Familial Partial LipodystrophyUnited States
Clinical Trials on AKCEA-ANGPTL3-LRx
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Ionis Pharmaceuticals, Inc.RecruitingHereditary Transthyretin-Mediated Amyloid PolyneuropathyUnited States, Italy, Portugal, Spain, Taiwan, Sweden, Canada, Brazil, France, New Zealand, Argentina, Cyprus, Australia, Turkey
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Ionis Pharmaceuticals, Inc.Active, not recruitingTransthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)United States, Australia, Spain, Canada, Germany, Japan, Italy, Israel, Argentina, France, Portugal, Austria, Brazil, Greece, United Kingdom, Czechia, Sweden, Belgium, Denmark, Poland, Puerto Rico
-
Ionis Pharmaceuticals, Inc.Active, not recruitingFamilial Chylomicronemia SyndromeSpain, United Kingdom, France, Canada, United States, Italy, Netherlands, Norway, Portugal, Slovakia, Sweden
-
Ionis Pharmaceuticals, Inc.Completed
-
Ionis Pharmaceuticals, Inc.RecruitingCardiovascular Diseases | Atherosclerosis | HypertriglyceridemiaUnited States, Spain, Netherlands, Canada, Poland, Denmark, Italy, Hungary, France, Portugal, Norway, Bulgaria, Czechia, Slovakia
-
Ionis Pharmaceuticals, Inc.RecruitingSevere HypertriglyceridemiaUnited States, Germany, Israel, Spain, Netherlands, Australia, Hungary, Sweden, Denmark, Canada, France, Italy, Turkey, Finland, Bulgaria, Czechia, New Zealand, Norway, Poland, Portugal, Slovakia, South Africa, United Kingdom
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Ionis Pharmaceuticals, Inc.RecruitingSevere HypertriglyceridemiaUnited States, South Africa, Spain, Israel, Australia, Sweden, Canada, Denmark, Hungary, Netherlands, Bulgaria, Czechia, Italy, France, Norway, New Zealand, Slovakia, Poland