Clinical trial NCT03514420: Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Partial Lipodystrophy (FPL)
Official title: An Open-label Phase 2 Study of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Subjects With Familial Partial Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Familial Partial Lipodystrophy
Keywords: Lipodystrophy
Lipodystrophy, Familial Partial
Lipid Metabolism Disorders
Dyslipidemias
Kobberling-Dunnigan syndrome (type 1 and 2)
Lipoatrophic Diabetes
Lead sponsor: Akcea Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2018-05-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in Fasting Triglycerides Levels at End of the Treatment (Week 27)
timeFrame: Baseline and End of the Treatment (Week 27)
Secondary outcomes:
measure: Change From Baseline in Area Under the Curve (AUC) of Plasma Glucose as Assessed by Mixed Meal Test (MMT) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Serum Insulin as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Serum C-peptide as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Free Fatty Acid (FFA) as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Serum Ghrelin as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Incretin Hormone (Gastric Inhibitory Polypeptide [GIP]) as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Incretin Hormone (Glucagon-like Peptide -1 [GLP-1]) as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in AUC of Peptide Tyrosine Tyrosine (PYY) as Assessed by MMT at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in HDL-C at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in LDL-C at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Total Cholesterol (TC) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in VLDL-C at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Non-HDL-C at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoB at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoB-48 at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Apolipoprotein B 100 (ApoB-100) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoA-1 at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoC-III at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoC-III: Chylomicron at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoC-III: VLDL at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoC-III: LDL at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in ApoC-III: HDL at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Lipoprotein a (Lp[a]) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Free Fatty Acid (FFA) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Glycerol Levels at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Lipoprotein Particle Size at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR)
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Adiponectin at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in and Leptin at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Hepatic Fat Fraction (HFF) as Assessed by Magnetic Resonance Imaging (MRI) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Changes From Baseline in Body Fat Distribution for Various Areas in the Body as Measured by Skinfold Thickness at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: 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
timeFrame: Baseline and End of the Treatment (Week 27)
measure: 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
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Visceral Adipose Tissue (VAT) as Measured by Magnetic Resonance Imaging (MRI) at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Subcutaneous Adipose Tissue (SAT) as MRI at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Body Weight at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Waist Circumference at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Waist/Hip Ratio at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Quality of Life (QoL)
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Change From Baseline in Pain Score at End of the Treatment
timeFrame: Baseline and End of the Treatment (Week 27)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From signing of informed consent to end of follow up period (Up to week 40)
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: Clinical Site
state: Michigan
Study officials:
References: