Phase 2
Completed N=4
Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Partial Lipodystrophy (FPL)
Familial Partial Lipodystrophy
Source: ClinicalTrials.gov NCT03514420 ↗
Enrolled (actual)
4
Serious AEs
75.0%
Results posted
Feb 2021
Primary outcomePrimary: Percent Change From Baseline in Fasting Triglycerides Levels at End of the Treatment (Week 27) — -59.9 percent change
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Fasting Triglycerides Levels at End of the Treatment (Week 27) |
-59.9 | — |
| SECONDARY Change From Baseline in Area Under the Curve (AUC) of Plasma Glucose as Assessed by Mixed Meal Test (MMT) at End of the Treatment |
-9815.0 | — |
| SECONDARY Change From Baseline in AUC of Serum Insulin as Assessed by MMT at End of the Treatment |
3262.0 | — |
| SECONDARY Change From Baseline in AUC of Serum C-peptide as Assessed by MMT at End of the Treatment |
-192.3 | — |
| SECONDARY Change From Baseline in AUC of Free Fatty Acid (FFA) as Assessed by MMT at End of the Treatment |
-60.0 | — |
| SECONDARY Change From Baseline in AUC of Serum Ghrelin as Assessed by MMT at End of the Treatment |
8479.5 | — |
| SECONDARY Change From Baseline in AUC of Incretin Hormone (Gastric Inhibitory Polypeptide [GIP]) as Assessed by MMT at End of the Treatment |
-1694.7 | — |
| SECONDARY Change From Baseline in AUC of Incretin Hormone (Glucagon-like Peptide -1 [GLP-1]) as Assessed by MMT at End of the Treatment |
1677.3 | — |
| SECONDARY Change From Baseline in AUC of Peptide Tyrosine Tyrosine (PYY) as Assessed by MMT at End of the Treatment |
6549.0 | — |
| SECONDARY Change From Baseline in HDL-C at End of the Treatment |
2.1 | — |
| SECONDARY Change From Baseline in LDL-C at End of the Treatment |
24.0 | — |
| SECONDARY Change From Baseline in Total Cholesterol (TC) at End of the Treatment |
-42.3 | — |
| SECONDARY Change From Baseline in VLDL-C at End of the Treatment |
-32.0 | — |
| SECONDARY Change From Baseline in Non-HDL-C at End of the Treatment |
-44.4 | — |
| SECONDARY Change From Baseline in ApoB at End of the Treatment |
1.25 | — |
| SECONDARY Change From Baseline in ApoB-48 at End of the Treatment |
-3.601 | — |
| SECONDARY Change From Baseline in Apolipoprotein B 100 (ApoB-100) at End of the Treatment |
4.433 | — |
| SECONDARY Change From Baseline in ApoA-1 at End of the Treatment |
-20.8 | — |
| SECONDARY Change From Baseline in ApoC-III at End of the Treatment |
-13.555 | — |
| SECONDARY Change From Baseline in ApoC-III: Chylomicron at End of the Treatment |
— | — |
| SECONDARY Change From Baseline in ApoC-III: VLDL at End of the Treatment |
— | — |
| SECONDARY Change From Baseline in ApoC-III: LDL at End of the Treatment |
-2.110 | — |
| SECONDARY Change From Baseline in ApoC-III: HDL at End of the Treatment |
-9.904 | — |
| SECONDARY Change From Baseline in Lipoprotein a (Lp[a]) at End of the Treatment |
8.4 | — |
| SECONDARY Change From Baseline in Free Fatty Acid (FFA) at End of the Treatment |
-0.5779 | — |
| SECONDARY Change From Baseline in Glycerol Levels at End of the Treatment |
-8.0 | — |
| SECONDARY Change From Baseline in Lipoprotein Particle Size at End of the Treatment |
0.1; 0.2; -8.7 | — |
| SECONDARY Change From Baseline in Hemoglobin A1c (HbA1c) at End of the Treatment |
-0.23 | — |
| SECONDARY Change From Baseline in Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) |
— | — |
| SECONDARY Change From Baseline in Adiponectin at End of the Treatment |
0.08 | — |
| SECONDARY Change From Baseline in and Leptin at End of the Treatment |
-0.19 | — |
| SECONDARY Change From Baseline in Hepatic Fat Fraction (HFF) as Assessed by Magnetic Resonance Imaging (MRI) at End of the Treatment |
-1.1400 | — |
| SECONDARY Changes From Baseline in Body Fat Distribution for Various Areas in the Body as Measured by Skinfold Thickness at End of the Treatment |
1.6; -2.1 | — |
| SECONDARY 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 |
11.3; 603.8; 273.3; 875.0; 16.5; 436.8 | — |
| SECONDARY 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 |
0.0 | — |
| SECONDARY Change From Baseline in Visceral Adipose Tissue (VAT) as Measured by Magnetic Resonance Imaging (MRI) at End of the Treatment |
— | — |
| SECONDARY Change From Baseline in Subcutaneous Adipose Tissue (SAT) as MRI at End of the Treatment |
— | — |
| SECONDARY Change From Baseline in Body Weight at End of the Treatment |
-1.05 | — |
| SECONDARY Change From Baseline in Waist Circumference at End of the Treatment |
-1.88 | — |
| SECONDARY Change From Baseline in Waist/Hip Ratio at End of the Treatment |
— | — |
| SECONDARY Change From Baseline in Quality of Life (QoL) |
1; 1; 2; 0; 0; 4 | — |
| SECONDARY Change From Baseline in Pain Score at End of the Treatment |
-3.8 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
4 | — |
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.
Data sourced from ClinicalTrials.gov (NCT03514420). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.