Study of ISIS 304801 versus placebo Administered Subcutaneously to Patients with Partial Lipodystrophy

Phase 1

• Conditions: Partial lipodystrophy; MedDRA version: 19.0 Level: PT Classification code 10053857 Term: Partial lipodystrophy System Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2015-000493-35-BE
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-25
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 125

Inclusion Criteria

1. Clinical diagnosis of FPL plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia.
2. Diagnosis of type 2 diabetes mellitus as defined by the ADASMCD in 2015 made at least 12 weeks prior to the screening visit
3. Hypertriglyceridemia is defined as Fasting TG = 500 mg/dL (5.7 mmol/L) at Screening and qualification visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 47
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1. A diagnosis of generalized lipodystrophy
2. A diagnosis of acquired partial lipodystrophy (APL)
3. Acute pancreatitis within 4 weeks of Screening
4. History within 6 months of Screening of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack or unstable congestive heart failure requiring a change in medication
5. Major surgery within 3 months of Screening
6. Platelet count < lower limit of normal
7. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To evaluate the safety and tolerability of ISIS 304801 in patients with FPL. To further evaluate the role of serum TGs in modulating insulin resistance in FPL patients and the impact of TGs reduction on adipose tissue distribution in FPL patients ;Primary end point(s): The primary efficacy analysis will be the comparison of percent changes from Baseline to the primary analysis time point in fasting TG between ISIS 304801 300 mg once weekly group and placebo group in the Full Analysis Set (FAS);<br> Timepoint(s) of evaluation of this end point: The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments.<br> ;Main Objective: To evaluate the efficacy of ISIS 304801 (300 mg once weekly) for reduction in severity of metabolic derangement in patients with FPL with hypertriglyceridemia and uncontrolled diabetes

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): The secondary endpoints include:<br> • Change from Baseline in HbA1c<br> • Change from Baseline in liver volume and hepatic steatosis (as assessed by MRI)<br> • Absolute change from Baseline in fasting TG<br> • Proportion of patients who achieve a = 40% reduction in fasting TG<br> • Change from Baseline in fasting plasma glucose<br> • Reduction in insulin use<br> ;Timepoint(s) of evaluation of this end point: At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The value at Month 6 is defined as the average of Week 25 and Week 26 and the value at Month 12 is defined as the average of Week 51 and Week 52 fasting assessments.