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

• Register: EUCTR
• Last refreshed on: 7 December 2020
• Main ID: EUCTR2015-000493-35-DE
• Date of registration: 14/08/2015
• Prospective Registration: Yes
• Primary sponsor: Akcea Therapeutics, Inc.
• Public title: Study of ISIS 304801 versus placebo Administered Subcutaneously to Patients with Partial Lipodystrophy
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, with an Open Label Extension, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients with Familial Partial Lipodystrophy - The BROADEN Study
• Date of first enrolment: 17/02/2016
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000493-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Canada, France, Germany, Greece, Israel, Italy, Netherlands, Portugal, Russian Federation, Spain, Turkey, United Kingdom, United States

Contacts

• Affiliation: Akcea Therapeutics, Inc.

• Affiliation: Akcea Therapeutics, Inc.

Key inclusion & exclusion criteria

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 International Diabetes Federation guidelines made at least 6 months 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 57
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
7. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Partial lipodystrophy
MedDRA version: 20.0 Level: PT Classification code 10053857 Term: Partial lipodystrophy System Organ Class: 10040785 - Skin and subcutaneous tissue disorders

Intervention(s)

Product Name: VOLANESORSEN SODIUM, ApoC-III Antisense Oligonucleotide
Product Code: ISIS 304801
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 304801
CAS Number: 915430-78-3
Current Sponsor code: ISIS 304801
Other descriptive name: ISIS 304801
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

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

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)

Secondary Outcome(s)

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.

Secondary end point(s): The secondary endpoints include:
• Change from baseline in HbA1c

• Change from Baseline in hepatic steatosis (as
assessed by hepatic fat fraction using MRI)

• A composite endpoint at Month 6 for percent of patients who achieve a = 40% reduction in fasting TG b =30% of hepatic fat fraction percent

• Change in patient reported outcomes: Disease burden score, patient reported pain, Patient reported hunger, QoL

Secondary ID(s)

ISIS-304801-CS17

Source(s) of Monetary Support

Akcea Therapeutics

Ethics review

Status: Approved
Approval date: 17/02/2016
Contact: