Familial Partial Lipodystrophy (FPL)
The BROADEN Study is a randomized, placebo controlled, double blind, Phase 2/3 multicenter trial of volanesorsen (formerly ISIS-APOCIIIRx or ISIS-304801) initiated in October 2015 designed to assess the potential effects of volanesorsen on select symptoms in patients with FPL.
Volanesorsen is an investigational new drug designed to reduce the amount of apoC-III in the bloodstream. Apolipoprotein C-III (apoC-III) is a protein found in blood that functions as a key regulator of triglyceride levels. Patients with FPL have higher levels of apoC-III and triglycerides. It is thought that decreasing the amount of apoC-III may help to lower the amount of triglycerides, which may in turn help to improve insulin sensitivity and reduce select disease symptoms.
The main purpose of the clinical trial is to determine what effect volanesorsen has on triglyceride levels in patients with FPL. The study will also assess whether or not patients with FPL taking volanesorsen have an improvement in glucose control with less insulin needs, a reduction in the amount of fat surrounding the liver and reductions in other disease symptoms.
In this clinical trial, some patients will receive the drug, and some will receive a placebo. A placebo is a substance that has no drug or other active ingredient in it. Having some patients receive placebo, instead of volanesorsen, is essential to ensure the most accurate evaluation of the effects of the drug treatment. Neither the patients nor the health care workers running the study know who receives the placebo and who receives the active drug. This is called double-blinding.
The official study title is The BROADEN Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study of ISIS 304801 Administered Subcutaneously to Patients With Familial Partial Lipodystrophy.
For information about clinical trial locations, please click here.
Primary goal of the trial:
- To see what effect volanesorsen has on triglyceride levels and other metabolic derangements in people with FPL.
Who can take part?
- Adult (≥18) men or women with a diagnosis of Familial Partial Lipodystrophy, type 2 diabetes and hypertriglyceridemia
- Additional requirements, called inclusion criteria, must also be met. Click here for more details.
- Patients must also not have certain characteristics, called exclusion criteria. Click here for more details.
Main Inclusion Criteria*:
- Fasting triglyceride levels ≥ 500 mg/dL (≥ 5.7 mmol/L) at Screening and Baseline visits.
- Diagnosis of Type 2 Diabetes
- On standard-of-care anti-diabetic therapy, and
- HbA1c ≥ 7% to ≤ 10% at Screening.
- Diagnosis of FPL is based on deficiency of subcutaneous body fat in a partial fashion assessed by physical examination and low skinfold thickness in anterior thigh by caliper measurement: men (≤ 10 mm) and women (≤ 22 mm), and at least 1 of the following:
- Genetic diagnosis of familial PL (e.g., mutations in LMNA, PPAR-γ, AKT2, CIDEC, PLIN1 genes)
- Family history of FPL or family history of abnormal and similar fat distribution plus 1 Minor Criteria
- 2 Minor Criteria (In the absence of FPL-associated genetic variant or family history) and BMI< 35 kg/m2
- MINOR Criteria
- Requirement for high doses of insulin,
- Presence of acanthosis nigricans on physical examination
- Evidence/history of polycystic ovary syndrome symptoms
- History of pancreatitis associated with hypertriglyceridemia
- Evidence of fatty liver
*Additional inclusion criteria must be met. Please contact Medpace (the company that is assisting in running the clinical study) for additional inclusion criteria.
Main Exclusion Criteria*:
- A diagnosis of generalized lipodystrophy
- Acquired partial lipodystrophy
- Treatment with Metreleptin within the last 3 months prior to Screening
*Additional exclusion criteria apply. Please contact Medpace (the company that is assisting in running the clinical study) for additional exclusion criteria.
For information on clinical study sites in your area, please contact Medpace, the company that is assisting in running the clinical study, at (866) 872-2349 or email@example.com.
What happens in the trial?
- Each patient taking part in the trial will be randomly assigned to one of 2 groups:
- Intervention group – these patients will receive the volanesorsen drug by subcutaneous injection (a small needle that is injected into the tissue layer between the skin and the muscle in the upper arm, abdomen, or thigh) once weekly for 52 weeks
- Control group – these patients will receive placebo by subcutaneous injection once weekly for 52 weeks
- This is a double blind trial, which means that neither the doctors running the trial nor the patients participating will know which patients are receiving volanesorsen and which patients are receiving placebo. There is 1:1 randomization, meaning that half of the patients will receive volanesorsen and half will receive placebo.
- • Study participants will initially receive injections at their study physician’s office. After being given instructions and training, participants or their caregiver can have the option to administer injections at home, or to have injections administered by a study-assigned nurse at home. Study patients will be required to visit their physician periodically for study procedures (some examples include: blood tests for triglyceride measurements, physical exams and vital signs, and ECGs, a test for heart function) even if receiving injections at home. The study is divided into 4 periods:
- A screening and baseline period that will last for up to 6 weeks
- During this period, potential participants in the study will be tested to be sure that they have appropriate characteristics for being enrolled in the study. Some examples include: blood tests confirming high triglycerides and genetic testing for FPL.
- A dosing period that will last 52 weeks
- During this period, patients will be receiving their once weekly injections of drug or placebo, and will periodically return to the study physician’s office for follow-up evaluations.An Open Label Extension period.
Following the Week 52 visit, patients will be offered the option of continuing treatment for another 52 weeks. During this period all patients will receive volanesorsen and no one will receive placebo
- A post-treatment follow-up period that will last 13 weeks
- During the follow-up period, patients will have a number of physician visits, where blood tests and other measurements will be taken to see what effect the drug may have had during the treatment period.
What happens after the trial?
All patients who complete the 52 week dosing period of the study will be afforded the opportunity to join an open label study where all patients will receive volanesorsen and no one will receive placebo. Participation in this study is voluntary, will require a separate informed consent form, and will be offered to all participants who complete the BROADEN Study once approved by regulatory bodies and ethics committees.
Read more at ClinicalTrials.gov.
For more information on clinical study sites in your area, please contact Medpace at (866) 872-2349 or firstname.lastname@example.org.