The BROADEN Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Partial Lipodystrophy

NCT ID: NCT02527343

Last Updated: 2021-10-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-28
• Study Completion Date: 2019-11-13

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in a randomized treatment (RT) period in participants with familial partial lipodystrophy (FPL). Following the randomized treatment period, participants who did not enter the open-label extension (OLE) period went straight to the 13-week post-treatment (PT) follow-up period and participants who were entered in the OLE period continued to receive volanesorsen for another 52 weeks (Weeks 53 to 104). Following the Week 104 visit of the OLE period, participants had an option of continued dosing for up to an additional 52 weeks (Week 105 to 156). Participants who did not enter the OLE period went straight to a 13-week post-treatment follow-up period. Following the Week 104 OLE period, participants were entered a 13-week post-treatment follow-up period, if they did not choose the option for continued dosing.

Conditions

Familial Partial Lipodystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo/Volanesorsen

Randomized Period: Volanesorsen-matching placebo as SC, QW for Weeks 1-52. Participants who received volanesorsen-matching placebo in RT period and not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed.

OLE Period: Participants who received volanesorsen-matching placebo in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Weeks 105-156). Participants not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE.

Group Type: EXPERIMENTAL

volanesorsen

Intervention Type: DRUG

300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW).

Placebo

Intervention Type: DRUG

Volanesorsen-matching placebo administered SC injection.

Volanesorsen

Randomized Period: 300 mg of volanesorsen as SC, QW for Weeks 1-52. Participants who received 300 mg of volanesorsen in RT period and did not enter in OLE period went straight to 13-week PT follow-up period. Dose adjustment based on monitoring rules were allowed.

OLE Period: Participants who received volanesorsen in RT period and completed RT period, were to receive 300 mg of volanesorsen as SC QW for 52 weeks (Weeks 53-104) in OLE period. Dose adjustment based on monitoring rules were allowed. After Week 104, participants had option of continuing treatment with 300 mg of volanesorsen as SC injection for up to additional 52 weeks (Week 105-156). Participants who were not entered in option for additional 52 weeks of dosing in OLE PT period went straight to 13-week PT follow-up period after completion of first 52 weeks (Weeks 53-104) of OLE. Participants entered in OLE PT period went straight to 13-week PT follow-up period after completion of Week 156 of OLE.

Group Type: EXPERIMENTAL

volanesorsen

Intervention Type: DRUG

300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW).

Interventions

volanesorsen

300 mg of volanesorsen administered subcutaneous (SC) injection, once-weekly (QW).

Intervention Type: DRUG

Placebo

Volanesorsen-matching placebo administered SC injection.

Intervention Type: DRUG

Other Intervention Names

ISIS 304801; IONIS-APOCIIIRx

Eligibility Criteria

Inclusion Criteria

• Must give written informed consent to participate in the study (signed and dated) and any authorizations required by law.
• Clinical diagnosis of familial partial lipodystrophy (FPL) plus diagnosis of type 2 diabetes mellitus, hypertriglyceridemia, and fatty liver.
• 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 (less than or equal to [≤] 10 millimeters [mm]) and women (≤ 22 mm), and at least 1 of the following:

1. Genetic diagnosis of FPL OR

2. Family history of FPL or of similar abnormal fat distribution plus 1 Minor Criteria OR

3. In the absence of FPL-associated genetic variant or family history, 2 Minor Criteria and body mass index (BMI) less than (<) 35 kilogram per meter square (kg/m^2).

• Diabetes not well controlled on antidiabetic therapy with glycated hemoglobin (Hb) HbA1c more than or equal to (≥) 7 percentage (%) to ≤ 12% at Screening.
• Hypertriglyceridemia with fasting triglycerides (TG) levels greater than or equal to (≥) 500 milligrams per deciliter (mg/dL) (≥ 5.7 millimoles per liter [mmol/L]) at Screening and Qualification visit, or Fasting TG levels ≥ 200 (≥ 2.26 mmol/L) at both Screening and Qualification Visits for participants who meet the genetic or family history criteria.
• Presence of hepatosteatosis (fatty liver), as evidenced by a screening magnetic resonance imaging (MRI) indicating a hepatic fat fraction (HFF) ≥ 6.4%.

Exclusion Criteria

• A diagnosis of generalized lipodystrophy.
• A diagnosis of acquired partial lipodystrophy.
• Acute pancreatitis within 4 weeks of Screening.
• History within 6 months of Screening of acute or unstable cardiac condition.
• Low-density lipoprotein cholesterol (LDL-C) more than (>) 130 mg/dL on maximal tolerated statin therapy.
• Platelet count < lower limit of normal (LLN).
• Treatment with metreleptin within the last 3 months prior to Screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Akcea Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IONIS Investigative Site

Ann Arbor, Michigan, United States

IONIS Investigative Site

Rochester, Minnesota, United States

IONIS Investigative Site

St Louis, Missouri, United States

IONIS Investigative Site

Morehead City, North Carolina, United States

IONIS Investigative Site

Philadelphia, Pennsylvania, United States

IONIS Investigative Site

Dallas, Texas, United States

IONIS Investigative Site

Leuven, , Belgium

IONIS Investigative Site

Rio de Janeiro, , Brazil

IONIS Investigative Site

Halifax, Nova Scotia, Canada

IONIS Investigative Site

Münster, , Germany

IONIS Investigative Site

Amsterdam-Zuidoost, , Netherlands

IONIS Investigative Site

Moscow, , Russia

Countries

United States; Belgium; Brazil; Canada; Germany; Netherlands; Russia

References

Prohaska TA, Alexander VJ, Karwatowska-Prokopczuk E, Tami J, Xia S, Witztum JL, Tsimikas S. APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia. J Clin Lipidol. 2023 May-Jun;17(3):406-411. doi: 10.1016/j.jacl.2023.04.007. Epub 2023 Apr 27.

Reference Type: DERIVED

PMID: 37164837 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000493-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISIS 304801-CS17

Identifier Type: -

Identifier Source: org_study_id