Familial Chylomicronemia Syndrome MedDRA version: 20.0 Level: PT Classification code 10020606 Term: Hyperchylomicronaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: WAYLIVRA®
Product Name: Volanesorsen
Product Code: ISIS 304801
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Volanesorsen
Current Sponsor code: ISIS 304801
Concentration
Sponsors
Akcea Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort 1 Inclusion Criteria: 1. Age = 12 years and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Body weight upper limit of normal (ULN), unless prior diagnosis and documentation of Gilbert’s syndrome in which case total bilirubin must be = 3 mg/dL • Alanine Aminotransferase (ALT) > 2.0 x ULN • Aspartate Aminotransferase (AST) > 2.0 x ULN b. Renal: • Persistently positive proteinuria: urine protein/creatinine ratio (UPCR) > 0.2 mg/mg on 2 tests separated by at least 7 days • Persistently positive hematuria: urine microscopy showing > 5 red blood cells per high power field on 2 tests separated by at least 7 days • Estimated GFR (eGFR) 130 mg/dL at screening d. Platelet count < 140,000/mm3 e. Any other laboratory abnormalities which, in the opinion of the Investigator or the Sponsor, would make the patient unsuitable for inclusion 4. History of chronic kidney disease 5. Uncontrolled thyroid disease 6. Has uncontrolled hypertension (average clinic measured SBP and/or DBP =95th percentile on the basis of age, sex, and height percentiles)** **See Appendix E Blood Pressure Tables for Boys and Girls by Age and Height Percentile 7. History of bleeding diathesis or coagulopathy or clinically-significant abnormality in coagulation parameters at screening 8. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 9. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B 10. History of malignancy 11. History of alcoholism or drug/chemical abuse within 1 year of screening 12. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer 13. Unwilling or unable to comply with lifestyle requirements 14. History of major psychosis or major depressive disorder 15. Use of any of the following: a. Statins, omega-3 fatty acids (prescription and over-the-counter [OTC]), or fibrates unless on a stable dose for at least 3 months prior to screening and dose and regimen expected to remain constant during the Treatment Period. Patients taking OTC omega-3 fatty acids should make every effort to remain on the same brand throughout the study b. Nicotinic acid or derivatives of nicotinic acid within 4 weeks prior to screening c. Systemic corticosteroids or anabolic steroids within 6 weeks prior to screening d. Treatment with oral anticoagulant medications e. Estrogens or progestins (including birth control pills) unless on a stable dose for at least 6 weeks prior to screening and dose and regimen expected to remain constant during the Treatment Period f. Plasma apheresis within 4 weeks prior to screening or planned during the study g. Prior exposure to volanesorsen within the last 6 months h. Any other medication unless stable at least 4 weeks prior to screening. Occasional or intermittent use of over-the-counter medications will be allowed at Investigator’s discretion 16. Known hypersensitivity to any of the excipients of volanesorsen 17. In the opinion of the Investigator, inability to comply with the protocol 18. Have any other conditions, including history of significant cardiac disease which, in the opinion of the Investigator or the Sponsor wo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of volanesorsen sodium (ISIS 304801) administered by subcutaneous (SC) injection to adolescent and pediatric patients with FCS.;Secondary Objective: To evaluate the safety, pharmacodynamic profile, and pharmacokinetic profile of volanesorsen sodium (ISIS 304801) administered by subcutaneous (SC) injection to adolescent and pediatric patients with FCS.;Primary end point(s): To evaluate the efficacy of volanesorsen administered SC to adolescent and pediatric patients with Familial Chylomicronemia Syndrome (FCS) by assessing the following: • Percent change in fasting triglycerides from Baseline to the primary analysis time point at Week 13.;Timepoint(s) of evaluation of this end point: Baseline, Week 13 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To further evaluate the efficacy, safety and PK/PD profile of volanesorsen administered SC to adolescent and pediatric patients with Familial Chylomicronemia Syndrome (FCS) by assessing the following: • Percent change from baseline in fasting TG at Weeks 25, 53, 77, and 105 • Change from baseline in fasting TG at Weeks 13, 25, 53, 77, and 105 • Proportion of patients who achieve fasting TG < 750 mg/dL overall and at Weeks 13, 25, 53, 77, and 105 • Proportion of patients who achieve fasting TG < 500 mg/dL overall and at Weeks 13, 25, 53, 77, and 105 • Proportion of patients who achieve = 40% fasting TG reduction from baseline overall and at Weeks 13, 25, 53, 77, and 105 • Change and percent change from baseline in other fasting lipid measurements at Weeks 13, 25, 53, 77, and 105 including: total apolipoprotein C-III (apoC-III), total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein-cholesterol (HDL-C), apoB, apoA-1, very-low-density lipoprotein-cholesterol (VLDL-C), and low-density lipoprotein-cholesterol (LDLC) • Comparison of adjudicated acute pancreatitis event rate and patient reported abdominal pain prior to first dose of Study Drug (including events based on medical chart review) vs. adjudicated pancreatitis events and patient reported abdominal pain on treatment at Week 25 and Week 53 • Change from baseline in hepatosplenomegaly as assessed by MRI at Week 53 and optional Week 105 • Change in Quality of Life from baseline at Weeks 13, 25, 53, 77, and 105;Timepoint(s) of evaluation of this end point: Baseline, 13, 25, 53, 77, and 105 | — |
Countries
Australia, Austria, France, Germany, Italy, Netherlands, Poland, Serbia, South Africa, Spain, Switzerland, United Kingdom
Contacts
Public ContactAkcea Clinical Trials
Akcea Therapeutics, Inc.
Outcome results
None listed