Clinical trial NCT01589237: Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
Official title: An Open Label, 52-week, Safety and Tolerability Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Familial Chylomicronemia Syndrome (FCS) (HLP Type I)
Keywords: Familial Chylomicronemia Syndrome (FCS) (HLP type I)
LCQ908
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-01
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was to determine long-term safety and tolerability, and continued efficacy in lowering triglycerides of LCQ908 in subjects with Familial Chylomicronemia Syndrome (FCS) (HLP type I).

Detailed description: This study was an 52 weeks open label extension starting at the lowest treatment dose used in CLCQ908B2302/NCT01514461 (i.e., 10 mg) with optional up-titrations, to evaluate the overall long-term safety and tolerability of LCQ908 in patients with Familial Chylomicronemia Syndrome, who either discontinued from the CLCQ908B2302/NCT01514461 study (due to tolerability issues) or completed the CLCQ908B2302/NCT01514461 study after 52 weeks. In addition, patients who had previously completed study CLCQ908A2212/NCT01146522 were eligible to participate.

Following Protocol amendment 2, the original 52 week duration of this study (CLCQ908B2305) became Part A of LCQ908B2305 and a 78 week extension became Part B. However, following Protocol amendment 3, Part B was ended at the same time as the last patient of Part A completed 52 weeks. The reason for termination of Part B was the findings from the December 2014 interim analysis which suggested that the size of benefit that was anticipated from continued participation of patients in the 18 month extension trial (Part B) no longer supported trial extension beyond Part A.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Subjects that either discontinue prematurely or complete the CLCQ908B2302 study after 52 weeks or FCS subjects who have previously completed study CLCQ908A2212.

Exclusion Criteria:

1. Subjects discontinued from the CLCQ908B2302 study for serious, potentially study drug related adverse events.
2. Subjects from the CLCQ908B2302 study who have developed any other contraindication to participation (for example, renal failure)
3. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
5. Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%.
6. Treatment with fish oil preparations within 4 weeks prior to randomization.
7. Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization.
8. Treatment with fibrates within 8 weeks prior to randomization. Washout may occur following screening if required.
9. Glybera \[alipogene tiparvovec (AAV1-LPLS447X )\] gene therapy exposure within the two years prior to screening.
10. eGFR \<45 ml/min/1.73m2 or history of chronic renal disease.

Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number of Patients With Any Adverse Events, Serious Adverse Events and Death
timeFrame: 52 weeks
Secondary outcomes:
measure: Changes From Baseline in Triglyceride Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Cholesterol Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in HDL and Non HDL Cholesterol Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Glycerol Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Free Fatty Acid Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Apolipoprotein A1 Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Apolipoprotein B-48 Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
measure: Changes From Baseline in Apolipoprotein B-100 Levels up to 52 Weeks
timeFrame: Baseline, Week 12, 24 and 52
Other outcomes:
Locations:
city: Seatlle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Chicoutimi
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Ste-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Ouest-Montreal
country: Canada
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris Cedex 13
country: France
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Meibergdreef 9
country: Netherlands
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: