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Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.

Primary Purpose

Familial Chylomicronemia Syndrome (FCS) (HLP Type I)

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LCQ908
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Familial Chylomicronemia Syndrome (FCS) (HLP Type I) focused on measuring Familial Chylomicronemia Syndrome (FCS) (HLP type I), LCQ908

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LCQ908

Arm Description

Patients initiated at 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose will be allowed. One down titration allowed from the highest dose attained.

Outcomes

Primary Outcome Measures

Number of Patients With Any Adverse Events, Serious Adverse Events and Death

Secondary Outcome Measures

Changes From Baseline in Triglyceride Levels up to 52 Weeks
Blood samples were collected for a fasting lipid panel, including total triglycerides. Lipid measurements were collected after a 12 hour (overnight) fast. The maintenance of effect was assessed on triglyceride levels during continued therapy with LCQ908 for up to 52 weeks. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Cholesterol Levels up to 52 Weeks
Blood samples were collected for a fasting lipid panel, including cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in HDL and Non HDL Cholesterol Levels up to 52 Weeks
Blood samples were collected for a fasting lipid panel, including HDL and non HDL cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Glycerol Levels up to 52 Weeks
Blood samples were collected for a fasting lipid panel, including glycerol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Free Fatty Acid Levels up to 52 Weeks
Blood samples were collected for a fasting lipid panel, including free fatty acid level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Apolipoprotein A1 Levels up to 52 Weeks
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein A1. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Apolipoprotein B-48 Levels up to 52 Weeks
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-48. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Changes From Baseline in Apolipoprotein B-100 Levels up to 52 Weeks
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-100. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.

Full Information

First Posted
April 27, 2012
Last Updated
September 26, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01589237
Brief Title
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

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
Interim analysis suggested that size of benefit anticipated from continued participation of patients in Part B no longer supported trial extension beyond Part A
Study Start Date
February 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Chylomicronemia Syndrome (FCS) (HLP Type I)
Keywords
Familial Chylomicronemia Syndrome (FCS) (HLP type I), LCQ908

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LCQ908
Arm Type
Experimental
Arm Description
Patients initiated at 10 mg/day. After at least 8 weeks of treatment with a dose, optional up-titration to the next possible dose will be allowed. One down titration allowed from the highest dose attained.
Intervention Type
Drug
Intervention Name(s)
LCQ908
Primary Outcome Measure Information:
Title
Number of Patients With Any Adverse Events, Serious Adverse Events and Death
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Changes From Baseline in Triglyceride Levels up to 52 Weeks
Description
Blood samples were collected for a fasting lipid panel, including total triglycerides. Lipid measurements were collected after a 12 hour (overnight) fast. The maintenance of effect was assessed on triglyceride levels during continued therapy with LCQ908 for up to 52 weeks. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Cholesterol Levels up to 52 Weeks
Description
Blood samples were collected for a fasting lipid panel, including cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in HDL and Non HDL Cholesterol Levels up to 52 Weeks
Description
Blood samples were collected for a fasting lipid panel, including HDL and non HDL cholesterol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Glycerol Levels up to 52 Weeks
Description
Blood samples were collected for a fasting lipid panel, including glycerol level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Free Fatty Acid Levels up to 52 Weeks
Description
Blood samples were collected for a fasting lipid panel, including free fatty acid level. Lipid measurements were collected after a 12 hour (overnight) fast. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Apolipoprotein A1 Levels up to 52 Weeks
Description
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein A1. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Apolipoprotein B-48 Levels up to 52 Weeks
Description
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-48. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52
Title
Changes From Baseline in Apolipoprotein B-100 Levels up to 52 Weeks
Description
Fasting blood samples were collected by direct venipuncture or an indwelling cannula to evaluate the drug effect on lipoprotein biomarkers such as Apolipoprotein B-100. For patients from LCQ908 arm of study CLCQ908A2212, baseline was the assessment obtained at Week 0 of current study. For patients from study CLCQ908B2302, baseline is defined as the average of values taken Day -3 and Week 0 (randomization) in study CLCQ908B2302. The geometric mean for the percentage (%) change is calculated from back-transforming the mean of the log transformed ratio to baseline values: (exp(mean of the log-transformed ratio to baseline values) -1)*100.
Time Frame
Baseline, Week 12, 24 and 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Subjects that either discontinue prematurely or complete the CLCQ908B2302 study after 52 weeks or FCS subjects who have previously completed study CLCQ908A2212. Exclusion Criteria: Subjects discontinued from the CLCQ908B2302 study for serious, potentially study drug related adverse events. Subjects from the CLCQ908B2302 study who have developed any other contraindication to participation (for example, renal failure) 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. 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. Subjects with type 1 diabetes mellitus or type 2 diabetes mellitus if HbA1C is ≥ 8.5%. Treatment with fish oil preparations within 4 weeks prior to randomization. Treatment with bile acid binding resins (i.e., colesevelam, etc) within 4 weeks prior to randomization. Treatment with fibrates within 8 weeks prior to randomization. Washout may occur following screening if required. Glybera [alipogene tiparvovec (AAV1-LPLS447X )] gene therapy exposure within the two years prior to screening. eGFR <45 ml/min/1.73m2 or history of chronic renal disease. Other protocol defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Seatlle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Novartis Investigative Site
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7P2
Country
Canada
Facility Name
Novartis Investigative Site
City
Ste-Foy
State/Province
Quebec
ZIP/Postal Code
G1V4M6
Country
Canada
Facility Name
Novartis Investigative Site
City
Ouest-Montreal
ZIP/Postal Code
H2W1R7
Country
Canada
Facility Name
Novartis Investigative Site
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Novartis Investigative Site
City
Paris Cedex 13
ZIP/Postal Code
75651
Country
France
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Meibergdreef 9
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M13 9NT
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.

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