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

This study has been terminated.
(Interim analysis suggested that size of benefit anticipated from continued participation of patients in Part B no longer supported trial extension beyond Part A)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01589237
First received: April 27, 2012
Last updated: September 26, 2016
Last verified: September 2016
  Purpose
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).

Condition Intervention Phase
Familial Chylomicronemia Syndrome (FCS) (HLP Type I)
Drug: LCQ908
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Patients With Any Adverse Events, Serious Adverse Events and Death [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes From Baseline in Triglyceride Levels up to 52 Weeks [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 12, 24 and 52 ] [ Designated as safety issue: No ]
    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.


Enrollment: 38
Study Start Date: February 2013
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCQ908
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.
Drug: LCQ908

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589237

Locations
United States, Washington
Novartis Investigative Site
Seatlle, Washington, United States, 98104
Canada, Quebec
Novartis Investigative Site
Chicoutimi, Quebec, Canada, G7H 7P2
Novartis Investigative Site
Ste-Foy, Quebec, Canada, G1V4M6
Canada
Novartis Investigative Site
Ouest-Montreal, Canada, H2W1R7
France
Novartis Investigative Site
Nantes, France, 44093
Novartis Investigative Site
Paris Cedex 13, France, 75651
Germany
Novartis Investigative Site
Hamburg, Germany, 20246
Netherlands
Novartis Investigative Site
Meibergdreef 9, Netherlands, 1105 AZ
South Africa
Novartis Investigative Site
Cape Town, South Africa, 7925
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M13 9NT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01589237     History of Changes
Other Study ID Numbers: CLCQ908B2305  2012-000802-32 
Study First Received: April 27, 2012
Results First Received: June 17, 2016
Last Updated: September 26, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Netherlands: European Medicines Agency
France : European Medicines Agency
Germany: European Medicines Agency
Spain:European Medicines Agency
United Kingdom:European Medicines Agency
South Africa: Medicines Control Council

Keywords provided by Novartis:
Familial Chylomicronemia Syndrome (FCS) (HLP type I)
LCQ908

Additional relevant MeSH terms:
Syndrome
Hyperlipoproteinemia Type I
Disease
Pathologic Processes
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on December 06, 2016