| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Familial Chylomicronemia Syndrome (FCS) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Familial Chylomicronemia Syndrome |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051598 |
| E.1.2 | Term | Chylomicrons |
| E.1.2 | System Organ Class | 10022891 - Investigations |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The purpose of this study is to determine whether LCQ908 is effective and safe in lowering triglycerides in subjects with Familial Chylomicronemia Syndrome (FCS) (Hyperlipoproteinemia [HLP] type I). Data from this study will be used to support a registration submission of LCQ908 20 mg and 40 mg as treatment of chylomicronemia in subjects with FCS (HLP Type I). |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Written informed consent must be performed before any assessment is performed for Period I
- Male and female subjects ages at least 18 years of age
- Fasting TG ≥ 8.4 mmol/L (750 mg/dL) at Screening
- An established diagnosis of Familial Chylomicronemia Syndrome (HLP Type I) confirmed through ultracentrifugation or by documented medical history of a fasting TG ≥ 8.4 mmol/L (750 mg/dL) and by documentation of any of the following at Screening Period:
a. Confirmed homozygote or compound heterozygote for known loss-of-function mutations in Type I-causing genes (such as LPL, apoCII, GPIHBP1 or LMF1)
b. Post heparin plasma LPL activity of ≤ 20% of normal
c. Confirmed presence of LPL inactivarting antibodies
-History of pancreatitis |
|
| E.4 | Principal exclusion criteria |
- Although a history of pancreatitis is required, this must be inactive for at least 1 week prior to Screening Visit
- 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 4 weeks prior to randomization
- Glybera [alipogene tiparvovec (AAV1-LPLS447X)] gene therapy exposure within two years prior to screening
- History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past 1 year, regardless of whether there is evidence of local recurrence or metastases.
- Any surgical or medical conditions, acute or unstable chronic disease which may, based on investigators opinion, jeopardize the patient in case of participation in the study or might significantly alter the absorption, distribution, metabolism or excretion of the study drug. History of drug or alcohol abuse within the 12 months prior to randomization or evidence of such abuse at screening. Evidence of liver disease or liver injury as indicated by abnormal liver function tests such as AST or ALT, or serum bilirubin.
- Use of any other investigational drugs at the time of screening, or within 30 days or 5 half-lives of enrollment, whichever is longer
-eGFR < 30ml/min/1.73m2 or history of chronic renal disease
- Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer of required by local regulations or any other limitation of participation based on local regulations
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
- 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 positive laboratory test.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 100 days after discontinuation of investigational study drug. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Percent change in fasting triglycerides from Baseline to 12 weeks
Blood samples will be collected for a fasting lipid panel, including triglycerides. The primary efficacy variable is defined as percent change in fasting triglycerides from baseline to the end of the double-blind treatment period (the measurement value at 12 weeks or the last available post-baseline measurement value during the double-blind treatment period, if the 12-week value is missing). Baseline is defined as the average of fasting triglyceride values at day -3 and day 1. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
* Proportion of patients with Familial Chylomicronemia Syndrome (FCS) responding to investigational treatment
Response to investigational treatment at a post-baseline visit will be characterized in three different ways:
- achieving fasting triglycerides of at least 40 % from baseline or final fasting triglycerides <8.4 mmol/L (750mg/dL)
- achieving fasting triglycerides of at least 40 % from baseline
- achieving fasting triglycerides < 8.4 mmol/L (750mg/dL)
* Proportion of subjects achieving fasting triglycerides (TG) target thresholds including TG <1000 mg/dL (11.4 mmol/L) or <2000 mg/dL (22.8 mmol/L)
* Pharmacokinetics of LCQ908 - Through Concentration (Cmin) (at weeks 0,4,8,12,16,20,24,36,52 after dosing)
*Pharmacokinetics of LCQ908-Area under the plasma concentration curve AUC (0-8hour) (at weeks 0,4,8,12,16,20,24,36,52 after dosing) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks, 24 weeks, 52 weeks |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| South Africa |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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