E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Hypertriglyceridemia for the Prevention of Recurrent Acute Pancreatitis |
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E.1.1.1 | Medical condition in easily understood language |
Hypertriglyceridemia is the presence of high levels of fats called triglycerides in the blood which can cause inflammation of the pancreas |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020869 |
E.1.2 | Term | Hypertriglyceridaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the proportion of patients with elevated TGs, without Familial Chylomicronemia Syndrome (FCS) due to loss of function (LoF) mutations in lipoprotein lipase (LPL), and a history of hypertriglyceridemia (HTG)-associated acute pancreatitis (AP*) who experience a recurrent episode of AP after treatment with evinacumab versus placebo. *Includes adult patients with 1) elevated baseline fasting TGs >880 mg/dL and history of 1 HTGassociated AP within 24 months of screening or 2) elevated baseline fasting TG values >500 mg/dL in patients with a history of 2 or more HTG-associated AP within 24 months or 3) elevated baseline fasting TG values >500 mg/dL with a prior documented fasted TG values >1000 mg/dL and a history of 1 or more HTG- associated AP within 24 months. All participants are without FCS due to LPL loss of function mutations. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • To determine the change in the standard lipid profile after therapy with evinacumab versus placebo • To determine the changes in specialty lipoprotein parameters (ApoC3, ApoB48, ApoB100, and nuclear magnetic resonance [NMR] lipid profile) after therapy with evinacumab versus placebo • To measure the number of AP episodes per patient • To assess the safety and tolerability of evinacumab • To assess the potential immunogenicity of evinacumab • To assess the concentrations of total evinacumab and total angiopoietin-like 3 (ANGPTL3) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Future Biomedical Research (FBR) substudy (Optional): The samples may be utilized for FBR that may or may not be directly related to the study, including being used as reference samples and assay development or validation.
Genomics sub-study (Optional): The purpose of the pharmacogenomic analyses is to identify genomic associations with clinical or biomarker response to evinacumab, other HTG clinical outcome measures, and possible AEs |
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E.3 | Principal inclusion criteria |
Key Inclusion Criteria:
1. Adults 18 to 80 years of age without FCS due to LPL loss of function mutations 2. Documented history of 1 HTG-associated AP episode within 24 months of screening (can be determined by study investigator; does not need to be confirmed by independent adjudication committee) 3. Fasting serum TG value >880 mg/dL (10 mmol/L) on 2 occasions at least 2 days apart determined during the screening period.Triglyceride measurement can be repeated once for values >500 mg/dL (5.6 mmol/L) but <880 mg/dL (10 mmol/L) OR Fasting serum TG value >500 mg/dL (5.6 mmol/L) determined during the screening period in patients with a history of 2 or more HTGassociated AP episodes within 24 months of screening OR Fasting serum TG value >500 mg/dL (5.6 mmol/L) determined during the screening period and a documented fasted serum TG value >1000 mg/dL (11.3 mmol/L) and a history of 1 or more HTG-associated AP episode(s) within 24 months of screening. 4. Stable dose of lipid-lowering therapy (≥8 weeks) and willingness to maintain a stable regimen throughout the study 5. Body mass index ≥18.0 and ≤45.0 kg/m2 6. Compliance with a stable diet and exercise regimen at screening and willingness to continue the diet through the end of the study 7. Willing and able to comply with clinic visits and study-related procedures 8. Provide informed consent signed by study patient or legally acceptable representative 9. Able to understand and complete study-related questionnaires
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria:
1. Hospitalization for AP within 4 weeks of screening 2. Known genetic FCS defined as homozygous or compound heterozygous LoF mutations in LPL as defined in the protocol 3. Symptomatic gallstone disease within 6 months prior to screening as defined in the protocol 4. Use of any medication or nutraceutical known to alter serum lipids which has not been part of a stable therapeutic regimen for at least 8 weeks, and there are no plans to change the regimen during the study 5. Presence of any clinically significant, uncontrolled endocrine disease known to influence serum lipids as defined in the protocol
Note: Other protocol-defined Exclusion Criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of patients with at least 1 positively adjudicated AP episode during the 52 weeks of the DBTP. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
2. Percent change in ApoC3 [Time Frame: Baseline to week 52] 3. Percent change in fasting triglycerides (TGs) [Time Frame: Baseline to week 52] 4. Percent change in total cholesterol (TC) [Time Frame: Baseline to week 52] 5. Percent change in non-high-density lipoprotein cholesterol (non-HDL-C) [Time Frame: Baseline to week 52] 6. Percent change in ApoB48 [Time Frame: Baseline to week 52] 7. Percent change in ApoB100 levels [Time Frame: Baseline to week 52] 8. Percent change in nuclear magnetic resonance (NMR)-determined particle size and number [Time Frame: Baseline to week 52] 9. Number of independently adjudicated episodes of AP per patient [Time Frame: Up to 52 weeks] |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 - 8. Baseline to week 52 9. Up to 52 Weeks |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
United States |
Austria |
Netherlands |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |