E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Patients with partial lipodystrophy |
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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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053857 |
E.1.2 | Term | Partial lipodystrophy |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
To evaluate the efficacy of ISIS 304801 (300 mg once weekly) for reduction in severity of metabolic derangement in patients with FPL with hypertriglyceridemia and uncontrolled diabetes |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of ISIS 304801 in patients with FPL. To further evaluate the role of serum TGs in modulating insulin resistance in FPL patients and the impact of TGs reduction on adipose tissue distribution in FPL patients |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinical diagnosis of FPL plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia.
2. Diagnosis of type 2 diabetes mellitus as defined by the ADASMCD in 2015 made at least 12 weeks prior to the screening visit
3. Hypertriglyceridemia is defined as Fasting TG ≥ 500 mg/dL (5.7 mmol/L) at Screening and qualification visit. |
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E.4 | Principal exclusion criteria |
1. A diagnosis of generalized lipodystrophy
2. A diagnosis of acquired partial lipodystrophy (APL)
3. Acute pancreatitis within 4 weeks of Screening
4. History within 6 months of Screening of acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new onset angina), stroke, transient ischemic attack or unstable congestive heart failure requiring a change in medication
5. Major surgery within 3 months of Screening
6. Platelet count < lower limit of normal
7. Have any other conditions in the opinion of the investigator which could interfere with the patient participating in our completing the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will be the comparison of percent changes from Baseline to the primary analysis time point in fasting TG between ISIS 304801 300 mg once weekly group and placebo group in the Full Analysis Set (FAS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis time point is at the end of Month 3 where the value is defined as the average of Week 12 and Week 13 fasting assessments.
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E.5.2 | Secondary end point(s) |
The secondary endpoints include:
• Change from Baseline in HbA1c
• Change from Baseline in liver volume and hepatic steatosis (as assessed by MRI)
• Absolute change from Baseline in fasting TG
• Proportion of patients who achieve a ≥ 40% reduction in fasting TG
• Change from Baseline in fasting plasma glucose
• Reduction in insulin use |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of Month 3 where the value is defined as the average of Week 12 (Day 78) and Week 13 (Day 85) fasting assessments. The value at Month 6 is defined as the average of Week 25 and Week 26 and the value at Month 12 is defined as the average of Week 51 and Week 52 fasting assessments. |
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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 | Yes |
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 | 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) | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Belgium |
Brazil |
Canada |
France |
Germany |
Greece |
Italy |
Netherlands |
Portugal |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
|
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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 48 |