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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 assess efficacy of treatment with L-glutamine on sickling as evaluated by change in Point of Sicking (expressed in mmHg), as quantified by the Oxygenscan. Efficacy is defined as the lowest PoS measured during the treatment period relative (%) to the mean PoS at baseline (before treatment). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of L-glutamine treatment on: - Clinical characteristics such as fatigue and pain. - RBC degradation as expressed by phosphatidylserine (PS) exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes and hemoglobin - Oxidative stress as expressed by intracellular metabolomics and by plasma levels of AGEs - In vitro adhesion of RBCs to laminin - Endothelial activation as reflected by plasma levels of soluble vascular adhesion molecule-1 (sVCAM-1) and von Willebrand factor antigen (VWF:Ag)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- High performance liquid chromatography (HPLC) conformed HbSS or HbSβ0-thal - age 12 - 70 years - Able and willing to give informed consent - Good performance status (ECOG 0 or 1) |
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E.4 | Principal exclusion criteria |
- Poor performance status (ECOG > 1) - HIV infection - Active acute infection - Inflammatory disease - Pregnancy - Blood cell transfusion within 4 months prior to screening - Vaso-occlusive painful crisis within 4 week prior to screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy is defined as the lowest PoS measured during the treatment period relative (%) to the mean PoS at baseline (before treatment). The primary endpoint of the study is the relative (percentage) decrease in PoS at 12 weeks of treatment as compared to baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline and after 12 weeks of treatment |
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E.5.2 | Secondary end point(s) |
- The absolute decrease in PoS at 12 weeks of treatment as compared to baseline. - Changes in daily (chronic) pain score (NRS) and frequency of pain at 12 weeks, compared to baseline - Changes in PS exposure on the outer surface of RBC membrane and markers of hemolysis (cell-free heme, lactate dehydrogenase (LDH), bilirubin, reticulocytes) and hemoglobin at 12 weeks of treatment as compared to baseline. - Changes in oxidative stress (as expressed by intracellular metabolomics and by plasma levels of AGEs) after 12 weeks of treatment as compared to baseline. - Changes in in vitro adhesion of RBCs to laminin after 12 weeks of treatment as compared to baseline. - Changes in plasma levels of sVCAM-1 and VWF:Ag (as markers of endothelial activation) at 12 weeks of treatment compared to baseline.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline and after 12 weeks of treatment |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |