E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Chest Syndrome (ACS) in At-Risk patients with Sickle Cell Disease (SCD) and Vaso-occlusive Crisis (VOC) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051895 |
E.1.2 | Term | Acute chest syndrome |
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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 determine the safety and tolerability of different doses of A-001 therapy when administered as a 2-day continuous infusion to SCD patients at-risk for ACS. |
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E.2.2 | Secondary objectives of the trial |
To determine the pharmacokinetic profile of A-001 in SCD patients. To confirm the ability of A-001 infusion to suppress serum sPLA2 activity in SCD patients with elevated serum sPLA2. To determine the efficacy of A-001 infusion in preventing ACS in SCD patients with the combination of VOC, fever, and elevated serum sPLA2. To determine the efficacy of A-001 infusion in reducing pain during VOC. To select the dose(s) to carry forward into pivotal trials.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Hb SS, Hb SC, sickle ß-thalassemia, sickle ß+ -thalassemia - Pain consistent with VOC (clinical judgment) and not attributable to other causes. - Serum sPLA2 level ≥100 ng/mL (measured on-site) - Fever defined as oral temperature ≥38.0°C - US and UK: age ≥12 years (through adult) |
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E.4 | Principal exclusion criteria |
- New (or suspected new) pulmonary infiltrate diagnosed by chest radiography - Pregnancy or breastfeeding - Known hypersensitivity to any of the active constituents of the A-001 or the IV multivitamin preparation (placebo) - Renal dysfunction: creatinine >1.2 mg/dL for age 18 or less, creatinine >1.5 mg/dL for over age 18 - Hepatic dysfunction (ALT >2 × upper limit of normal) - Acute neurologic dysfunction - Any medical condition for which transfusion may be needed imminently, and/or hemoglobin < 5 g/dL. - Red blood cell transfusion within 30 days of entry into the study - Unwillingness to sign consent form, or if a minor, unwillingness of parent/guardian to sign consent form - Parenteral or oral corticosteroid therapy (inhaled steroids acceptable) within 7 days of enrollment - Treatment with any investigational drug or device in the last 30 days - Any other current or past medical condition that might significantly affect pharmacodynamic responses to the administered drug, or any imminently life-threatening illness
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of A-001 in SCD patients with VOC |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | Information not present in EudraCT |
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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |