E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 objectives of this study are: 1. To establish the clinical efficacy of ICA-17043 when compared to placebo (with hydroxyurea (HU) as background therapy) in patients with sickle cell disease who have had ≥ 2 acute sickle-related painful crises within the preceding 12 months;
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E.2.2 | Secondary objectives of the trial |
To obtain further safety information on the chronic dosing of ICA-17043 in patients with sickle cell disease; and
To obtain ICA-17043 plasma concentrations following chronic dosing to assess steady-state ICA-17043 plasma concentrations in patients with sickle cell disease. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with sickle cell disease (SCD) meeting all of the following criteria will be considered for admission to the study: 1. 16 to 65 years of age (inclusive) with a minimum weight of 40 kilograms for those patients aged 16-17 (inclusive); 2. Male, or female not capable of becoming pregnant or using appropriate birth control method; 3. Negative serum pregnancy test on Screening Day and a negative urine pregnancy test (dipstick) prior to dosing on Day 1 (for females); 4. Confirmed medical history or diagnosis of SCD (e.g. HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia patients); 5. Have received HU for preceeding 12 months and be dose stabilised with HU for at least 90 days prior to day 1; 6. Have a history of at least two or more acute sickle-related painful crises requiring a visit to a medical facility within the preceding 12 months; 7. Acceptable study admission chest x-ray upon enrollment (i.e., no evidence of acute pulmonary infiltrates). Most recent chest x-ray must be no more than 90 days prior to Day 1; 8. Clinically acceptable 12-lead ECG on screening, with a normal QTc interval for this population (less than or equal to 475 msec) ; 9. Clinically acceptable medical history, physical examination, vital signs, clinical laboratory tests (see Exclusion Criteria #8, below, for specific laboratory exclusions); and 10. Have willingly given written informed consent (and/or assent for those patients under 18 years of age) to participate in this investigation.
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study: 1. Any patient who has experienced any allergic reaction to any drugs which, in the opinion of the investigator, suggests an increased potential for a hypersensitivity to ICA-17043; 2. Any patient who has received ICA-17043 in a previous investigational study; 3. Any patient on a chronic transfusion program, has had a transfusion within 30 days prior to Day 1 or an exchange transfusion 60 days prior to day 1; 4. Any patient whose hemoglobin is < 4.0 g/dL or >11.0 g/dL 5. Any patient considering or scheduled to undergo a major surgical procedure during the duration of the study; 6. Patients with significant active and poorly controlled (unstable) cardiovascular (including atrial or ventricular cardiac arrhythmias or long QT syndrome), neurologic, endocrine, hepatic, or renal disorders. Laboratory abnormalities that will lead to exclusion are:
System Laboratory Test Excluded Abnormal Range Renal Creatinine more than or equal to 1.5 mg/dL Liver Total bilirubin more than or equal to 20.0 mg/dL ALT (SGPT) more than or equal to 2x upper limit of normal range
7. Any patient diagnosed with cancer (except non-melanoma skin cancer) within the last 5 years; 8. Ingestion of any investigational medication within 30 days prior to Day 1, or plans for participating in another investigational drug trial for the duration of the study; 9. One or more of the following markers of hepatitis a. a history of hepatitis B or C clinical infection; b. a positive test for heptitis B surface antigen; OR c. a positive test for hepatitis C antibody AND has evidence of active liver disease (e.g., elevated liver enzymes, signs and symptoms of portal hypertension including coagulopathy, ascites, encephalopathy or histopathological evidence of active liver inflammation from a liver biopsy); 10. Subjects with a history of HIV infection or demonstration of HIV antibodies; 11. A positive qualitative urine drug test at Screening (for cocaine, phencyclidine (PCP), or amphetamines); and 12. Any patient with a serious mental (including psychosis) or physical illness, which, in the opinion of the investigator would compromise participation in the study (e.g. impaired mental capacity, alcoholism);
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy end point will be the rate of acute sickle-related painful crises. The “painful crisis” rate for a patient is defined as the total number of painful crises divided by the number of months in which the patient was receiving treatment (i.e., the individual’s treatment phase). An acute sickle-related painful crisis, hereafter will be referred to as a “painful crisis”. A “painful crisis” must meet all of the criteria below: • an acute episode of pain; • no known cause for pain other than a vaso-occlusive event; • requiring a visit to a medical facility; and • requiring treatment with a parenteral, oral, or transdermal narcotics (including opiates), or parenteral NSAIDs.
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |