E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10040644 |
E.1.2 | Term | Sickle cell disease |
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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 the safety and tolerability of pentosan polysulfate sodium administered daily for three months to patients with sickle cell disease |
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E.2.2 | Secondary objectives of the trial |
1) To assess the pharmacodynamic activity of pentosan polysulfate sodium
2) To assess activity of pentosan polysulfate sodium on vascular endothelial injury and vasoocclusive pain associated with sickle cell disease.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be 18 years of age or older at the time of informed consent;
2. Have a diagnosis of homozygous sickle cell anemia or sickle cell-beta thalassemia;
3. Have had 2 - 10 documented pain crises in the past year (pain crises are defined as visits to a medical clinic, Emergency Department or hospital, being bedridden and requiring constant analgesia at home for at least three days, or having a three-day interruption of life’s activities [i.e., school, work, planned leisure activity] because of pain);
4. If female and of child bearing potential, have a negative serum or urine pregnancy test and be using an effective birth-control method with a history of reliability for the individual patient (use of misepristone is not allowed);
5. Be properly informed of the nature and risks of the clinical investigation, be willing and able to comply with all clinical investigation-related procedures and assessments, and sign an Institutional Review Board (EC) approved Informed Consent Form prior to entering the clinical investigation.
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E.4 | Principal exclusion criteria |
1. Have a history of abnormal bleeding, stroke, moya moya vascular malformations, or any other contraindication to anticoagulation; 2. Be currently taking anticoagulant or thrombolytic medication; 3. Be currently taking an endothelin receptor antagonist, e.g., bosentan (Tracleer®); 4. Have a known sensitivity or allergy to heparin or PPS; 5. Have a history of thrombocytopenia (platelet count < 100 x 103/mm3) induced by heparin or PPS; 6. Have had fewer than 2 documented pain crises in the past year; 7. Have had a pain crisis within one month of screening or randomization; 8. If currently on or recently discontinued hydroxyurea treatment, have initiated or discontinued treatment or changed regimen within the past 6 months; 9. Have had a transfusion within last 120 days or have HbA% > 15% from prior transfusion; 10. Creatinine levels > 2 mg/dL (176.8 mol/L); 11. ALT levels ≥ 5 times normal; 12. Platelet count < 100 x 103/mm3; 13. INR > 2.2; 14. Be unable to tolerate oral medications; 15. Have unreliable venous access; 16. Be noncompliant with regular care; 17. Have a positive pregnancy test, be currently lactating, or be trying to become pregnant; 18. Have participation in an investigational drug or medical device study within previous 30 days; 19. Have any other condition or circumstance that in the opinion of the Investigator makes the patient a poor candidate for participation in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
There are five outcomes to be measured in this study. 1) Changes in blood flow as measured by laser Doppler technology. Blood flow in the microcirculation will be measured in three places on the subject’s forearm. It is anticipated that a combination of the four measurements will be used in the calculation of the statistics to be used for this outcome. The SAP will define this outcome in detail. It is also possible to analyse this outcome as a multi-level clustered model with clustering at the forearm level (four measurements at different locations) and over time (measurements at multiple visits) to control for the inherent correlation within the forearm and within the same subjects measured repeatedly over time. 2) Change in circulating markers of blood vessel injury and inflammation: The change (as defined for outcome above) for each marker will be determined for use in descriptive analysis and in comparison of changes between treatment groups. 3) Change in frequency of pain: The change in frequency of pain will be calculated as a median with a non-parametric comparison of frequency between treatment groups due to the inherently non-normal distribution of pain scores. 4) Physician’s global assessment of response to treatment: This assessment would occur at every visit and would consist of a single reading ranging from -3 to +3. The change in this assessment would be calculated as the change from baseline represented in a multi-dimensional contingency table. 5) Change in the level of P-selectin blocking activity: The change in the P-selectin blocking activity for each patient from the baseline measure (b) of P-selectin to the P-selectin at visits (f) conducted at weeks -4, 0, 1, 4, 8, 12, and +4 will be determined as b-f for each f and used in descriptive analyses. In addition, a comparison between treatment groups of the change in P-selectin blocking activity will be conducted.
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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 | No |
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 | Yes |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |