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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040643 |
E.1.2 | Term | Sickle cell crisis |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of the administration of NAC over a period of 6 months in reducing the frequency of self reported, SCD related pain in daily life in patients with homozygous HbSS, HbSC, HbSβ+ or HbSβ0 SCD. |
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E.2.2 | Secondary objectives of the trial |
To assess the related severity of self reported SCD related pain in daily life over a period of 6 months
To assess the related incidence and severity of painful crises in daily life over a period of 6 months
To assess the related frequency and length of hospital admissions over a period of 6 months
To asses the health related quality of life over a period of 6 months
To assess related societal costs over a period of 6 months
To assess related changes in hematological markers over a period of 6 months
To assess the tolerability of NAC over a period of 6 months
To asses the frequency of use of pain medication at home over a period of 6 months
To asses the related frequency of SCD complications over a period of 6 months (e.g. acute chest syndrome)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age 12 years or older
- Sickle cell disease, either homozygous sickle cell disease (HbSS), HbSC sickle cell
disease, HbSβ0 or HbSβ+ thalassemia.
Genotype needs to be confirmed by high performance liquid chromatography.
- History of at least 1.0 painful crisis per year in the past 3 years.
A crisis will be defined here as a patient defined, painful, sickle cell related episode of at least 24 hours where a subject experienced significant impediments in his/her daily activities, and pain medication had to be taken. A visit to a medical facility is not obligatory in this definition.
- Written informed consent from patient/parent/guardian is given.
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E.4 | Principal exclusion criteria |
- Chronic blood transfusion or transfusion in the preceding 3 months
- Painful crisis in the last 4 weeks (with respect to the moment of inclusion).
A crisis will be defined as above; a patient defined, painful, sickle cell related episode of at least 24 hours where the subject experienced significant impediments in his/her daily activities, and pain medication had to be taken. A visit to a medical facility is not obligatory in this definition.
- Pregnancy, breast feeding or the desire to get pregnant in the following 7 months
- Known active gastric/duodenal ulcers
- Hydroxycarbamide (HC) treatment with unstable dose in the last 3 months or started on
HC shorter then 6 months prior to study.
- Known poor compliance in earlier trials regarding the completion of pain diaries.
- Insufficient compliance in run-in period.
Participants that do not show up for their follow-up visit without prior notice, that not bring
their diary or with less than 80% of the days in the pain diary filled in, will be excluded from participation in this trial and will not be randomized.
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E.5 End points |
E.5.1 | Primary end point(s) |
The main endpoint of this study, which formed the basis for statistical power calculations, is the frequency of SCD related pain in daily life in patients with SCD. Frequency of pain will be expressed in days per patient in proportion to the total time of intervention (6 months) per treatment group.
A pain day will be defined as:
• When the box “Yes, I have experienced pain” is checked in a daily diary.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The severity of SCD related pain in daily life. This will be defined using a 0-10 numerical rating scale (NRS) in the pain diary.
The frequency and severity of painful crises over a period of 6 months.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, 3 months and 6 months |
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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 | No |
E.6.5 | Efficacy | No |
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) | 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
| 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 | 4 |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |