E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive Precocious Puberty Associated with McCune Albright Syndrome |
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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 | 10044701 |
E.1.2 | Term | True precocious puberty |
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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 |
The primary objective of this trial is composed of two components A safety and efficacy component and a pharmacokinetics PK component. All patients fulfilling the eligibility criteria will participate in both components of the trial. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include assessments of pubertal progression through Tanner Staging and predicted adult height for children over age six. The presence of a MAS associated Gsa mutation will be assessed by molecular analysis provided separate specific consent is obtained. No other genetic analysis will be performed with these specimens. The participation of patients and investigative sites in this analysis will be voluntary and any individual patient or site decision not to participate will not exclude them from this clinical study. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Diagnosis of McCune-Albright Syndrome based on having the following clinical criteria Precocious puberty evident before the age of 8 years And at least one of the following clinical criteria Cafe au lait spots Fibrous dysplasia Confirmation of Gsa mutation 2. Progressive precocious puberty associated with MAS. Progressive precocious puberty will be defined as o An increase of at least one in the breast Tanner Stage over the observation period and/or o The development or persistence of vaginal bleeding during the observation period. 3. At least one of the following two criteria must also be fulfilled o Advanced bone age defined as, bone age of at least 12 months beyond chronological age at the time of screening. o Rapid growth rate A growth rate over the observation period that is more than 2 standard deviations above the mean for age, where the growth rate is defined as the change in height or length in cm divided by the change in time annualized over years . |
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E.4 | Principal exclusion criteria |
1. Male gender 2. Any prior treatment of PPP associated with MAS with fulvestrant 3. Concomitant treatment of PPP associated with MAS, with the exception of bisphosphonates for fibrous dysplasia and GnRH analogs in the case of CPP 4. Liver function tests AST, ALT at screening 3 the upper limit of the reference range for age 5. Platelet count at screening less than 100 109/L 6. International normalized ratio INR greater than 1.6. 7. History of bleeding diathesis or long-term anticoagulant therapy other than antiplatelet therapy 8. Any severe concomitant condition that makes it undesirable for the patient to participate in this study 9. Known hypersensitivity to any component of the study drug product |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in annualized number of vaginal bleeding days on treatment compared to baseline. - Proportion of patients with baseline vaginal bleeding who experienced 50 reduction in the number of vaginal bleeding days on treatment - Proportion of patients with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 6-month trial period and over the whole 12-month trial - Change in rate of increase in bone age on treatment compared to baseline - Change in growth rate on treatment compared to baseline |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
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.8.5 | 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 | 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 | Information not present in EudraCT |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |