E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Activated PI3K delta Syndrome (APDS) |
|
E.1.1.1 | Medical condition in easily understood language |
Activated PI3K delta Syndrome (APDS) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 primary objective is to evaluate the safety and tolerability of UCB5857 in subjects with Activated phosphoinositide-3 kinase (PI3K) delta Syndrome (APDS). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the pharmacokinetic (PK) profile of UCB5857 in subjects with Activated phosphoinositide-3 kinase (PI3K) delta Syndrome (APDS). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject/legal representative is considered reliable and capable of adhering to the protocol (e.g. able to understand and complete diaries), visit schedule, or medication intake.
- Subject must have a confirmed genotypic diagnosis of APDS (i.e. proven pathogenic mutation in either the PIK3R1 or PIK3CD gene).
- Subjects must have had clinical findings and manifestations compatible with APDS such as nodal and/or extranodal lymphoproliferation, history of repeated oto-sinopulmonary infections and/or organ dysfunction (e.g., lung, liver)
|
|
E.4 | Principal exclusion criteria |
1. Subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 30 days or is currently participating in another study of an IMP (or a medical device). 2. Subject has a history of allogeneic bone marrow transplantation. 3. Subject has no history of any clinical manifestations in last 12 months. 4. Subject tests positive for human immunodeficiency virus Type 1 or Type 2, hepatitis B surface antigen, or hepatitis C virus antibody. 5. Subject whose only clinical manifestations in the last 12 months are due to advanced bronchiectasis (declining lung function, 3 or more recurrent exacerbations, lung abscess, pneumothorax for repeating cough). 6. Subject who has a severe (life-threatening) infection during the screening period. 7. Subject who have lymphoma at the time of the screening or have been treated for lymphoma in the previous 5 years prior Screening (Visit 1). 8. Subject is female and is breast-feeding, pregnant, or plans to become pregnant or to start breastfeeding during the study or within 3 months following last dose of IMP. 9. Subject has WBC<2000/mm3, or absolute neutrophil count <1000/mm3 at Screening (Visit 1). 10. Subject has a history of chronic alcohol or drug abuse within the previous 6 months. 11. Subject has any relevant medical or psychiatric condition that could jeopardize or would compromise the subject’s ability to participate in this study. 12. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in this protocol. 13. Subject has been treated with any mTOR inhibitors (unless washed out, approximately 6 weeks). 14. Subject has a history of inflammatory bowel disease, peptic ulcers, or recurrent colitis including rectal bleeding (within 1 year prior to Screening [Visit 1]). 15. Subject has a body weight of less than 20 kg at Screening (Visit 1). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety variables The safety variables will include: • Incidence of AEs • Incidence of SAEs • Changes from Baseline in safety laboratory tests (serum chemistry, haematology, and urinalysis) at the time points measured • Change from Baseline in vital sign parameters (systolic and diastolic blood pressure, temperature, pulse rate and respiratory rate) and body weight at the time points measured • Change from Baseline in ECG parameters at the time points measured • Physical examination findings.
Pharmacokinetic variable The PK variable will be the plasma concentration of UCB5857. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the time points measured. |
|
E.5.2 | Secondary end point(s) |
Please refer to the study variables of the Clinical Trial Protocol. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to the study variables of the Clinical Trial Protocol. |
|
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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
A phase 1b study to evaluate the safety and tolerability of UCB5857 in subjects with APDS |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
|
The end of the study is defined as the date of the last visit (or follow-up telephone call) of the last subject in the study. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |