E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Invasive Aspergillosis and Invasive Mucormycosis |
|
E.1.1.1 | Medical condition in easily understood language |
Invasive Fungal infections |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062642 |
E.1.2 | Term | Invasive mycosis |
E.1.2 | System Organ Class | 100000004862 |
|
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 |
Safety Objective To evaluate the safety and tolerability of isavuconazonium sulfate in pediatric subjects
Efficacy Objective To assess the efficacy of isavuconazonium sulfate for the treatment of invasive aspergillosis (IA) or invasive mucormycosis (IM) in pediatric subjects
Pharmacokinetic Objective To evaluate the pharmacokinetics of isavuconazole by monitoring the plasma concentrations in pediatric subjects during treatment with isavuconazonium sulfate |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Institutional Review Board (IRB)-approved written informed consent and privacy language as required per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) must be obtained from the subject's parent or legal guardian and, if required, subject's assent, prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Male or female subject 1 year to < 18 years of age diagnosed with IA or IM. A positive diagnosis is defined as follows: - Proven, probable or possible invasive fungal infection (IFI) per the European Organisation for Research and Treatment of Cancer/Mycoses Study Group [EORTC/MSG], 2008 criteria Note: Subjects with "possible" IFI will be eligible for enrollment; however, diagnostic tests to confirm the invasive fungal disease as "probable" or "proven" according to the EORTC/MSG criteria should be completed within 10 calendar days after the first dose of study drug - Note: In addition to the criteria set for mycological criteria by the EORTC/MSG in 2008, and only for subjects with an underlying hematologic malignancy or recipients of hematopoietic stem cell transplant who also have clinical and radiologic features consistent with invasive fungal infection, the following are acceptable: i. Galactomannan (GM) levels (optical density index) meeting the below criteria are acceptable mycological evidence for enrollment or upgrading the diagnosis to probable IA: 1. A single value for serum or bronchoalveolar lavage (BAL) fluid of ≥ 1.0 or 2. Two serum GM values of ≥ 0.5 from 2 separate samples 3. Subject has sufficient venous access to permit intravenous administration of study drug or ability to swallow oral capsules. 4. A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: a. Not a subject who is of childbearing potential as defined in [Appendix 12.3 Contraception Requirements]. OR b. Subject who is of childbearing potential who agrees to follow the contraceptive guidance as defined in [Appendix 12.3 Contraception Requirements] throughout the treatment period and for at least 30 days after the final study drug administration. 5. Female subject who is of childbearing potential must agree not to breastfeed starting at screening and throughout the study and for 30 days after the final study drug administration. 6. Female subject who is of childbearing potential must not donate ova starting at screening, throughout the study, and for 30 days after the final study drug administration. 7. A male subject with female partner(s) of childbearing potential must agree to use contraception as detailed in [Appendix 12.3 Contraception Requirements] during the treatment period and for at least 30 days after the final study drug administration. 8. Male subject must not donate sperm starting at screening and throughout the study and for 30 days after the final study drug administration. 9. Subject and subject’s parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment with the exception of oncology trials. Waivers to the inclusion criteria will NOT be allowed. |
|
E.4 | Principal exclusion criteria |
1. Subject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal ECG. 2. Subject has evidence of hepatic dysfunction defined as any of the following: - Total bilirubin ≥ 3 times the upper limit of normal (ULN) - Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 5 times the ULN - Known cirrhosis or chronic hepatic failure 3. Subject has used strong cytochrome P450 (CYP3A4) inhibitors or inducers such as ketoconazole, high dose ritonavir, rifampin/rifampicin, long acting barbiturates (e.g., phenytoin), carbamazepine and St. John’s Wort in the 5 days prior to the first dose of study drug. 4. Subject has another IFI other than possible, probable or proven IA or IM. 5. Subject has chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis. 6. Subject has received mould active systemic antifungal therapy, effective against the primary invasive mould infection, for more than 4 days during the 7 days preceding the first dose. Note: Prior use of prophylactic antifungal therapy is acceptable. In case of breakthrough IA while on prophylatic mould-active azole class drugs, additional documentation will be required to be submitted to the sponsor medical monitor or designee to approve subject enrollment. 7. Subject has known history of allergy, hypersensitivity or any serious reaction to any of the azole class antifungals, or any components of the study drug formulation. 8. Subject has any condition, which, in the investigator’s opinion, makes the subject unsuitable for study participation. 9. Subject is unlikely to survive 30 days in the investigator’s opinion. 10. Subject has received investigational drug, with the exception of oncology drug trials or trials with investigational drugs treating graft versus host disease, within 28 days or 5 half-lives, whichever is longer, prior to screening. Waivers to the exclusion criteria will NOT be allowed. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Safety outcomes will include AEs, vital signs, ECGs and laboratory parameters. 2. The primary efficacy endpoint will be all-cause mortality through day 42.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. AEs (Screening, (screening and day 1, 2, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84 or IA EOT and IA follow up); vital signs (screening and day 1, 2, 3, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84 or IA EOT), ECG (screening, day 1, 7, 14, 28, 56, 84 or IA EOT) and laboratory parameters (screening , Day 7, 28, 56, 84 or IA EOT) 2. Through day 42 |
|
E.5.2 | Secondary end point(s) |
1. The key secondary efficacy endpoint will be all-cause mortality through day 84 and EOT. 2. Additional secondary efficacy endpoints will be overall, clinical, radiological and mycological response through day 42, day 84 and EOT. 3. Other secondary endpoints encompass pharmacokinetic endpoints, including plasma trough (pre-dose) levels on days 7, 14, 21, 42 and 84 or EOT. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. through day 84 and EOT 2. through day 42, day 84 and EOT 3. on days 7, 14, 21, 42 and 84 or EOT. |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 |
United States |
Belgium |
Germany |
Italy |
Spain |
United Kingdom |
|
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
|
The end of the study is defined as the last visit or scheduled procedure shown in the schedule of assessments for the last study participant 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 | 6 |
E.8.9.1 | In the Member State concerned days | 20 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 20 |