A study to Evaluate the Safety, Tolerability and Efficacy of an investigational drug Isavuconazonium Sulfate for the Treatment of Invasive Fungal Infections

Phase 1

Conditions: Invasive Aspergillosis and Invasive Mucormycosis
MedDRA version: 20.1Level: LLTClassification code 10062642Term: Invasive mycosisSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2018-003975-36-DE

Lead Sponsor: Astellas Pharma Global Development, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 30

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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