A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03816176

Collaborator

(none)

Enrollment

Locations

Arm

44.3

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of isavuconazonium sulfate in pediatric participants.

Condition or Disease	Intervention/Treatment	Phase
Invasive Mucormycosis Invasive Aspergillosis	Drug: Isavuconazonium sulfate Drug: Isavuconazonium sulfate	Phase 2

Detailed Description

Treatment will begin on Day 1 and then participants will be followed for 60 days post-last dose for safety. Treatment will be administered until the participant has a successful outcome or for a maximum duration of 84 days (IA) or 180 days (IM), whichever occurs first.

Participants will receive a loading regimen of isavuconazonium sulfate (via intravenous or oral administration at the investigator's discretion), which consists of a dose every 8 hours (± 2 hours) on Days 1 and 2 (for a total of 6 doses), followed by once daily maintenance dosing for up to 84 days (IA) or 180 days (IM) of dosing. The first maintenance dose should start 12 to 24 hours after the administration of the last loading dose. Subsequent maintenance doses will be administered once daily (24 hours ± 2 hours from the previous maintenance dose). The oral formulation can only be given to subjects 6 years to < 18 years of age and with a body weight of at least 12 kg. Subjects who are discharged from the hospital with oral capsules for at-home administration must return weekly for study drug accountability and to receive new oral dosing supplies. Subjects who begin oral administration are to complete the oral dosing acceptability assessment after ingesting their first oral dose.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Open-Label, Non-Comparative, Multicenter Study to Evaluate the Safety and Tolerability, Efficacy and Pharmacokinetics of Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Subjects

Actual Study Start Date :

Aug 22, 2019

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Apr 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isavuconazonium sulfate Participants will receive a loading dose of isavuconazonium sulfate (via intravenous or oral administration at the investigator's discretion) every 8 hours (± 2 hours) on Days 1 and 2 followed by once-daily maintenance dosing	Drug: Isavuconazonium sulfate Intravenous (IV) infusion Other Names: Cresemba Drug: Isavuconazonium sulfate Oral capsule Other Names: Cresemba

Arm

Intervention/Treatment

Experimental: Isavuconazonium sulfate

Participants will receive a loading dose of isavuconazonium sulfate (via intravenous or oral administration at the investigator's discretion) every 8 hours (± 2 hours) on Days 1 and 2 followed by once-daily maintenance dosing

Drug: Isavuconazonium sulfate

Intravenous (IV) infusion

Other Names:

Cresemba

Drug: Isavuconazonium sulfate

Oral capsule

Other Names:

Cresemba

Outcome Measures

Primary Outcome Measures

Safety assessed by Adverse Events (AEs) [Up to 240 days]
An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product.
Number of participants with vital sign abnormalities and /or adverse events [Up to 84 days]
Number of participants with potentially clinically significant vital sign values
Safety assessed by 12- lead electrocardiogram (ECG) [Up to 84 days]
A 12-lead, resting ECG will be recorded after participant has remained supine for at least 5 minutes. The results (normal, abnormal not clinically significant, abnormal clinically significant) are to be recorded
Number of participants with laboratory value abnormalities and/or adverse events (AEs) [Up to 84 days]
Number of participants with potentially clinically significant laboratory values
All-cause mortality through Day 42 [Up to 42 days]
Each participant will be classified as either a death or alive

Secondary Outcome Measures

All-cause mortality through Day 84 [Up to 84 days]
Each participant will be classified as either a death or alive
All-cause mortality at End of Treatment (EOT) [Up to 180 days]
Each participant will be classified as either a death or alive
Overall response through Day 42 [Up to 42 days]
Overall response through day 42 will be based on clinical, mycological, and radiological response
Overall response through Day 84 [Up to 84 days]
Overall response through day 84 will be based on clinical, mycological, and radiological response
Overall response at EOT [Up to 180 days]
Overall response through EOT will be based on clinical, mycological, and radiological response
Clinical response through Day 42 [Up to 42 days]
Each participant will be assessed for changes in clinical sign and symptoms of infection(s)
Clinical response through Day 84 [Up to 84 days]
Each participant will be assessed for changes in clinical sign and symptoms of infection(s)
Clinical response at EOT [Up to 180 days]
Each participant will be assessed for changes in clinical sign and symptoms of infection(s)
Radiological response through Day 42 [Up to 42 days]
Each participant will be assessed for radiological evidence of fungal disease
Radiological response through Day 84 [Up to 84 days]
Each participant will be assessed for radiological evidence of fungal disease
Radiological response at EOT [Up to 180 days]
Each participant will be assessed for radiological evidence of fungal disease
Mycological response through Day 42 [Up to 42 days]
Each participant will be assessed for mycological evidence of fungal disease
Mycological response through Day 84 [Up to 84 days]
Each participant will be assessed for mycological evidence of fungal disease
Mycological response at EOT [Up to 180 days]
Each participant will be assessed for mycological evidence of fungal disease
Pharmacokinetics of isavuconazole in plasma: trough concentration (Ctrough) [Up to 84 days]
Ctrough will be recorded from the pharmacokinetic (PK) plasma samples collected

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject diagnosed with IA or IM. A positive diagnosis is defined as follows:
Proven, probable or possible 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 (HSCT) who also have clinical and radiologic features consistent with invasive fungal infection, the following are acceptable:
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
1. Two serum GM values of ≥ 0.5 from two separate samples
Subject has sufficient venous access to permit intravenous administration of study drug or the ability to swallow oral capsules
A female subject is eligible to participate if not pregnant and at least one of the following conditions applies:
Not a subject who is of childbearing potential, OR
Subject who is of childbearing potential who agrees to follow a contraceptive guidance throughout the treatment period and for at least 30 days after the final study drug administration
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

Exclusion Criteria:

Subject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal ECG
Subject has evidence of hepatic dysfunction defined as any of the following:
Total bilirubin (TBL) ≥ 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
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
Subject has another IFI other than possible, probably or proven IA or IM
Subject has chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis
Subject has received mould active systemic antifungal therapy, effective against the primary IMI, for more than four days during the seven days preceding the first dose
Note: Prior use of prophylactic antifungal therapy is acceptable. In case of breakthrough IA while on prophylactic mould-active azole class drugs, additional documentation will be required to be submitted to the sponsor medical monitor or designee to approve subject enrollment
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
Subject has any condition which makes the subject unsuitable for study participation
Subject is unlikely to survive 30 days
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 five half-lives, whichever is longer, prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miller Children's Hospital	Long Beach	California	United States	90806
2	Children's Hospital, Los Angeles	Los Angeles	California	United States	90027
3	University of California - Los Angeles	Los Angeles	California	United States	90095
4	Children's Hospital of Orange County	Orange	California	United States	92868
5	Children's National Medical Center	Washington	District of Columbia	United States	20010
6	Nicklaus Children's Hospital	Miami	Florida	United States	33155
7	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
8	University of Louisville	Louisville	Kentucky	United States	40202
9	Children's Hospital, LSUHSC, New Orleans	New Orleans	Louisiana	United States	70118
10	Detriot Medical Center-Children's Hospital of Michigan	Detroit	Michigan	United States	48201
11	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
12	SUNY Upstate Medical University	Syracuse	New York	United States	13210
13	Duke University	Durham	North Carolina	United States	27705
14	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
15	St Jude Children's Res Hospital	Memphis	Tennessee	United States	38105
16	Site BE32001	Gent		Belgium	9000
17	Site BE32002	Leuven		Belgium	3000
18	Site DE49006	Essen	Nordrhein-Westfalen	Germany	45147
19	Site DE49001	Munster		Germany	48149
20	Site ES34002	Barcelona		Spain	8035
21	Site ES34003	Madrid		Spain	28009
22	Site ES34001	Madrid		Spain	28041
23	Site GB44004	Cardiff	Glamorgan	United Kingdom	CF14 4XW
24	Site GB44002	Leeds		United Kingdom	LS1 9EX