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

• ClinicalTrials.gov Identifier: NCT03816176
• Recruitment Status: Completed
• First Posted: January 25, 2019
• Last Update Posted: January 17, 2023
• Sponsor: Astellas Pharma Global Development, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information

• First Submitted Date: January 23, 2019
• First Posted Date: January 25, 2019
• Last Update Posted Date: January 17, 2023
• Actual Study Start Date: August 22, 2019
• Actual Primary Completion Date: December 14, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2019)

• Safety assessed by Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: Up to 84 days ]
  Number of participants with potentially clinically significant vital sign values
• Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: 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) [ Time Frame: Up to 84 days ]
  Number of participants with potentially clinically significant laboratory values
• All-cause mortality through Day 42 [ Time Frame: Up to 42 days ]
  Each participant will be classified as either a death or alive

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2019)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants
• 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
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability, and efficacy of isavuconazonium sulfate in pediatric participants.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Invasive Mucormycosis
• Invasive Aspergillosis

Intervention

• Drug: Isavuconazonium sulfate
  Intravenous (IV) infusion
  Other Name: Cresemba
• Drug: Isavuconazonium sulfate
  Oral capsule
  Other Name: Cresemba

Study Arms

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

Interventions:

• Drug: Isavuconazonium sulfate
• Drug: Isavuconazonium sulfate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2022): 31
• Original Estimated Enrollment (submitted: January 23, 2019): 30
• Actual Study Completion Date: December 14, 2022
• Actual Primary Completion Date: December 14, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
  • 2. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Spain, United States
• Removed Location Countries: Germany, United Kingdom

Administrative Information

• NCT Number: NCT03816176
• Other Study ID Numbers: 9766-CL-0107; 2018-003975-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

• Current Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Astellas Pharma Global Development, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Executive Director; Astellas Pharma Global Development, Inc.

• PRS Account: Astellas Pharma Inc
• Verification Date: January 2023