A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

NCT ID: NCT03241550

Last Updated: 2024-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-02
• Study Completion Date: 2019-07-05

Brief Summary

The purpose of the study is to evaluate the pharmacokinetics (PK), safety and tolerability of multiple doses of intravenous (IV) and oral isavuconazonium sulfate administered daily in pediatric patients. The PK data will be utilized to establish a pediatric population PK model of isavuconazole, the active moiety of isavuconazonium sulfate.

Conditions

Hematological Malignancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

isavuconazonium sulfate IV cohort 1: 1 to < 6 years of age

Patients will receive an intravenous (IV) loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Group Type: EXPERIMENTAL

isavuconazonium sulfate - intravenous

Intervention Type: DRUG

IV infusion

isavuconazonium sulfate IV cohort 2: 6 to < 12 years of age

Patients will receive an IV loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Group Type: EXPERIMENTAL

isavuconazonium sulfate - intravenous

Intervention Type: DRUG

IV infusion

isavuconazonium sulfate IV cohort 3: 12 to < 18 years of age

Patients will receive an IV loading regimen of isavuconazonium sulfate, which consists of a dose every 8 hours (+/- 2 hours) on days 1 and 2, followed by once daily IV maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Group Type: EXPERIMENTAL

isavuconazonium sulfate - intravenous

Intervention Type: DRUG

IV infusion

isavuconazonium sulfate oral cohort 4: 6 to < 12 years of age

Patients will receive a loading regimen of isavuconazonium sulfate by oral administration, comprising one dose every 8 hours (+/- 2 hours) on days 1 and 2 (a total of six doses), followed by once daily oral maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Group Type: EXPERIMENTAL

isavuconazonium sulfate - oral

Intervention Type: DRUG

Oral

isavuconazonium sulfate oral cohort 5: 12 to < 18 years of age

Patients will receive a loading regimen of isavuconazonium sulfate by oral administration, comprising one dose every 8 hours (+/- 2 hours) on days 1 and 2 (a total of six doses), followed by once daily oral maintenance dosing for up to 26 additional days (for a maximum of 28 days of dosing).

Group Type: EXPERIMENTAL

isavuconazonium sulfate - oral

Intervention Type: DRUG

Oral

Interventions

isavuconazonium sulfate - intravenous

IV infusion

Intervention Type: DRUG

isavuconazonium sulfate - oral

Oral

Intervention Type: DRUG

Other Intervention Names

Cresemba®; Cresemba®

Eligibility Criteria

Inclusion Criteria

• Subject has sufficient venous access to permit administration of study drug (for the IV cohorts), collection of pharmacokinetic samples and monitoring of safety laboratories.
• Female subject must either:

• Be of non-childbearing potential: Clearly premenarchal or documented surgically sterile
• Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration; and have a negative urine or serum pregnancy test at screening; and, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least one of which must be a barrier method) starting at screening and throughout the study and for 28 days after the final study drug administration.
• Female subject who is of childbearing potential must agree not to breastfeed starting at screening and throughout the study and for 28 days after the final study drug administration.
• Female subject who is of childbearing potential must not donate ova starting at screening and throughout the study and for 28 days after the final study drug administration.
• Male subject who is of childbearing potential and their female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at screening and continue throughout the study, and for 90 days after the final study drug administration.
• Male subject who is of childbearing potential must not donate sperm starting at screening and throughout the study and, for 90 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.
• For oral cohorts: subject is able to swallow the oral capsule medication.

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 electrocardiogram (ECG).
• Subject has evidence of hepatic dysfunction defined as:

• Total bilirubin ≥ 3 times the upper limit of normal (ULN)
• Alanine transaminase or aspartate transaminase ≥ 5 times the ULN
• Known cirrhosis or chronic hepatic failure
• Subject has used strong cytochrome P450 (CYP) 3A4 inhibitors or inducers such as ketoconazole, rifampin/rifampicin, long acting barbiturates, carbamazepine and St. John's wort in the 5 days prior to the first administration of study drug.
• Subject has known history of allergy, hypersensitivity, or any serious reaction to any of the azole class antifungals.
• Subject has any condition which makes the subject unsuitable for study participation.
• Subject is unlikely to survive 30 days.
• Subject has received investigational therapy, with the exception of oncology drug trials, within 28 days or 5 half-lives, whichever is longer, prior to screening.
• For oral cohorts: The subject has gastrointestinal disease or has had a procedure that is expected to interfere with the oral absorption or tolerance of the study drug (e.g., functionally relevant gastrointestinal obstruction, mucositis/stomatitis, or frequent vomiting).
• Subject previously dosed with isavuconazonium sulfate.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Basilea Pharmaceutica International Ltd

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senior Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Miller Children's Hospital

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

CHOC Children's Hospital of Orange County

Orange, California, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Kansas City

Kansas City, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

University Hospital of Cleveland

Cleveland, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

The Children's Hospital at TriStar Centennial Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Countries

United States

References

Arrieta AC, Neely M, Day JC, Rheingold SR, Sue PK, Muller WJ, Danziger-Isakov LA, Chu J, Yildirim I, McComsey GA, Frangoul HA, Chen TK, Statler VA, Steinbach WJ, Yin DE, Hamed K, Jones ME, Lademacher C, Desai A, Micklus K, Phillips DL, Kovanda LL, Walsh TJ. Safety, Tolerability, and Population Pharmacokinetics of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients. Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0029021. doi: 10.1128/AAC.00290-21. Epub 2021 Jul 16.

Reference Type: DERIVED

PMID: 34031051 (View on PubMed)

Related Links

https://www.clinicaltrials.astellas.com/study/9766-CL-0046/

Link to results and other applicable study documents on the Astellas Clinical Trials website

https://www.trialsummaries.com/Study/StudyDetails?id=25654&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website

Other Identifiers

9766-CL-0046

Identifier Type: -

Identifier Source: org_study_id