AzTrials
AzTrials

Hematological MalignancyPhase 1NCT03241550

A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

A Phase 1 study testing isavuconazonium sulfate - intravenous and isavuconazonium sulfate - oral in people with Hematological Malignancy, run by Astellas Pharma Global Development, Inc. at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 year to 17 years
Conditions the study is for
Hematological Malignancy
What is being tested?
isavuconazonium sulfate - intravenous and isavuconazonium sulfate - oral
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
16 sitesUnited States
Study dates
2 Oct 2017to 5 Jul 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites
  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Ann & Robert H Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University Hospital of Cleveland

    Cleveland, Ohio, 44106

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Mercy Kansas City

    Kansas City, Missouri, 64108

  • Miller Children's Hospital

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • University of Louisville

    Louisville, Kentucky, 40202

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • The Children's Hospital at TriStar Centennial Medical Center

    Nashville, Tennessee, 37203

  • CHOC Children's Hospital of Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Multicenter, Non-comparative Pharmacokinetics and Safety Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients

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.

Being tested
isavuconazonium sulfate - intravenous, isavuconazonium sulfate - oral
Keywords
invasive fungal disease, Cresemba®, Hematological malignancy, isavuconazonium sulfate, ASP9766, isavuconazole, pediatric population
Medical subject headings
Hematologic Neoplasms, Invasive Fungal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • isavuconazonium sulfate - intravenousDrug

    Also called Cresemba®

    IV infusion

  • isavuconazonium sulfate - oralDrug

    Also called Cresemba®

    Oral

Study groups in NCT03241550
Study groupRoleWhat they receive
isavuconazonium sulfate IV cohort 1: 1 to < 6 years of ageExperimentalPatients 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).
Receives: Drug: isavuconazonium sulfate - intravenous
isavuconazonium sulfate IV cohort 2: 6 to < 12 years of ageExperimentalPatients 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).
Receives: Drug: isavuconazonium sulfate - intravenous
isavuconazonium sulfate IV cohort 3: 12 to < 18 years of ageExperimentalPatients 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).
Receives: Drug: isavuconazonium sulfate - intravenous
isavuconazonium sulfate oral cohort 4: 6 to < 12 years of ageExperimentalPatients 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).
Receives: Drug: isavuconazonium sulfate - oral
isavuconazonium sulfate oral cohort 5: 12 to < 18 years of ageExperimentalPatients 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).
Receives: Drug: isavuconazonium sulfate - oral

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state

    Maximum concentration at steady state (Cmax) will be derived from the PK plasma samples collected.

    Measured: Up to 7 days

  2. PK of isavuconazole in plasma: AUCtau

    Area under the concentration time curve from the time of dosing to the start of next dosing interval at multiple dose conditions (AUCtau) will be derived from the PK plasma samples collected.

    Measured: Up to 7 days

  3. PK of isavuconazole in plasma: tmax

    Time of maximum concentration (tmax) will be derived from the PK plasma samples collected.

    Measured: Up to 7 days

  4. PK of isavuconazole in plasma: Ctrough

    Concentration - trough level (Ctrough) will be derived from the PK plasma samples collected.

    Measured: Up to 28 days

  5. PK of isavuconazole in plasma: CL

    Clearance (CL) will be model-derived.

    Measured: Up to 28 days

  6. PK of isavuconazole in plasma: Vss

    Volume of distribution at steady state (Vss) will be model-derived.

    Measured: Up to 28 days

  7. PK of isavuconazole in plasma: AUCss

    Area under the concentration-time curve at steady state (AUCss) will be model-derived.

    Measured: Up to 28 days

  8. PK of isavuconazole in plasma: t 1/2

    Half-life (t1/2) will be model-derived.

    Measured: Up to 28 days

  9. Safety assessed by nature, frequency and severity of Treatment Emergent Adverse Events (TEAEs)

    A TEAE is defined as an Adverse Event (AE) observed after starting administration of the study drug through follow-up. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). Number of patients with TEAE's will be summarized.

    Measured: Up to 58 days

  10. Number of patients with vital sign abnormalities and/or adverse events

    An abnormality identified during a medical test (e.g. vital signs) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.

    Measured: Up to 28 days

  11. Number of patients with laboratory value abnormalities and/or adverse events

    An abnormality identified during a medical test (e.g. laboratory parameter) should be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of study drug; or the abnormality or test value is clinically significant.

    Measured: Up to 28 days

  12. Safety assessed by routine 12- lead electrocardiogram (ECG)

    Standard 12-lead ECG recordings will be used for the purposes of safety assessment. A 12-lead, resting ECG is to be recorded. Patients should remain supine for at least 5 minutes prior to all ECGs being performed. The results (normal, abnormal not clinically significant, abnormal clinically significant) are to be recorded.

    Measured: Up to 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2017
  2. Study start2 Oct 2017
  3. Primary completion5 Jul 2019
  4. Study completion5 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03241550
Sponsor's protocol ID
9766-CL-0046
Status last verified
Nov 2024
First submitted
3 Aug 2017
Last updated
19 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • 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.

    PubMed 34031051

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing isavuconazonium sulfate - intravenous and isavuconazonium sulfate - oral in people with Hematological Malignancy, run by Astellas Pharma Global Development, Inc. at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (PK) of isavuconazole in plasma: Cmax at steady state (time frame: Up to 7 days). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03241550, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in