Inhaled Ciclesonide Study in Preterm Infants

Venkatesh Sampath

Status and phase: Enrolling; Phase 1

Conditions: Bronchopulmonary Dysplasia

Treatments: Drug: Alvesco Inhalant Product

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06589245

STUDY00003195

R21HD116421 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Our overall objective is to conduct a safety study with inhaled ciclesonide to evaluate known glucocorticoids (sGC)-related acute and intermediate toxic effects while measuring for the first time in neonates its systemic absorption and potential bioactivity (i.e. activation of primary target, the GR, in blood cells).

Full description

Preterm infants born before 30 weeks gestation are at increased risk of developing bronchopulmonary dysplasia (BPD), a leading cause of death and long-term pulmonary insufficiency. Both hydrocortisone and synthetic glucocorticoids (sGC) are commonly used to prevent BPD in premature infants. Clinical trials have shown that hydrocortisone targeted to infants with emerging lung disease does not prevent BPD, while inhaled sGC therapy has shown mixed efficacy in clinical trials. Dexamethasone (DEX) has been shown in clinical trials to reduce BPD rates in premature infants but is associated with short term and long-term adverse effects including cerebral palsy. There is an unmet need for efficacious Glucocorticoid (GC) therapy in premature infants to prevent BPD without encumbering serious adverse events. To address this challenge, our group has been investigating ciclesonide (CIC), a sGC pro-drug that in the inhaled form is FDA approved for use in asthma and allergic rhinitis in older children. Our published and ongoing work has shown that DEX and CIC regulate GR transcriptional targets and several genes implicated in lung protective effects in neonatal rats. Remarkably, CIC does not suppress somatic growth nor IGF-1 levels, induce hyperglycemia, or cause neuroanatomical changes in the cerebral cortex of neonatal rats, which are known pathologies caused by DEX in premature infants. Furthermore, ongoing studies reveal that CIC is as efficacious as DEX in preventing lung injury in a hyperoxia-model of experimental BPD. This study tests the hypothesis that CIC will have minimal systemic absorption and a favorable safety profile in premature infants at risk of developing BPD.

The fear of long-term neurological adverse effects has limited optimal use of sGC therapy to prevent BPD. This application is significant as it proposes to repurpose CIC, an existing sGC, for novel therapeutic use in preterm infants to prevent BPD. CIC is already FDA-approved for use in children >5 years for allergic rhinitis and asthma, and can be used on a compassionate basis down to 2 years of age. The investigators believe our study is impactful and translationally relevant as it addresses an unmet need for efficacious GC therapy to prevent BPD in premature infants without encumbering the neurological and somatic adverse effects. Successful testing of our hypothesis will pave the way for a large, multicenter randomized control trial of CIC therapy in premature infants to prevent BPD.

Enrollment: 30 estimated patients

Sex: All

Ages: 8 to 28 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Viable Infants born between 23 0/7 - 29 6/7 gestation
• Requiring invasive (through an endotracheal tube) mechanical ventilation
• Between day of life 8 to 28.

Exclusion criteria

• Infants with congenital anomalies
• Infants with life-threatening illness
• Infants with active Sepsis or necrotizing enterocolitis (NEC)
• Grade IV interventricular hemorrhage
• Hyperglycemia or hypertension at the time of study drug administration

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Ciclesonide

Experimental group

Description:

Eligible infants will be approached by study team. Parents whose infants consent to the study drug will enter the dose-escalation part of the study. Inhaled Alvesco will be administered daily for 14 days at escalating doses 80mcg and 160mcg.

Treatment:

Drug: Alvesco Inhalant Product

Control

No Intervention group

Description:

Eligible infants will be approached by study team. Parents who refuse consent to the study drug will have standard of care. These parents can accept for their infant's de-identified clinical data to be used as part of the control group.