Open-label Study of Inhaled RVT-1601 in Preterm Infants

Study Overview
=================
Brief Summary
-----------------
Preterm birth predisposes infants to greater risk for respiratory morbidities and the need for pulmonary care compared to term infants both in the short-term and long-term. In the short-term, preterm birth is a high risk factor for development of bronchopulmonary dysplasia (BPD), the second most common chronic pediatric respiratory disease after asthma. In the long-term, following discharge from the neonatal intensive care unit (NICU) and the hospital, preterm birth carries a high risk for respiratory morbidities (e.g., wheezing, cough, doctor visits, and hospitalizations for respiratory infections) and resource use, which in turn predisposes infants to the development of lung diseases in childhood and adulthood, including airway hyperresponsiveness, asthma, and chronic obstructive pulmonary disease (COPD). There is a significant unmet need for safe and efficacious approaches in the prevention and treatment of respiratory morbidities of prematurity. The study will be conducted in the neonatal intensive care unit (NICU) in preterm infants to determine safety, tolerability and lung delivery performance of RVT-1601, a new inhalation formulation of cromolyn sodium delivered via the eFlow® Closed System (CS) nebulizer/face mask.

Official Title
-----------------
Open-label Study to Assess the Safety, Tolerability, Feasibility, and Pharmacokinetics of Inhaled RVT-1601 in Preterm Infants at High-risk for Long-term Respiratory Morbidities

Conditions
-----------------
Respiratory Morbidities of Prematurity (RMP)

Intervention / Treatment
-----------------
* Drug: RVT-1601


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Preterm infants between 32 weeks 0 days and 34 weeks 6 days of PMA Born between 24 weeks 0 days and 29 weeks 6 days of estimated GA Requiring minimal or no respiratory support (i.e., supplemental oxygen with <2 liters per minute of nasal cannula flow acceptable) Body weight appropriate for gestational age Written informed consent obtained from at least one of the parents or legal guardians Exclusion Criteria: Requiring invasive or noninvasive respiratory support (e.g., mechanical ventilation, CPAP) Clinically unstable (i.e. unable to maintain SpO2 between 90-95 % , escalating respiratory support in the past 24 hours) Major congenital anomaly (chromosomal, renal, cardiac, hepatic, neurologic or pulmonary malformations) Significant cardiac disorder (i.e., pulmonary hypertension) History of major surgical procedure Any condition that would preclude receiving study drug or performing any study-related procedures Participation in any other investigational drug study History of hypersensitivity or intolerance to cromolyn sodium

Ages Eligible for Study
-----------------
Minimum Age: 32 Months
Maximum Age: 35 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RVT-1601 Low Dose<br>Inhaled RVT-1601 administered once daily over two days via eFlow nebulizer | Drug: RVT-1601<br>* Inhaled RVT-1601 administered once daily over two days<br>|
| Experimental: RVT-1601 Mid Dose<br>Inhaled RVT-1601 administered once daily over two days via eFlow nebulizer | Drug: RVT-1601<br>* Inhaled RVT-1601 administered once daily over two days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in heart rate | Assessment of heart rate (beats/min) | Pre-dose and 15 minutes post-dose | 
| Change in blood pressure | Assessment of systolic and diastolic blood pressure (mmHg) | Pre-dose and 15 minutes post-dose | 
| Change in oxygenation | Assessment of peripheral capillary oxygen saturation (SpO2) | Pre-dose and 15 minutes post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) | Assessment of peak plasma concentration of RVT-1601 | 30 minutes post-dose | 
| Total urine excretion | Assessment of total urine content of RVT-1601 | 8 hours post-dose |