A Phase II, Multicenter, Double Blind, Double Dummy, Randomized, 2 Arms Parallel Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome
Overview
- Phase
- Phase 2
- Intervention
- CHF6563
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Sponsor
- Chiesi Farmaceutici S.p.A.
- Enrollment
- 7
- Locations
- 2
- Primary Endpoint
- Duration of Treatment
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
A Phase II, multicenter, double blind, double dummy, randomized, 2 arms parallel study to evaluate the efficacy, safety and pharmacokinetics of CHF6563 in babies with Neonatal Opioid Withdrawal Syndrome
Detailed Description
This was a randomised, multicentre, double-blind, double-dummy, parallel-group, controlled study of CHF6563 (non-ethanolic buprenorphine) sublingual solution. For the enrolled subjects, withdrawal signs were assessed using a pre-defined Finnegan Neonatal Abstinence Scoring Tool (FNAST). FNAST assessments were made in neonates who showed signs of withdrawal despite appropriate non-pharmacological care and were recorded every 4 hours (±1 hour). Pharmacological treatment was to be started up to 7 days after birth in neonates who showed signs of neonatal opioid withdrawal syndrome (NOWS), defined as the sum of three consecutive FNAST scores ≥24 or a single score ≥12, and had failed to respond to non-pharmacological care. After FNAST assessment had started, it was continued for at least 24 hours, even if the baby was not randomised. Sublingual administration of CHF6563 (non-ethanolic buprenorphine) solution (0.075 mg/mL) at a starting dose of 10 μg/kg every 8 hours (q8), using birth weight and oral administration of morphine-matched placebo (sterile water for injection USP), every 4 hours (q4). Thereafter, up-titrations of CHF6563 were possible to a maximum scheduled dose of 90 μg/kg/day. At the discretion of the physician, rescue doses of CHF6563 or morphine could have been given during the treatment to a neonate who had a single score of ≥12. Duration of treatment could last a maximum of 10 weeks. Adverse events (AEs) and serious adverse events (SAEs) were collected starting from the time of informed consent signature or from the neonate's birth (if the informed consent was signed before birth) through treatment and the follow-up period. The study was terminated for non-safety reasons on 04 February 2022, due to low recruitment rate, after only 7 subjects out of a planned 57 subjects had been randomised. An Independent Safety Monitoring Board (ISMB) was in-place to review the safety profile of CHF6563/morphine treatment; the study was terminated before the ISMB reviewed any data.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained by parents/legal representative(according to local regulation) prior to or after birth.
- •Birth weight ≥ 3rd centile for gestational age (GA), according to the Centers for Disease Control and Prevention (CDC) growth chart
- •Gestational age ≥ 36 weeks
- •Exposure to opioids during the last month of fetal life
- •Signs of neonatal opioid withdrawal syndrome requiring treatment, and the sum of 3 consecutive FNAST scores is ≥ 24 or a single score ≥ 12
Exclusion Criteria
- •Familial history of prolonged QTc syndrome
- •Major congenital malformations or evidence of congenital infection
- •Signs of fetal alcohol spectrum disorders
- •Maternal alcohol abuse, defined as average of 3 or more drinks per week in the last 30 days
- •Medical illness at the time of randomization, including but not exclusively:
- •Neonatal hypoglycemia requiring intravenous glucose therapy
- •Neonatal respiratory illness requiring non-invasive or invasive respiratory support
- •Neonatal encephalopathy (including hypoxic ischemic encephalopathy or seizures
- •Severe hyperbilirubinemia-bilirubin at or above the exchange transfusion threshold as defined by the American Academy of Pediatrics (AAP)
- •Severe elevation of serum aminotransferases (more than twice the upper limit of the age appropriate aminotransferases reference range of the investigational site).
Arms & Interventions
CHF6563
Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo
Intervention: CHF6563
CHF6563
Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo
Intervention: Morphine matched placebo
Morphine
Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Intervention: Morphine
Morphine
Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.
Intervention: CHF6563 matched placebo
Outcomes
Primary Outcomes
Duration of Treatment
Time Frame: Up to 10 weeks after first dose
Duration of treatment defined as the number of hours from first dose of study drug administration until the last dose of study drug. Shown are results for the duration of treatment in all treated patients, regardless of discontinuation status, as well as those patients who completed the study (with non missing data). The number of subjects randomised in the study was much lower than planned. Although data from 5 subjects were used in the CHF6563 treatment group, only 2 subjects completed the study as planned i.e. 1 subject in each study arm; no imputation of missing or incomplete data was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed.
Secondary Outcomes
- Relapse of NOWS(up to 6 weeks after last dose)
- Time to First Weaning(up to 10 weeks after first dose)
- Requirement for Rescue Doses (CHF6563 or Morphine)(up to 10 weeks after first dose)
- Number of Rescue Doses Administered(up to 10 weeks after first dose)
- Adjunctive Therapy(up to 10 weeks after first dose)
- Length of Opioid-related Hospital Stay(up to 10 weeks plus 48 hours)