CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome

NCT04104646 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CLI-06563AA1-02
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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

Conditions

Neonatal Opioid Withdrawal Syndrome

Outcome Measures

Primary Outcomes (1)

• Duration of Treatment

  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.

  Up to 10 weeks after first dose

Secondary Outcomes (6)

• Time to First Weaning

  up to 10 weeks after first dose

• Adjunctive Therapy

  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

• Length of Opioid-related Hospital Stay

  up to 10 weeks plus 48 hours

Study Arms (2)

CHF6563

EXPERIMENTAL

Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo

Drug: CHF6563; Drug: Morphine matched placebo

Morphine

ACTIVE COMPARATOR

Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo.

Drug: Morphine; Drug: CHF6563 matched placebo

Interventions

CHF6563 DRUG

Sublingual CHF6563 administration at starting dose of 10 µg/kg q8

CHF6563

Morphine DRUG

Oral morphine administration at starting dose of 0.07 mg/kg q4

Morphine

CHF6563 matched placebo DRUG

Sublingual CHF6563 matched placebo administration

Morphine

Morphine matched placebo DRUG

Oral morphine matched placebo administration

CHF6563

Eligibility Criteria

• Age: Up to 7 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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).
• Proven or suspected early onset neonatal infection which will require more than 48 hours treatment with antibiotics
• Unable to tolerate an oral or sublingual medication
• Need for medications forbidden in this study protocol
• Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
• Participation in another clinical trial of any medicinal product, placebo, experimental medical device or biological substance conducted under the provisions of a protocol on the same therapeutic target. The participation in studies involving diagnostic devices or treatments for conditions other than NOWS and Neonatal abstinence syndrome (NAS) may be permitted following an agreement with the Sponsor. Non-interventional observational studies are allowed

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (2)

Clinical site 015

Las Vegas, Nevada, 89102, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19144, United States

Location

MeSH Terms

Interventions

Morphine

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

The study objectives could not be addressed because the study was terminated due to a low recruitment; for non-safety reasons. Despite concerted efforts by the Sponsor to improve the enrolment rate (e.g., through communications with the Investigators, changing the training modalities to meet nurses' requests, and decreasing the sample size), the projected time frame to complete the study was longer than 5 years; this was considered unacceptable for the clinical development programme.

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+ 39 0521 2791

Study Officials

• Walter Kraft

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind, double-dummy
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 26, 2019
• Study Start: December 18, 2020
• Primary Completion: December 13, 2021
• Study Completion: December 13, 2021
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)