NCT04104646: NOWSHINE

CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome

Terminated Phase 2 Results posted Last updated 3 August 2023

What this trial tests

Phase 2 trial testing CHF6563 in Neonatal Opioid Withdrawal Syndrome in 7 participants. Terminated before completion.

Timeline

18 December 2020

Primary endpoint
13 December 2021

13 December 2021

Quick facts

Lead sponsor	Chiesi Farmaceutici S.p.A.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	7
Start date	18 December 2020
Primary completion	13 December 2021
Estimated completion	13 December 2021
Sites	2 locations across United States

Drugs / interventions tested

• CHF6563 — full drug profile →
• Morphine
• CHF6563 matched placebo — full drug profile →
• Morphine matched placebo — full drug profile →

Conditions studied

• Neonatal Opioid Withdrawal Syndrome — all drugs for Neonatal Opioid Withdrawal Syndrome →

Sponsor

Chiesi Farmaceutici S.p.A. — full company profile →

Who can join

Under 7 Days, any sex, with Neonatal Opioid Withdrawal Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Duration of Treatment Primary · 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 po

All treated patients

Group	Value	95% CI
CHF6563	157.62	3.8 – 547.7
Morphine	570.85	501.5 – 640.2

Patients who completed the study (With Non Missing Data)

Group	Value	95% CI
CHF6563	547.7	547.7 – 547.7
Morphine	501.5	501.5 – 501.5

Time to First Weaning Secondary · up to 10 weeks after first dose

Record the time to first weaning, defined as the number of hours from first dose of study drug administration until the first dose reduction. 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.

All Treated Patients

Group	Value	95% CI
CHF6563	120.3	120.3 – 120.3
Morphine	56.2	40.4 – 72.0

Patients who completed the study (With Non Missing Data)

Group	Value	95% CI
CHF6563	120.3	120.3 – 120.3
Morphine	72	72 – 72

Adjunctive Therapy Secondary · up to 10 weeks after first dose

Record the requirement for adjunctive drug therapy (phenobarbital) for signs of NOWS, recorded as Yes/No. Overall, 1 subject in the CHF6563 group and zero subjects in the morphine were reported as having received adjunctive drug therapy with phenobarbital. The number of subjects randomised in the study was much lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed. NOWS=Neonatal Opioid Withdrawal Syndrome

Group	Value	95% CI
CHF6563	1
Morphine	0

Requirement for Rescue Doses (CHF6563 or Morphine) Secondary · up to 10 weeks after first dose

Requirement for rescue doses and number of rescue doses administered (CHF6563 or morphine); (yes/no). The number of subjects randomised in the study was lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed.

Requirement for rescue doses -- Yes

Group	Value	95% CI
CHF6563	4
Morphine	2

Requirement for rescue doses -- No

Group	Value	95% CI
CHF6563	1
Morphine	0

Number of Rescue Doses Administered Secondary · up to 10 weeks after first dose

Number of rescue doses administered. 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. At the discretion of the physician, a rescue dose of CHF6563 or morphine could be given during the up-titration phase or during the weaning phases to a neonate who had

All Treated Patients

Group	Value	95% CI
CHF6563	1.6	0 – 4
Morphine	3	1 – 5

Patients who completed the study (With Non Missing Data)

Group	Value	95% CI
CHF6563	4	4 – 4
Morphine	1	1 – 1

Length of Opioid-related Hospital Stay Secondary · up to 10 weeks plus 48 hours

Length of opioid-related hospital stay was defined as number of days from day of birth until 48 hours after the final dose of drug treatment for NOWS. Reported data show the length of opioid-related hospital stay (defined as number of days from day of birth until 48 hours after the final dose of drug treatment for NOWS). 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 wa

All Treated Patients

Group	Value	95% CI
CHF6563	10.64	3.9 – 27.0
Morphine	29.5	26.2 – 32.8

Patients who completed the study (With Non Missing Data)

Group	Value	95% CI
CHF6563	27.0	27.0 – 27.0
Morphine	26.2	26.2 – 26.2

Relapse of NOWS Secondary · up to 6 weeks after last dose

Relapse of NOWS, defined as experiencing recurrence of significant signs of withdrawal . Reported are subjects with experiencing a relapse. The number of subjects randomised in the study was much lower than planned. No imputation of missing or incomplete data was made. No statistical analysis was performed. NOWS=Neonatal Opioid Withdrawal Syndrome

Group	Value	95% CI
CHF6563	1
Morphine	0

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs and serious AEs (SAEs) were collected from the time of informed consent signature or from the neonate's birth through treatment and follow-up (FU) period (48 h after last treatment). Daily phone calls with the primary caregiver was for the first 7 d; weekly phone contact was up to 6 weeks after the final opioid treatment dose. NOWS treatment duration depends on Finnegan Neonatal Abstinence Scoring Tool (FNAST) scores and differs for each neonate; the maximum length of treatment was 10 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CHF6563

Serious: 0/5 (0%)

Deaths: 0/5

Morphine

Serious: 0/2 (0%)

Deaths: 0/2

Other adverse events (11 terms — click to expand)

Reaction	System	CHF6563	Morphine
Vomiting	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Fungal infection	Infections and infestations	—	—
Skin candida	Infections and infestations	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Overdose	Injury, poisoning and procedural complications	—	—
Poor feeding infant	Metabolism and nutrition disorders	—	—
Somnolence	Nervous system disorders	—	—
Hypotonia neonatal	Musculoskeletal and connective tissue disorders	—	—
Infantile vomiting	Gastrointestinal disorders	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—

Data from ClinicalTrials.gov NCT04104646 adverse events section.

Sponsor's own description

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

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Opioid treatment for opioid withdrawal in newborn infants.
   Zankl A, Martin J, Davey JG, Osborn DA. · · 2021 · cited 17× · PMID 34231914 · DOI 10.1002/14651858.cd002059.pub4
2. Neonatal opioid withdrawal syndrome: a review of the science and a look toward the use of buprenorphine for affected infants.
   Devlin LA, Young LW, Kraft WK, Wachman EM, et al · · 2022 · cited 14× · PMID 34556799 · DOI 10.1038/s41372-021-01206-3