Neonatal Opioid Withdrawal SyndromePhase 2NOWSHINENCT04104646
CHF6563 in Babies With Neonatal Opioid Withdrawal Syndrome
A Phase 2 study testing CHF6563 and Morphine in people with Neonatal Opioid Withdrawal Syndrome, run by Chiesi Farmaceutici S.p.A. at 2 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages Up to 7 days
- Conditions the study is for
- Neonatal Opioid Withdrawal Syndrome
- What is being tested?
- CHF6563 and Morphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Dec 2020to 13 Dec 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical site 015
Las Vegas, Nevada, 89102
Thomas Jefferson University
Philadelphia, Pennsylvania, 19144
About this study
Official title: 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
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
Read the 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.
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Being tested
- CHF6563, Morphine, CHF6563 matched placebo, Morphine matched placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHF6563Drug
Sublingual CHF6563 administration at starting dose of 10 µg/kg q8
MorphineDrug
Oral morphine administration at starting dose of 0.07 mg/kg q4
CHF6563 matched placeboDrug
Sublingual CHF6563 matched placebo administration
Morphine matched placeboDrug
Oral morphine matched placebo administration
| Study group | Role | What they receive |
|---|---|---|
| CHF6563 | Experimental | Sublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo Receives: Drug: CHF6563; Drug: Morphine matched placebo |
| Morphine | Active comparator | Oral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo. Receives: Drug: Morphine; Drug: CHF6563 matched placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 10 weeks after first dose
Secondary outcomes (6)
Time to First Weaning
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.
Measured: up to 10 weeks after first dose
Adjunctive Therapy
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
Measured: up to 10 weeks after first dose
Requirement for Rescue Doses (CHF6563 or Morphine)
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.
Measured: up to 10 weeks after first dose
Number of Rescue Doses Administered
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 a single FNAST score ≥12. A rescue dose was not to be administered within 1 hour of the previous dose or 1 hour before the next scheduled dose. Rescue doses were the same as the previous dose.
Measured: up to 10 weeks after first dose
Length of Opioid-related Hospital Stay
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 was possible according to the methods defined in the study protocol and the SAP. No statistical analysis was performed.
Measured: up to 10 weeks plus 48 hours
Relapse of NOWS
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
Measured: up to 6 weeks after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2019
- Study start18 Dec 2020
- Primary completion13 Dec 2021
- Study completion13 Dec 2021
Why it stopped: Low recruitment rate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neonatal Opioid Withdrawal SyndromeStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Walter Kraft, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04104646
- Sponsor's protocol ID
- CLI-06563AA1-02
- Acronym
- NOWSHINE
- Status last verified
- Jul 2023
- First submitted
- 24 Sep 2019
- Last updated
- 3 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04104646
- Acronym / sponsor ID
- NOWSHINE / CLI-06563AA1-02
- Conditions
- Neonatal Opioid Withdrawal Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment rate
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Study start
- 18 Dec 2020 (actual)
- Primary completion
- 13 Dec 2021 (actual)
- Study completion
- 13 Dec 2021 (actual)
- First posted
- 26 Sep 2019 (actual)
- Results
- Posted 3 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CHF6563 | Experimental | Drug: CHF6563, Drug: Morphine matched placeboSublingual dose of CHF6563 and the corresponding oral dose of morphine matched placebo |
| Morphine | Active comparator | Drug: Morphine, Drug: CHF6563 matched placeboOral dose of morphine and the corresponding sublingual dose of CHF6563 matched placebo. |
Who may qualify
- Ages
- Up to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CHF6563Sublingual CHF6563 administration at starting dose of 10 µg/kg q8 | Drug | CHF6563 |
| MorphineOral morphine administration at starting dose of 0.07 mg/kg q4 | Drug | Morphine |
| CHF6563 matched placeboSublingual CHF6563 matched placebo administration | Drug | Morphine |
| Morphine matched placeboOral morphine matched placebo administration | Drug | CHF6563 |
Primary outcome
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.
6 secondary outcomes
Time to First Weaning
Time frame: up to 10 weeks after first dose
Adjunctive Therapy
Time frame: up to 10 weeks after first dose
Requirement for Rescue Doses (CHF6563 or Morphine)
Time frame: up to 10 weeks after first dose
Number of Rescue Doses Administered
Time frame: up to 10 weeks after first dose
Length of Opioid-related Hospital Stay
Time frame: up to 10 weeks plus 48 hours
Relapse of NOWS
Time frame: up to 6 weeks after last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter Kraft principal investigator
Thomas Jefferson University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CHF6563 and Morphine in people with Neonatal Opioid Withdrawal Syndrome, run by Chiesi Farmaceutici S.p.A. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Treatment (time frame: Up to 10 weeks after first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2023.