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Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease (RESPONSE)

Primary Purpose

Chronic Lung Disease of Prematurity, Respiratory Distress Syndrome in Premature Infant, Bronchopulmonary Dysplasia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Recombinant fragment of human surfactant protein D (rfhSP-D)
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lung Disease of Prematurity focused on measuring Preterm Infants, Recombinant Surfactant Protein D

Eligibility Criteria

23 Weeks - 28 Weeks (Child)All SexesDoes not accept healthy volunteers

Participant Inclusion Criteria: Inborn infants born at between 23 weeks and 0 days and <28 weeks and 0 days gestation. Infant must be intubated or planned to be intubated for respiratory distress at time of eligibility check, and this should be done within 12 hours from time of birth. Receiving standard surfactant therapy Clinically stable on mechanical ventilation. Stability is defined at the time of IMP instillation and is defined below. Written informed consent from parents/guardians/person with legal responsibility Definition of stability: Blood gases within the normal range for preterm infants (pH>7.20; paCO2 <60mmHg) Mean blood pressure with or without inotropic support at at least gestational age or above (mmHg) No evidence of a pneumothorax Clinical observations within acceptable range for an infant of that gestational age No stability concerns from the attending neonatologist Participant Exclusion Criteria: Congenital anomalies i.e any major antenatal diagnosed congenital abnormalities such as congenital heart disease, suspected or known chromosomal abnormalities Parents/legal guardians unable to give consent due to learning or other difficulties Infants requiring only CPAP support without the need for surfactant replacement therapy, i.e. without endotracheal intubation Infants born in very poor condition and judged too sick or unstable to be included (high risk of mortality) in an experimental first in human study, for example infants that are requiring maximal intensive care therapy and have findings such as a grade IV intraventricular haemorrhage that is likely to be life limiting. Infants that are born out of the participating site. Participation in any other interventional study (participation in an observational study is permissible).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Recombinant fragment of human surfactant protein D (rfhSP-D) administration

    Arm Description

    This is a single arm trial with administration of rfhSP-D. All participants will be administered rfhSP-D via an endotracheal tube in 1-3 doses in the first 24-48hrs after birth whilst the infant is still intubated and ventilated. A dose escalation design from 1mg/kg to 4mg/kg will be used. Infants are enrolled in cohorts of three, with the first cohort receiving the lowest dose 1mg/kg. Participants are followed up until they are discharged from hospital.

    Outcomes

    Primary Outcome Measures

    Occurence of Dose Limiting Events to assess the safety profile of the IMP (rfhSP-D)
    To assess the safety profile of rfhSP-D across dose levels based on the occurrence of Dose Limiting Events (DLEs) which are events Garde 3 or above on the NAESS scale related to the IMP
    To find recommended Phase 2 Dose of rfhSP-D
    To establish the Recommended Phase 2 Dose (RP2D) of rfhSP-D for preterm infants born at gestational age of 23 weeks to 27 weeks + 6 days.

    Secondary Outcome Measures

    Occurrence of non-dose limiting events, including SAE/AEs
    To establish the safety profile of rfhSP-D across dose levels based on the occurrence of non-DLEs, including SAE/AEs.
    Systemic absorption of rfhSP-D
    To evaluate systemic absorption of rfhSP-D using serial measurements of rfhSP-D in serum and its continued presence in tracheal fluid.
    Effects of rfhSP-D on the cell counts of inflammatory markers
    To determine the effect of rfhSP-D on Inflammatory markers in the lung secretions (eg.cell counts of the following markers: neutrophils, macrophages, MMPs, neutrophil elastase, IL-8,IL-6, IL-1).

    Full Information

    First Posted
    March 24, 2023
    Last Updated
    June 6, 2023
    Sponsor
    University College, London
    Collaborators
    Medical Research Council
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05898633
    Brief Title
    Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease
    Acronym
    RESPONSE
    Official Title
    Phase 1 Safety Trial of Recombinant Surfactant Protein D to Prevent Neonatal Chronic Lung Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2023 (Anticipated)
    Primary Completion Date
    July 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University College, London
    Collaborators
    Medical Research Council

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to identify the safest dose of recombinant surfactant protein D (drug name: rfhSP-D) that can be administered to preterm infants born at less than 28 weeks gestation, and to help identify whether this can prevent the development of neonatal chronic lung disease.
    Detailed Description
    This is a Phase I, dose escalation safety study that aims to identify the recommended phase 2 dose of recombinant fragment of human surfactant protein D (rfhSP-D) (drug name: rfhSP-D) for infants at risk of neonatal chronic lung disease. This study will aim to establish if the administration of rfhSP-D to the lungs of preterm babies, via an endotracheal tube, is safe at the proposed dosage range (1mg/kg - 4mg/kg) and whether this dose results in detectable concentrations in lung secretions or serum. Surfactant protein D (SP-D) is a naturally occurring component of the surfactant system with anti-inflammatory properties. Current surfactant replacement therapy contains phospholipids and surfactant proteins B and C (SP-B and SP-C) but no surfactant protein A (SP-A) or surfactant protein D (SP-D). Proof of concept regarding the anti-infective and anti-inflammatory activity of SP-D has been achieved in mouse and a preterm lamb models of lung disease and supports increasing evidence of the role played by deficiency of SP-D in human respiratory diseases. Subjects will be enrolled in cohorts with increasing dose. Whether or not the dose is escalated will depend on the occurrence of dose limiting events (DLE) in all current patients and the doses that they have received. A model will be used to estimate the risk of DLE per dose level. Initial estimates of these risks will be updated using data collected throughout the trial. Up to 24 infants of less than 28 weeks gestation will be recruited in the study and receive intra-tracheal administration of SP-D59, in the dose range 1mg/kg, 2mg/kg or 4mg/kg per dose for up to 3 doses. The first dose of SP-D59 will be given as soon as possible (within 2 hours) after the first dose of standard surfactant therapy (e.g., Curosurf). Subsequent doses of the IMP will be given at 12 hours and 24 hours after the first dose was administered.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Lung Disease of Prematurity, Respiratory Distress Syndrome in Premature Infant, Bronchopulmonary Dysplasia
    Keywords
    Preterm Infants, Recombinant Surfactant Protein D

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    A Bayesian Continual Reassessment Method (CRM) will be used for the RESPONSE trial to inform how the IMP dose should be adapted for the next cohort based on past trial data. The CRM is a model-based design that uses a statistical model to estimate the risk of dose limiting events (DLE) per dose level. The target level of DLEs is set at 20% The CRM model does not allow dose-skipping. The recommended phase 2 dose in terms of safety (efficacy will also be taken into account) will be the highest dose level that has an estimated probability of DLE closest but below the target DLE level of 20%.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    24 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Recombinant fragment of human surfactant protein D (rfhSP-D) administration
    Arm Type
    Experimental
    Arm Description
    This is a single arm trial with administration of rfhSP-D. All participants will be administered rfhSP-D via an endotracheal tube in 1-3 doses in the first 24-48hrs after birth whilst the infant is still intubated and ventilated. A dose escalation design from 1mg/kg to 4mg/kg will be used. Infants are enrolled in cohorts of three, with the first cohort receiving the lowest dose 1mg/kg. Participants are followed up until they are discharged from hospital.
    Intervention Type
    Drug
    Intervention Name(s)
    Recombinant fragment of human surfactant protein D (rfhSP-D)
    Other Intervention Name(s)
    rfhSP-D
    Intervention Description
    Administration of rfhSP-D
    Primary Outcome Measure Information:
    Title
    Occurence of Dose Limiting Events to assess the safety profile of the IMP (rfhSP-D)
    Description
    To assess the safety profile of rfhSP-D across dose levels based on the occurrence of Dose Limiting Events (DLEs) which are events Garde 3 or above on the NAESS scale related to the IMP
    Time Frame
    Day 0 to 96 hours
    Title
    To find recommended Phase 2 Dose of rfhSP-D
    Description
    To establish the Recommended Phase 2 Dose (RP2D) of rfhSP-D for preterm infants born at gestational age of 23 weeks to 27 weeks + 6 days.
    Time Frame
    Day 0 to the point of hospital discharge (40 weeks post-menstrual age)
    Secondary Outcome Measure Information:
    Title
    Occurrence of non-dose limiting events, including SAE/AEs
    Description
    To establish the safety profile of rfhSP-D across dose levels based on the occurrence of non-DLEs, including SAE/AEs.
    Time Frame
    Day 0 to the point of hospital discharge (40 weeks post-menstrual age)
    Title
    Systemic absorption of rfhSP-D
    Description
    To evaluate systemic absorption of rfhSP-D using serial measurements of rfhSP-D in serum and its continued presence in tracheal fluid.
    Time Frame
    Day 0 to 36 weeks post menstrual age
    Title
    Effects of rfhSP-D on the cell counts of inflammatory markers
    Description
    To determine the effect of rfhSP-D on Inflammatory markers in the lung secretions (eg.cell counts of the following markers: neutrophils, macrophages, MMPs, neutrophil elastase, IL-8,IL-6, IL-1).
    Time Frame
    Day 0 to 36 weeks post menstrual age

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    23 Weeks
    Maximum Age & Unit of Time
    28 Weeks
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Participant Inclusion Criteria: Inborn infants born at between 23 weeks and 0 days and <28 weeks and 0 days gestation. Infant must be intubated or planned to be intubated for respiratory distress at time of eligibility check, and this should be done within 12 hours from time of birth. Receiving standard surfactant therapy Clinically stable on mechanical ventilation. Stability is defined at the time of IMP instillation and is defined below. Written informed consent from parents/guardians/person with legal responsibility Definition of stability: Blood gases within the normal range for preterm infants (pH>7.20; paCO2 <60mmHg) Mean blood pressure with or without inotropic support at at least gestational age or above (mmHg) No evidence of a pneumothorax Clinical observations within acceptable range for an infant of that gestational age No stability concerns from the attending neonatologist Participant Exclusion Criteria: Congenital anomalies i.e any major antenatal diagnosed congenital abnormalities such as congenital heart disease, suspected or known chromosomal abnormalities Parents/legal guardians unable to give consent due to learning or other difficulties Infants requiring only CPAP support without the need for surfactant replacement therapy, i.e. without endotracheal intubation Infants born in very poor condition and judged too sick or unstable to be included (high risk of mortality) in an experimental first in human study, for example infants that are requiring maximal intensive care therapy and have findings such as a grade IV intraventricular haemorrhage that is likely to be life limiting. Infants that are born out of the participating site. Participation in any other interventional study (participation in an observational study is permissible).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Trial Manager
    Phone
    020 3108 4255
    Email
    cctu.response@ucl.ac.uk
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Howard Clark, MB
    Organizational Affiliation
    University College London Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    There is currently no plan to make individual participant data available to other researchers. Written requests will be considered by the RESPONSE Trial Management Group.

    Learn more about this trial

    Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease

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