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

Phase 1 Safety Trial of Recombinant Surfactant Protein D to Prevent Neonatal Chronic Lung Disease

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 30 weeks gestation, and to help identify whether this can prevent the development of neonatal chronic lung disease.

Study Overview

• Status: Completed
• Conditions: Bronchopulmonary Dysplasia; Chronic Lung Disease of Prematurity; Respiratory Distress Syndrome in Premature Infant
• Intervention / Treatment: Drug: Recombinant fragment of human surfactant protein D (rfhSP-D)

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 30 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 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • University College London Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Participant Inclusion Criteria:

1. Inborn infants born at between 23 weeks and 0 days and 29 weeks and 6 days gestation.
2. 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.
3. Receiving standard surfactant therapy
4. Clinically stable on mechanical ventilation. Stability is defined at the time of IMP instillation and is defined below.
5. Written informed consent from parents/guardians/person with legal responsibility

Definition of stability:

1. Blood gases within the normal range for preterm infants (pH>7.20; paCO2 <60mmHg)
2. Mean blood pressure with or without inotropic support at at least gestational age or above (mmHg)
3. No evidence of a pneumothorax
4. Clinical observations within acceptable range for an infant of that gestational age
5. No stability concerns from the attending neonatologist

Participant Exclusion Criteria:

1. Congenital anomalies i.e any major antenatal diagnosed congenital abnormalities such as congenital heart disease, suspected or known chromosomal abnormalities
2. Parents/legal guardians unable to give consent due to learning or other difficulties
3. Infants requiring only CPAP support without the need for surfactant replacement therapy, i.e. without endotracheal intubation
4. 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.
5. Infants that are born out of the participating site.
6. Participation in any other interventional study (participation in an observational study is permissible).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Recombinant fragment of human surfactant protein D (rfhSP-D) administration; 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.

Drug: Recombinant fragment of human surfactant protein D (rfhSP-D); Administration of rfhSP-D; Other Names: rfhSP-D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 0 to 96 hours
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 29 weeks + 6 days.	Day 0 to the point of hospital discharge (40 weeks post-menstrual age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 0 to the point of hospital discharge (40 weeks post-menstrual age)
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.	Day 0 to 36 weeks post menstrual age
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).	Day 0 to 36 weeks post menstrual age

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Medical Research Council
• Investigators: Principal Investigator: Howard Clark, MBBS, University College London Hospital

Publications and helpful links

General Publications

• Bhatt R, Madsen J, Castillo-Hernandez T, Chant K, Dehbi HM, Marlow N, Clark H. Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit. BMJ Open. 2024 Aug 17;14(8):e086394. doi: 10.1136/bmjopen-2024-086394.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2024
• Primary Completion (Actual): December 5, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Preterm Infants; Recombinant Surfactant Protein D
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bronchopulmonary Dysplasia; Respiratory System Agents; Pulmonary Surfactants; Pulmonary Surfactant-Associated Protein D
• Other Study ID Numbers: 18/0564; 2021-001824-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No