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

NCT05898633 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 18/05642021-001824-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

Preterm Infants; Recombinant Surfactant Protein D

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Occurrence of non-dose limiting events, including SAE/AEs

  Day 0 to the point of hospital discharge (40 weeks post-menstrual age)

• Systemic absorption of rfhSP-D

  Day 0 to 36 weeks post menstrual age

• Effects of rfhSP-D on the cell counts of inflammatory markers

  Day 0 to 36 weeks post menstrual age

Study Arms (1)

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

EXPERIMENTAL

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)

Interventions

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

Administration of rfhSP-D

Also known as: rfhSP-D

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

Eligibility Criteria

• Age: 23 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Inborn infants born at between 23 weeks and 0 days and 29 weeks and 6 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator

Study Sites (1)

University College London Hospitals

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39153779 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Howard Clark, MBBS

  University College London Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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%.

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: June 12, 2023
• Study Start: April 6, 2024
• Primary Completion: November 1, 2025
• Study Completion: December 31, 2025
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)