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

NCT ID: NCT05898633

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-06
• Study Completion Date: 2025-12-31

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Administration of rfhSP-D

Interventions

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

Administration of rfhSP-D

Intervention Type: DRUG

Other Intervention Names

rfhSP-D

Eligibility Criteria

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

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).

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 30 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Howard Clark, MBBS

Role: PRINCIPAL_INVESTIGATOR

University College London Hospital

Locations

University College London Hospitals

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39153779 (View on PubMed)

Other Identifiers

2021-001824-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18/0564

Identifier Type: -

Identifier Source: org_study_id