OHB-607 for Bronchopulmonary Dysplasia

Recruiting at68 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Shire

Disqualifiers: Congenital malformation, Chromosomal abnormality, Neurological disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine to see if it can prevent a serious lung condition in very premature babies. The goal is to see if this new treatment works better at protecting their lungs and reducing the chances of developing chronic lung disease.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to discuss this with the trial organizers or your doctor.

What data supports the effectiveness of the drug OHB-607 for treating bronchopulmonary dysplasia?

Research suggests that the drug, which includes components like rhIGF-1 and IGFBP-3, may help improve lung function and prevent pulmonary hypertension (high blood pressure in the lungs) in models of bronchopulmonary dysplasia. Additionally, mecasermin rinfabate, a similar drug, has been shown to increase growth in children with growth hormone issues, indicating its potential effectiveness in other conditions. ^{1 2 3 4 5}

Is OHB-607 (Mecasermin rinfabate) generally safe for humans?

Mecasermin rinfabate, a combination of IGF-I and its binding protein IGFBP-3, has been used to treat growth disorders and is designed to reduce side effects like low blood sugar (hypoglycemia) seen with unbound IGF-I. It has a longer half-life and fewer reported adverse events compared to unbound IGF-I, suggesting it is generally safe for use in humans. ^{1 2 3 5 6}

What makes the drug OHB-607 unique for treating bronchopulmonary dysplasia?

OHB-607, also known as Mecasermin rinfabate, is unique because it combines insulin-like growth factor (IGF)-I with its binding protein IGFBP-3, which helps prolong the drug's effect and reduce side effects like low blood sugar. This combination may help prevent lung injury and high blood pressure in the lungs, which are issues in bronchopulmonary dysplasia. ^{1 2 3 5 7}

Research Team

Study Director

Principal Investigator

Shire

Eligibility Criteria

This trial is for extremely premature infants born between 23 and 27 weeks of gestation. Parents must consent to the study, which excludes infants with significant neurological disease, major congenital malformations, genetic disorders, or those whose mothers had severe COVID-19 during pregnancy.

Inclusion Criteria

Written informed consents and/or assents must be signed and dated by the participant's parent(s) prior to any study related procedures. The informed consent and any assents for underage parents must be approved by the IRB/IEC (in accordance with local regulations).

Written informed consents and/or assents must be signed and dated by the participant's birth mother prior to providing study-related information related to birth mother medical history, pregnancy and the birth of the participant. The informed consent and any assents for underage birth mothers must be approved by the IRB/IEC (in accordance with local regulations).

Participants must be between 23 weeks and 27 weeks of pregnancy.

Exclusion Criteria

I have a genetic condition identified by my doctor.

My blood sugar is very low even after taking glucose.

Current or planned participation in a clinical study of another investigational study treatment, device, or procedure (participation in non-interventional studies is permitted on a case-by-case basis).

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive continuous IV infusion of OHB-607 from birth up to PMA 29 weeks +6 days

Approximately 30 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurodevelopmental outcomes and mortality rates

24 months

Long-term follow-up

Assessment of neurodevelopmental outcomes and chronic lung disease burden reduction

12 to 24 months

Treatment Details

Interventions

• OHB-607 (Other)
• SHP607 (Other)

Trial Overview The study tests OHB-607's effectiveness in preventing chronic lung disease in extremely premature babies compared to standard care alone. It aims to see if this drug can reduce long-term respiratory issues these infants often face.

Participant Groups

Group I: OHB-607 Experimental Treatment 1 Intervention

Participants will receive continuous IV infusion of OHB-607 through from birth up to PMA 29 weeks +6 days.

Group II: Standard Neonatal Care Active Control 1 Intervention

Standard neonatal care alone will be provided.

Who Is Running the Clinical Trial?

Shire

Lead Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

OHB Neonatology Ltd.

Lead Sponsor

Trials

1

Recruited

340+

Oak Hill Bio Ltd

Lead Sponsor

Trials

2

Recruited

360+

Findings from Research

Mecasermin rinfabate, a combination of IGF-I and its binding protein IGFBP-3, is FDA-approved for treating severe primary IGF deficiency and growth hormone gene deletion, effectively increasing growth velocity in affected children.

This treatment has a longer serum half-life compared to unbound IGF-I, which helps reduce the risk of hypoglycemia, a common adverse effect associated with unbound IGF-I administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mecasermin rinfabate. Kemp, SF.[2017]

Postnatal treatment with recombinant human IGF-1 (rhIGF-1) and binding peptide 3 (BP3) significantly reduced lung injury and pulmonary fibrosis in models of bronchopulmonary dysplasia (BPD) caused by chorioamnionitis and hyperoxia, as evidenced by improved lung function and structure in newborn rats.

The treatment also prevented right ventricular hypertrophy (RVH) and inhibited epithelial-mesenchymal transition (EMT) in airway epithelial cells, suggesting that rhIGF-1/BP3 could be a promising therapeutic strategy for managing BPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism. Qu, S., Shan, L., Chen, X., et al.[2023]

Mecasermin rinfabate (iPLEX) is a once-daily subcutaneous injection that combines rhIGF-I with rhIGFBP-3 to potentially extend the drug's half-life and reduce side effects, showing similar efficacy to rhIGF-I in various conditions like diabetes and growth hormone insensitivity syndrome.

The safety profile of Mecasermin rinfabate appears comparable to that of rhIGF-I, but there is limited data on its pharmacokinetics in humans, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX. Williams, RM., McDonald, A., O'Savage, M., et al.[2019]

Infusing recombinant human IGF-1 bound to IGFBP-3 at a dosage of 1.5 mg/kg/day for 3 days in mechanically ventilated preterm lambs significantly improved pulmonary and cardiovascular outcomes without causing toxicity to vital organs.

This study establishes that maintaining physiological plasma levels of IGF-1 can positively influence lung development and function in preterm infants, suggesting a potential therapeutic approach for preventing bronchopulmonary dysplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia. Albertine, KH., Dahl, MJ., Rebentisch, A., et al.[2023]

Recombinant human insulin-like growth factor (rhIGF-I) can effectively increase growth velocity in children with IGF deficiency, but it has been associated with adverse events like hypoglycemia, especially when unbound.

Mecasermin rinfabate (iPlex), a combination of IGF-I and its binding protein IGFBP-3, shows a longer half-life and fewer adverse events compared to unbound IGF-I, suggesting it may be a safer option for treating growth disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mecasermin rinfabate. Kemp, SF., Fowlkes, JL., Thrailkill, KM.[2019]

The investigational product rhIGF-1/rhIGFBP-3, delivered via continuous intravenous infusion to preterm infants, showed no degradation when mixed with caffeine citrate, indicating it is safe to co-administer with this medication.

However, furosemide was found to be physically incompatible with rhIGF-1/rhIGFBP-3, and mixing it with ampicillin resulted in lower recovery of the rhIGF-1/rhIGFBP-3 components, suggesting caution is needed when administering these medications together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Protein-Specific Analytical Methodologies to Evaluate Compatibility of Recombinant Human (rh)IGF-1/rhIGFBP-3 with Intravenous Medications Co-Administered to Neonates. Salamat-Miller, N., Qu, W., Chadwick, JS., et al.[2022]

In a study involving 5 preterm infants, intravenous administration of rhIGF-I with its binding protein rhIGFBP-3 safely increased serum IGF-I levels, which are crucial for growth and development.

The treatment was well tolerated, with no adverse effects on blood glucose or other physiological safety measures, indicating that this approach could be a promising intervention for improving growth in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. Löfqvist, C., Niklasson, A., Engström, E., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Mecasermin rinfabate. [2017]

2. England pubmed.ncbi.nlm.nih.gov

The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Mecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mecasermin rinfabate. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Development of Protein-Specific Analytical Methodologies to Evaluate Compatibility of Recombinant Human (rh)IGF-1/rhIGFBP-3 with Intravenous Medications Co-Administered to Neonates. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. [2022]