Lung Stem Cell Transplant for Pulmonary Fibrosis

(HALT-IPF Trial)

Overseen By Jackson Pettee

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Other ILD, Obstructive lung disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Purpose: To demonstrate the safety and efficacy of autologous Lung Spheroid Stem Cells (LSCs) administered by intravenous infusion in patients with idiopathic pulmonary fibrosis Progressive Fibrotic Interstitial Lung Disease. Participants: Patients with Idiopathic Pulmonary Fibrosis (IPF) and Progressive Fibrotic Interstitial Lung Disease Procedures (methods): 24 patients previously diagnosed with idiopathic pulmonary fibrosis or Progressive Fibrotic Interstitial Lung Disease meeting all inclusion/exclusion criteria will be evaluated at baseline. LSCs will be grown from autologous trans-bronchial pulmonary biopsy specimens. The first group, consisting of 6 patients will be randomized after completion of the screening procedures to either a treatment group of 100 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. The second group of 18 patients will be randomized after completion of the screening procedures to either a treatment group of 200 million LSCs administered via intravenous infusion or to a control group (standard care) in a 2:1 LSC to control group ratio. Patients will be randomized using permuted blocks in a 2:1 LSC to control group ratio, providing a distribution of 8:4:12 patients among the control, low dose, and high dose groups, respectively. If the patient is randomized and 100 million LSCs are not achieved, then the patient will be analyzed separately and another patient enrolled. Intravenous infusion of LSCs will take place 4-8 weeks after the pulmonary biopsies are obtained. All patients will be followed up at months 0.5, 1, 3, 6, 9, 12, 18, and 24 after infusion to complete the safety and efficacy assessments listed herein. All patients will receive standard of care for their IPF.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, all patients will continue to receive standard care for their condition, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Autologous Lung Stem Cell Transplant for Pulmonary Fibrosis?

Research shows that lung spheroid cells, a type of lung stem cell, can reduce lung damage and promote healing in animal models of pulmonary fibrosis. These cells have been shown to decrease inflammation and fibrosis (scarring) in the lungs, suggesting potential benefits for treating pulmonary fibrosis in humans. ^{1 2 3 4 5}

Is the Lung Stem Cell Transplant for Pulmonary Fibrosis safe for humans?

Research on lung spheroid cells (LSCs) in animal models shows they are generally safe, as they do not cause significant immune reactions or tumor formation. While human studies are limited, preclinical data suggest LSCs could be a safe option for treating pulmonary fibrosis. ^{1 3 4 5 6}

How is the Autologous Lung Stem Cell Transplant treatment different from other treatments for pulmonary fibrosis?

This treatment uses lung spheroid cells, which are derived from the patient's own lung tissue, to promote lung regeneration. Unlike other treatments that use stem cells from other body parts, these cells are specifically from the lungs and can form structures similar to lung tissue, potentially offering a more targeted and effective approach to healing lung damage. ^{1 2 3 4 7}

Research Team

Leonard Lobo, MD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for adults aged 50-80 with Idiopathic Pulmonary Fibrosis (IPF), able to perform a walking test, and have specific lung function measures. Excluded are those with other significant health issues like chronic heart failure, obstructive lung disease, certain infections or recent hospitalization due to IPF.

Inclusion Criteria

Your lung function test shows that your ability to transfer carbon monoxide is greater than 25% of what is expected.

My lung function tests show I breathe well enough.

My lung condition is confirmed as UIP without other causes.

Exclusion Criteria

My lung function tests have shown improvement over the last year.

I have a health issue that makes it hard for me to do certain physical tests.

I was hospitalized for a sudden worsening of my lung condition within the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusion of Lung Spheroid Stem Cells (LSCs) 4-8 weeks after pulmonary biopsies

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at months 0.5, 1, 3, 6, 9, 12, 18, and 24

Treatment Details

Interventions

• Autologous Lung Stem Cell Transplant

Trial Overview The trial tests the safety and effectiveness of two doses of autologous Lung Spheroid Stem Cells (LSCs) in treating IPF. Patients' own cells will be used to grow LSCs which are then given back via IV infusion. Participants will either receive stem cells or standard care and will be monitored over two years.

Participant Groups

Group I: Low Dose LSCs (cohort 1) n = 4 planned Experimental Treatment 1 Intervention

4-8 weeks following transbronchial biopsy, participants in this arm will receive 100 million Lung Spheroid Stem Cell (LSC) infusion.

Group II: High Dose LSCs (Cohort 2) n = 12 planned Experimental Treatment 1 Intervention

4-8 weeks following transbronchial biopsy, participants in this arm will receive 200 million LSC infusion.

Group III: Usual Care (Cohort 1) n = 2 planned Active Control 1 Intervention

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

Group IV: Usual Care (Cohort 2) n = 6 planned Active Control 1 Intervention

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Findings from Research

A new method to generate therapeutic lung progenitor cells from healthy adult lung tissues has been developed, allowing for the creation of three-dimensional lung spheroids that mimic the natural lung environment and contain a mix of lung stem cells and supporting cells.

In animal models, these lung spheroid cells showed significant therapeutic effects, such as reducing fibrosis and promoting blood vessel formation, outperforming traditional stem cells from adipose tissue, indicating their potential for treating severe lung diseases like pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Henry, E., Cores, J., Hensley, MT., et al.[2018]

Transplanting autologous lung-derived mesenchymal stem cells (LMSCs) into sheep with emphysema showed promising results, as the treatment was well tolerated and led to increased lung tissue mass and perfusion after 4 weeks.

Histological analysis confirmed that the LMSCs contributed to tissue regeneration by increasing cellularity and extracellular matrix content, suggesting that this method could be a potential therapy for lung regeneration in emphysema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Ingenito, EP., Tsai, L., Murthy, S., et al.[2022]

The study demonstrates that allogeneic lung spheroid cells (LSCs) can effectively reduce inflammation and fibrosis in a rat model of pulmonary fibrosis, suggesting their potential as a therapeutic option.

Infusion of allogeneic LSCs was found to preserve lung health without causing significant immune rejection, indicating a promising safety profile for future human applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis. Cores, J., Hensley, MT., Kinlaw, K., et al.[2023]

Lung spheroid cells, derived from fibrotic lungs and delivered via tail-vein injections, demonstrated safety and efficacy in treating pulmonary fibrosis in rat models, with a minimum effective dose identified as 3 × 10^6 human cells.

Histological analysis showed no signs of tumor formation or adverse immunological responses, indicating that lung spheroid cells could be a promising therapeutic option for idiopathic pulmonary fibrosis with potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis. Cores, J., Dinh, PC., Hensley, T., et al.[2021]

Idiopathic pulmonary fibrosis currently has no effective pharmacological treatments to significantly improve survival, with lung transplantation being the only option, offering a 45% 5-year survival rate for advanced cases.

Initial clinical trials using mesenchymal stem cells for treatment have not shown convincing safety, but ongoing studies may help determine the best sources and delivery methods, while using stem cell-derived secretome could provide a safer alternative to direct cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis. Barczyk, M., Schmidt, M., Mattoli, S.[2020]

The AETHER trial, involving 9 patients with mild to moderate idiopathic pulmonary fibrosis (IPF), demonstrated that a single intravenous infusion of human mesenchymal stem cells was safe, with no serious adverse events reported within 60 weeks.

While the treatment did not lead to significant improvements in lung function, as indicated by a 3.0% decline in forced vital capacity (FVC) and a 5.4% decline in lung diffusing capacity, the absence of treatment-related complications suggests potential for further exploration of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. Glassberg, MK., Minkiewicz, J., Toonkel, RL., et al.[2018]

Intratracheal transplantation of alveolar type II-like cells derived from induced pluripotent stem cells significantly reduces pulmonary fibrosis in a rat model, even after fibrosis has already developed.

This treatment improves lung structure and works by inhibiting key fibrotic markers, such as transforming growth factor-β and α-smooth muscle actin, suggesting a potential new therapeutic approach for idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis. Alvarez-Palomo, B., Sanchez-Lopez, LI., Moodley, Y., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. [2018]

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

Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. [2022]

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

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis. [2021]

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

Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis. [2020]

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

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis. [2021]