Advanced Imaging for Pulmonary Fibrosis

Recruiting in Palo Alto (17 mi)

Overseen by Sydney Montesi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Peter Caravan

Must be taking: Immunosuppressants

Must not be taking: Anti-fibrotics, Pulmonary vasodilators

Disqualifiers: Emphysema, Pregnancy, MRI contraindications, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if measurements of active collagen deposition using \[68Ga\]CBP8 positron emission tomography (PET) and tissue injury using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict an individual patient's pace of disease progression in non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD) and identify which individuals will develop progressive pulmonary fibrosis.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of certain immunosuppressive medications (like prednisone, mycophenolate mofetil, and/or rituximab) for at least 3 months before joining. If you're on these medications, you won't need to stop them.

What data supports the effectiveness of the treatment 68Ga-CBP8 for pulmonary fibrosis?

Research shows that 68Ga-CBP8, a probe that targets collagen, is effective in detecting and monitoring pulmonary fibrosis in animal models. It has shown high specificity for fibrosis and correlates well with the amount of lung collagen, making it a promising tool for noninvasive imaging of this condition. ^{1 2 3 4 5}

Is the imaging agent used in the trial safe for humans?

The imaging agent 68Ga-CBP8 was tested in nine healthy volunteers and showed no adverse effects, with rapid clearance from the body through the kidneys. Gadoterate meglumine, another agent mentioned, is a contrast agent used in medical imaging and has been assessed for safety in various studies. ^{1 2 6 7 8}

How does the treatment for pulmonary fibrosis using 68Ga-CBP8 differ from other treatments?

The treatment using 68Ga-CBP8 is unique because it involves a noninvasive imaging technique that targets type I collagen, a key component in lung scarring, allowing for early detection and monitoring of pulmonary fibrosis. Unlike traditional treatments that focus on managing symptoms, this approach provides a way to visualize and quantify the extent of fibrosis in the lungs. ^{1 2 3 4 9}

Research Team

Sydney Montesi, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults aged 18-80 with certain types of lung scarring diseases, like chronic hypersensitivity pneumonitis or connective tissue-associated ILD. They must have been on a stable immunosuppression treatment for at least 3 months and diagnosed within the last 5 years. Their lungs should function at a minimum level as measured by specific breathing tests.

Inclusion Criteria

I've been on a steady dose of immunosuppression medication for over 3 months.

I was diagnosed with ILD within the last 5 years.

I am between 18-80 years old with a specific lung condition related to chronic inflammation or connective tissue disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo combined [68Ga]CBP8 PET and DCE-MRI at baseline

1 week

1 visit (in-person)

Monitoring

Participants are monitored for disease progression using pulmonary function tests and imaging

24 months

5 visits (in-person) at 6, 12, 18, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after the main monitoring period

4 weeks

Treatment Details

Interventions

• [68Ga]CBP8 (Imaging Agent)
• Gadoterate Meglumine (Imaging Agent)

Trial Overview The study is testing two advanced imaging techniques: PET scans using [68Ga]CBP8 to measure collagen in the lungs, and DCE-MRI to assess lung injury. The goal is to see if these can predict how fast the disease will progress in patients with non-idiopathic pulmonary fibrosis.

Participant Groups

Group I: Participants with Pulmonary Fibrosis Experimental Treatment 2 Interventions

Participants with non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD) will receive \[68Ga\]CBP8 and undergo PET combined with dynamic contrast-enhanced MRI

Who Is Running the Clinical Trial?

Peter Caravan

Lead Sponsor

Trials

2

Recruited

140+

Findings from Research

The 68Ga-Collagen Binding Probe #8 (68Ga-CBP8) was safely administered to nine healthy volunteers, showing no adverse effects and demonstrating favorable biodistribution with rapid renal clearance.

This probe has potential for noninvasive imaging of tissue fibrosis, with pharmacokinetics indicating a quick initial distribution and a longer elimination phase, making it suitable for assessing fibrotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. Izquierdo-Garcia, D., Désogère, P., Fur, ML., et al.[2023]

The peptide-based PET probe 68Ga-CBP8 specifically targets collagen type I and shows high specificity for pulmonary fibrosis in a mouse model, indicating its potential for noninvasive imaging of this condition.

In vivo and ex vivo studies demonstrated a strong correlation between 68Ga-CBP8 uptake and lung collagen levels, suggesting it could effectively monitor treatment responses in pulmonary fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Désogère, P., Tapias, LF., Hariri, LP., et al.[2018]

The study developed a collagen-targeted PET probe, 64Cu-CBP7, which showed significantly higher uptake in the lungs of mice with bleomycin-induced pulmonary fibrosis compared to healthy controls, indicating its potential for early detection of lung fibrosis.

64Cu-CBP7 demonstrated superior metabolic stability and specificity for collagen, making it a promising candidate for noninvasive imaging of pulmonary fibrosis progression in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. Désogère, P., Tapias, LF., Rietz, TA., et al.[2020]

CBP1495 is a newly identified collagen-binding peptide that effectively targets collagen type I, showing strong binding affinity and potential for use in imaging fibrosis.

The 99mTc-labelled version of CBP1495 demonstrated significant accumulation in fibrotic tissues in rat models, indicating its potential as a non-invasive radiotracer for diagnosing and monitoring fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. Zheng, L., Ding, X., Liu, K., et al.[2018]

CM-101, a new MR probe targeting type I collagen, showed rapid blood clearance and primarily renal elimination in rats, indicating a favorable safety profile with negligible accumulation in bone or other tissues.

The probe effectively quantified liver fibrosis in animal models, with significant increases in contrast-to-noise ratio (ΔCNR) in fibrotic rats and mice, demonstrating its potential as a reliable imaging tool for assessing liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CM-101: Type I Collagen-targeted MR Imaging Probe for Detection of Liver Fibrosis. Farrar, CT., Gale, EM., Kennan, R., et al.[2019]

Gadoterate meglumine (Gd-DOTA) demonstrated a diagnostic efficacy of over 99% in establishing diagnoses during MRI scans in a study involving 24,308 patients across 61 institutions.

The safety profile of Gd-DOTA was favorable, with only 0.4% of patients experiencing adverse events, mostly minor, and only one serious event reported, which resulted in complete recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and diagnostic value of the gadolinium chelate gadoterate meglumine (Gd-DOTA). Herborn, CU., Honold, E., Wolf, M., et al.[2022]

A total of 424 risk signals related to adverse events (AEs) were identified from the FAERS database for four gadolinium-based contrast agents (GBCAs) over an 18-year period, highlighting significant safety concerns associated with these agents.

The study revealed that some adverse events linked to GBCAs were not included in their package inserts, indicating a need for further research to ensure patient safety and awareness of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data mining and analysis of the adverse events derived signals of 4 gadolinium-based contrast agents based on the US Food and drug administration adverse event reporting system. Wang, L., Wang, Y., Zhao, Q.[2023]

The gadolinium-based probe EP-3533 effectively enhances the visibility of endometriotic lesions in MRI scans, demonstrating its potential for non-invasive detection of endometriosis in two murine models.

Unlike the non-binding isomer EP-3612, EP-3533 specifically accumulates in endometriotic lesions, indicating its ability to target collagen type I, which could lead to future therapeutic applications in treating endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis. Talebloo, N., Bernal, MAO., Kenyon, E., et al.[2023]

References

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

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. [2023]

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

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. [2018]

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

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. [2020]

4. Austria pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. [2018]

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

CM-101: Type I Collagen-targeted MR Imaging Probe for Detection of Liver Fibrosis. [2019]

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

Clinical safety and diagnostic value of the gadolinium chelate gadoterate meglumine (Gd-DOTA). [2022]

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

Data mining and analysis of the adverse events derived signals of 4 gadolinium-based contrast agents based on the US Food and drug administration adverse event reporting system. [2023]

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

Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. [2021]