Advanced Imaging for Pulmonary Fibrosis

Overseen By Ceanna Kalaria

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Peter Caravan

Must be taking: Immunosuppressants

Must not be taking: Anti-fibrotics, Pulmonary vasodilators

Disqualifiers: Emphysema, Pregnancy, MRI contraindications, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if certain imaging tests can predict the progression of pulmonary fibrosis, a lung disease with scarring, in individuals without the idiopathic type. It employs two imaging agents: [68Ga]CBP8 (68Ga-Collagen Binding Probe #8) to assess collagen buildup and Gadoterate Meglumine (Dotarem) to evaluate tissue damage. The trial seeks participants with specific lung diseases related to conditions like rheumatoid arthritis, who are on stable immunosuppressant medications, and show signs of fibrosis on a recent lung scan.

As a Phase 2 trial, this research measures the effectiveness of the imaging tests in an initial, smaller group, allowing participants to contribute to significant advancements in understanding 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 prior data suggests that these imaging techniques are safe for patients with pulmonary fibrosis?

Research has shown that the treatment [68Ga]CBP8 has been tested for safety in humans. In these studies, it successfully detected increased collagen in the lungs of patients with pulmonary fibrosis, indicating it works well without causing harm. The available data reports no serious side effects, suggesting it is well-tolerated.

Gadoterate Meglumine, a contrast agent often used in MRI scans, is generally safe and has been used by many people without issues. Most side effects are mild, such as headaches or nausea.

This trial is in Phase 2, meaning researchers are still carefully checking the treatment's safety. This phase indicates the treatment was safe in earlier tests, but more information is needed to be certain. Participants in this trial will help researchers learn more about the safety and effectiveness of these imaging tools. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the imaging techniques using [68Ga]CBP8 and Gadoterate Meglumine because they offer a novel way to evaluate pulmonary fibrosis. Unlike traditional methods that rely heavily on CT scans and lung biopsies, this approach combines PET imaging with dynamic contrast-enhanced MRI to provide a clearer picture of lung tissue changes. This could potentially allow for earlier and more accurate diagnosis and monitoring of the disease, leading to better-tailored treatments for patients.

What evidence suggests that this imaging technique is effective for predicting disease progression in pulmonary fibrosis?

Research shows that the [68Ga]CBP8 PET probe effectively detects collagen buildup in the lungs. Studies have found that this probe identifies higher collagen levels in individuals with idiopathic pulmonary fibrosis compared to healthy individuals. In animal tests, the probe demonstrated increased activity in fibrotic lungs, indicating its effectiveness in tracking collagen. Detecting collagen is crucial because its buildup signals pulmonary fibrosis, and identifying it can help predict disease progression. Although [68Ga]CBP8 does not treat the condition, it serves as a valuable tool for understanding and monitoring it. Participants in this trial with non-idiopathic pulmonary fibrosis interstitial lung disease will receive [68Ga]CBP8 and undergo PET combined with dynamic contrast-enhanced MRI to evaluate its effectiveness in detecting collagen buildup. ^{1 2 3 4 6}

Who Is on the Research Team?

Sydney Montesi, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 was diagnosed with ILD within the last 5 years.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [68Ga]CBP8
• Gadoterate Meglumine

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

An improved collagelin analogue labeled with gallium-68 for PET imaging shows promise for non-invasive and sensitive assessment of fibrosis, achieving a high radiochemical purity of 98% and stable performance for at least 3 hours.

In studies with mice, the new imaging agent demonstrated specific binding to fibrotic liver tissue, correlating well with fibrosis severity, and exhibited a safe dosimetry profile allowing for multiple PET scans per year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. Velikyan, I., Rosenström, U., Rosestedt, M., et al.[2021]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5568793/

Type I collagen-targeted PET probe for pulmonary fibrosis ... Data show significantly higher uptake of 68Ga-CBP8 in lungs of LDBVL animals ... Probe 68Ga-CBP8 allows monitoring of collagen content in human IPF lung samples.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03535545

Preliminary Evaluation of [68Ga]CBP8 in Healthy ... The goal of this study is to investigate the safety of [68Ga]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis. Detailed Description.

3. jnm.snmjournals.org jnm.snmjournals.org/content/64/5/775

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8 In humans, this probe detected increased collagen in the lungs of those with idiopathic pulmonary fibrosis compared with healthy volunteers (9).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10152126/

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga ... In humans, this probe detected increased collagen in the lungs of those with idiopathic pulmonary fibrosis compared with healthy volunteers (9).

5. thno.org thno.org/v15p2092.pdf

Collagen-targeted PET imaging for progressive ... Our results demonstrating an increase in [68Ga]Ga-NODAGA- collagelin lung uptake from D8 to D22 in. BLM-receiving mice are in accordance with ...

6. advances.massgeneral.org advances.massgeneral.org/pulmonary/article.aspx?id=1297

New Molecular Imaging Tool Detects Pulmonary Fibrosis A new molecular imaging tool that recognizes type I collagen. The probe is being used to identify disease activity in pulmonary fibrosis and other conditions.