Collagen-targeted PET Imaging for Early Interstitial Lung Disease

• ClinicalTrials.gov Identifier: NCT05417776
• Recruitment Status: Recruiting
• First Posted: June 14, 2022
• Last Update Posted: January 26, 2024
• Sponsor: Massachusetts General Hospital
• Collaborator: Boehringer Ingelheim
• Information provided by (Responsible Party): Sydney Butler Montesi, Massachusetts General Hospital

Tracking Information

• First Submitted Date: May 31, 2022
• First Posted Date: June 14, 2022
• Last Update Posted Date: January 26, 2024
• Actual Study Start Date: September 28, 2022
• Estimated Primary Completion Date: April 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2022)

Degree of uptake of [68Ga]CBP8 [ Time Frame: 24 months ]

The degree of uptake of [68Ga]CBP8 in the lungs will be compared between groups and associations with disease severity and progression will be determined.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 10, 2022)

• Rate of MRI contrast clearance, Kwashout, in the lungs [ Time Frame: 24 months ]
  Kwashout rates will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined.
• Rate of MRI contrast arrival, Kwashin, in the lungs [ Time Frame: 24 months ]
  Kwashin rates will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined.
• Peak enhancement of MRI contrast in the lungs [ Time Frame: 24 months ]
  Peak enhancement will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Collagen-targeted PET Imaging for Early Interstitial Lung Disease
• Official Title: Collagen-targeted PET Imaging for Early Interstitial Lung Disease
• Brief Summary: The goal of this study is to investigate the ability of [68Ga]CBP8 to detect collagen deposition in early interstitial lung disease.

Detailed Description

[68Ga]CBP8, is a PET imaging probe which selectively binds collagen type I. Collagen deposition is a pivotal event in the development of pulmonary fibrosis. [68Ga]CBP8 binds collagen with high affinity and has excellent pharmacological and pharmacokinetic profiles. [68Ga]CBP8 was shown in a mouse model to be effective for detecting lung fibrosis and response to treatment. In addition, [68Ga]CBP8 can detect increased collagen in the lungs of patients with idiopathic pulmonary fibrosis.

The goals of this study are:

1. To determine whether collagen deposition as assessed by [68Ga]CBP8-PET MRI can detect increased collagen deposition in early interstitial lung disease and
2. if the degree of [68Ga]CBP8 uptake predicts subsequent disease progression.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Interstitial Lung Disease

Intervention

• Drug: [68Ga]CBP8
  An injection of up to 350 MBq of [68Ga]CBP8 will be administered intravenously followed by PET-MRI.
• Drug: Dotarem
  Dotarem will be administered during MRI portion of study.
  Other Name: gadoterate meglumine

Study Arms

• Experimental: Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD)
  Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) will receive [68Ga]CBP8 and undergo PET-MRI.
  Interventions:

  • Drug: [68Ga]CBP8
  • Drug: Dotarem
• Experimental: First degree relatives of a family member with pulmonary fibrosis
  First degree relatives of a family member with pulmonary fibrosis will receive [68Ga]CBP8 and undergo PET-MRI.
  Interventions:

  • Drug: [68Ga]CBP8
  • Drug: Dotarem

Publications *

• Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
• Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 10, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 1, 2024
• Estimated Primary Completion Date: April 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Group 1: First degree relatives of a family member with pulmonary fibrosis (n=8)

• Age greater than 40 years
• Have the ability to give written informed consent
• First degree relative of a family member with pulmonary fibrosis
• No known history of interstitial lung disease
• No tobacco use within the prior 6 months.

Group 2: Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) (n=22)

• Age greater than 40 years
• Have the ability to give written informed consent
• ILAs or early ILD (defined by presence of reticular markings and / or traction bronchiectasis but absence of a definite UIP pattern)
• No tobacco use within the prior 6 months.

Exclusion criteria:

• Electrical implants such as cardiac pacemaker or perfusion pump
• Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing
• Historical eGFR of less than 30 mL/min/1.73 m2
• Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate)
• Claustrophobic reactions
• Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months)
• Unable to lie comfortably on a bed inside the MR-PET
• BMI > 33 (limit of the PET-MRI table)
• Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures)
• Pneumonia or other acute respiratory illness within 6 weeks of study entry
• Parenchymal lung disease except for ILD/ILAs or emphysema
• Acute exacerbation of ILD within the prior 6 months
• VATS within the prior 6 months
• Prior radiation therapy to the thorax
• Known allergy to gadolinium.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sydney B Montesi, MD; 617-724-4030; sbmontesi@partners.org

Contact: Abimbola Akinniyi; 781-513-0207; aakinniyi@mgb.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05417776
• Other Study ID Numbers: 2022P001087
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sydney Butler Montesi, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Boehringer Ingelheim
• Investigators: Not Provided
• PRS Account: Massachusetts General Hospital
• Verification Date: January 2024