Phase-I Study of Radiolabeled DFH-12 (PulmoBind) for Molecular Imaging of the Pulmonary Circulation

NCT01539889 | Completed Phase 1 DMC

• 1 other identifier: The PulmoBind Safety Trial
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary hypertension (PH) can be the result of various clinical conditions. It may be idiopathic or associated with various cardiovascular and lung disorders. Currently there is no test that can non-invasively detect abnormalities of the pulmonary circulation. There is a growing need for a non-invasive method to detect PH. There currently exists only ne agent approved in Canada for clinical imaging of the pulmonary circulation, 99mTc-labeled macroaggregates. This agent is exclusively used for the diagnosis of physical defects of the circulation due to pulmonary embolus. This agent is larger than small pulmonary vessels, limiting its sensitivity to detect small vascular defects, as well as potential infectious risks since albumin macroaggregates are derived from human albumin. There is need then for new lung tracers that could provide a greater safety profile while enabling functional as well as anatomical imaging of the pulmonary circulation. DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Hence the development of this novel AM derivative, PulmoBind, for molecular imaging of the pulmonary circulation. PulmoBind is labeled with 99mTc, the most commonly used imaging isotope in nuclear medicine.

Conditions

Pulmonary Disease; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• To determine optimal dose of PulmoBind to be administered for lung imaging in humans

  To determine the optimal dose of Pulmobind by evaluating the safety and efficacy in three groups of subjects with 3 different doses of study drug; 5mCi, 10mCi, and 15 mCi.For safety evaluation we will provide pharmacokinetic and biodistribution data following injections of the 3 doses mentioned. Vital signs, hematology and biochemistry will also be captured for each of the doses up to 24 and 48 hours after injections of PulmoBind. Furthermore local and systemic reactions 24 hours and 48 hours after injections of PulmoBind will also be captured.

  48 hours

Study Arms (1)

DFH-12 PulmoBind

EXPERIMENTAL

DFH-12 PulmoBind - 3 doses of; 5mCi for 5 subjects, 10mCifor 5 subjects and 15mCi for 10 subject

Radiation: 99mTC-PulmoBind

Interventions

99mTC-PulmoBind RADIATION

DFH-12 (PulmoBind) is a peptide derived from human adrenomedullin (hAMI-52). Adrenomedullin (AM) is a 52-amino acid peptide produced by many tissues in the body, including the vascular endothelium. 3 radiolabeled doses of PulmoBind will be used in this study (5mCi, 10mCi and 15mCi) 5 healthy subjects per dose for the 5 mci and the 10 mci groups but 10 subjects will be used for the 15 mci group.

DFH-12 PulmoBind

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male or female greater than 18 years of age. Female subjects must be post-menopausal (defined as two years after menstrual cycle)
• within normal range for the following: BP systolic 100-140 mmHg and diastolic 50-90 mmHg;
• HR 60-100 beats per minute;
• oral temperature less than 37.6 degrees Centigrade;
• respiratory rate 12-20 breaths per minute;
• normal lung function tests;
• normal echocardiogram including estimation of pulmonary artery systolic pressure;
• normal chest x-ray; Normal electrocardiogram

You may not qualify if:

• any known chronic or acute medical condition with or without the need for chronic pharmacologic therapy or any condition that may interfere with normal biodistribution of DFH-12. Includes but not limited to:
• lung parenchymal or lung vascular diseases such as chronic obstructive pulmonary disease,
• bronchitis,
• lung cancer,
• pleural effusion,
• emphysema,
• asthma,
• pulmonary fibrosis,
• occupational lung disease,
• pulmonary hypertension (primary or secondary),
• systemic hypertension,
• diabetes,
• cancer,
• kidney disease,
• liver disease,

Sponsors & Collaborators

• Montreal Heart Institute: lead

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Related Publications (2)

• Levac X, Harel F, Finnerty V, Nguyen QT, Letourneau M, Marcil S, Fournier A, Dupuis J. Evaluation of pulmonary perfusion by SPECT imaging using an endothelial cell tracer in supine humans and dogs. EJNMMI Res. 2016 Dec;6(1):43. doi: 10.1186/s13550-016-0198-3. Epub 2016 May 27.

  PMID: 27234509 DERIVED

• Harel F, Levac X, Nguyen QT, Letourneau M, Marcil S, Finnerty V, Cossette M, Fournier A, Dupuis J. Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand. Mol Imaging. 2015;14. doi: 10.2310/7290.2015.00003.

  PMID: 25812438 DERIVED

MeSH Terms

Conditions

Lung Diseases; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jocelyn Dupuis, MD

  Montreal Heart

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2012
• First Posted: February 28, 2012
• Study Start: December 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: January 1, 2013
• Last Updated: October 1, 2014

Record last verified: 2014-09

Locations

CA (1)