Safety, Tolerability, Kinetics, and Repeatability of the Novel LPA1 PET Ligand 18F-BMS-986327
- Study HIC#:2000026009
- Last Updated:07/15/2021
A study to evaluate Safety,Tolerability, Kinetics, and Repeatability of the Novel Lysophosphatidic Acid Receptor 1 (LPA1) Positron Emission Tomography (PET) Ligand 18F-BMS-986327.
- Age18 years and older
- Start Date10/01/2019
- End Date12/31/2020
Trial Purpose and Description
This is a Phase 1, open-label study in healthy adult participants and participants with IPF to evaluate 18F-BMS-986327, a novel positron-emitting LPA1 binding tracer, for measurement of available LPA1. The study will include up to 20 completed participants across the 3 parts listed below. All participants will undergo PET-CT scanning with 18F BMS 986327. Part 1 will be initiated first; however, individual study parts are not required to be performed sequentially.
Part 1 (Safety Study): 3 to 5 evaluable (defined as having readable PET-CT images) healthy adult participants or participants with IPF will complete a whole-body dynamic PET-CT scan after a bolus intravenous (IV) injection of 18F-BMS-986327 to confirm tracer safety, image acquisition window, determine radiation dosimetry of the administered radiotracer, and assess optimal imaging time. A minimum of 2 healthy participants will complete Part 1 prior to scanning any participants with IPF.
Part 2 (Test-Retest Study): A group of 6 to 10 evaluable healthy adult participants or participants with IPF will complete two PET-CT scans with IV bolus administration of 18F-BMS-986327, separated by at least 24 hours and within 7 days of one another to determine the binding characteristics under test and retest conditions and to assess the repeatability of binding parameters, ie, within-subject variability. At least 3 participants with IPF will complete Part 2. A 1- to 7-day window is highly recommended for the re-test scan, but in the event of unexpected cancellations, the retest scan may occur no later than 4 weeks after the test scan.
Part 3 (Distribution in Participants with IPF): A group of 3 to 5 evaluable participants with IPF will complete a PET-CT scan with a single IV bolus injection of 18F-BMS-986327 to assess tracer whole body biodistribution and signal retention in the lung. Part 3 may be fulfilled by participants with IPF who complete Part 1 or Part 2 of the study.
Eligibility Criteria for Healthy Controls:
- Body weight at least 50kg (110lbs), Body Mass Index (BMI) within 19 to 32 kg/m^2, inclusive
- Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests
- Negative hepatitis panel and negative human immunodeficiency virus (HIV)antibody screens
- Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must use acceptable method(s) of contraception. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is less than 24 hours, contraception should be continued for a period of 30 days after the last dose of investigational product.
- Women must have a negative urine pregnancy test within 24 hours prior to the start of investigational product.
- Women must not be breastfeeding.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men that are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is less than 24 hours, contraception should be continued for a period of 90 days after the last dose of investigational product.
- Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men do not require contraception.
- Any history or presence of clinically significant respiratory, Gastro Intestinal (GI), renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers
- Any acute or chronic condition that, in the opinion of the investigator in consultation with the BMS Medical Monitor, could jeopardize the subject's safety, tolerability, or pharmacokinetics of 18F-BMS-986327."
- Any major surgery within 4 weeks of study drug administration - Existence of a cold, upper respiratory tract infection, or fever within 5 days prior to check-in
- Presence or history of any abnormality or illness that may affect absorption, distribution, metabolism or elimination of the study drug
- Donation of blood or plasma (exclude the screening visit) within 2 months prior to check in through end of synthesis (EOS), inclusive
Eligibility Criteria for Patients WITH IPF:
- Male and female participants aged 40 to 90 years
- Have clinical symptoms consistent with IPF before Screening.
- Have received first diagnosis of IPF less than 6 years before randomization
- Diagnosis to be consistent with IPF, as determined by the Investigator
- Women must be postmenopausal, or premenopausal with at least 1 of the following:
- Documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy
- In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause.
- Participants with severe motor problems that prevent them from lying still for PET imaging procedure
- Participants who do not have adequate venous access for PET tracer injection or insertion of IV line
- History of any significant drug allergy (such as anaphylaxis) or hepatotoxicity
- Participants who have received a therapeutic radiopharmaceutical within 7 days prior to study drug administration in this study
- Participants who have had additional clinical/investigational PET-CT scans (eg, fluorodeoxyglucose-PET) within a duration of ≤ 10 half-lives of the agent prior to injection of 18F-BMS-986327
- Participants who are currently involved in another clinical study
- Donation of blood or plasma (excluding the screening visit) within 2 months prior to the first PET-CT scan day
- Participants who are unable to communicate effectively with the investigator and comply with all study requirements, restrictions, and directions of the clinical staff
- Participants who are unable to medically tolerate the procedures involved in the performance of the PET-CT scans
- Any history of significant bleeding or hemorrhagic tendencies or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, or Xarelto)
- Inability to comply with restrictions: not permitted to consume alcohol-containing beverages from 3 days prior to Day 1 until study discharge. Subjects are not permitted to smoke while residing at the clinical facility.
- Has had an acute exacerbation of IPF within 2 months prior to screening
- Has a history of clinically significant environmental exposure known to cause pulmonary fibrosis
- Has a known explanation for interstitial lung disease, including, but not limited to, radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans, organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer
- Has a clinical diagnosis of any connective tissue disease
- Currently has clinically significant asthma or chronic obstructive pulmonary disease
- Is expected to receive a lung transplant within 1 year from Day 1 or is on a lung transplant waiting list
- Has clinical evidence of active infection
- Has any history of malignancy
- Has a history of end-stage liver disease
- Has a history of end-stage renal disease requiring dialysis
- Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF)
- Any vascular disease that the Investigator feels will affect safety of participant to take part in trial
- Has taken known potent OATP inhibitors (e.g., rifampicin, riponavir, erythromycin) with 4 weeks prior to Screening (list to be provided in full protocol) or during the study
- liver function -abnormal results test
- Has creatinine clearance less than 30 mL/minute
- Has ECG result with a QT interval by Fridericia’s correction (QTcF) of ≥ 500 msec at Screening.
- Uncontrolled hypertension
- Has Raynaud's disease
- Has a history of hormonal- or endocrine-related hypotension or hypertension
- Has a history of severe pulmonary hypertension requiring pharmacologic therapy
- Has a known hypersensitivity to any of the components of study treatment
- Has a history of LPA1 antagonists within 4 weeks of Screening or during the study
- Women who are of childbearing potential or are breastfeeding
- Has smoked cigarettes within 4 weeks of Screening and/or is unwilling to avoid tobacco products throughout the study