A First-In-Human, Microdosing, Clinical Trial to Investigate Binding of the PET Tracer [68Ga]Ga-DOTA-CYS-ATH001 Targeting PDGFRβ in Healthy Subjects as Compared to Patients With MASH, PSC and CD
Overview
- Phase
- Early Phase 1
- Intervention
- [68Ga]Ga-DOTA-Cys-ATH001
- Conditions
- MASH
- Sponsor
- Antaros Medical
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- [68Ga]Ga-DOTA-Cys-ATH001 uptake in the GI tract of healthy subjects compared with patients with fibrostenotic CD
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The goal of this clinical trial is to use positron emission tomography (PET) to evaluate and compare the binding of the novel tracer [68Ga]Ga-DOTA-Cys-ATH001 in the liver and/or gastrointestinal tract between healthy volunteers and different patient groups including patients with metabolically caused steatohepatitis (MASH), patients with fibrostenotic Crohn´s Disease (CD) and patients with primary sclerosing cholangitis (PSC).The study will also assess the safety of a microdose of 68Ga]Ga-DOTA-Cys-ATH001 and how it is distributed in different parts of the body. The main questions the study aims to answer are:
- What does the uptake of the [68Ga]Ga-DOTA-Cys-ATH001 PET-tracer look like in the liver of healthy subjects, and in that of patients with MASH and PSC?
- What does the uptake of the [68Ga]Ga-DOTA-Cys-ATH001 PET-tracer look like in the GI tract of healthy subjects, and that of patients with fibrostenotic CD?
- How much [68Ga]Ga-DOTA-Cys-ATH001 PET-tracer can be found in the blood after injection?
- How is [68Ga]Ga-DOTA-Cys-ATH001 uptake distributed in the body?
- What medical problems do participants have when receiving [68Ga]Ga-DOTA-Cys-ATH001?
Participants will:
Receive one administration of [68Ga]Ga-DOTA-Cys-ATH001, after which examination with PET is performed. Magnetic Resonance Imaging (MRI) is also used in the study to create a detailed picture of the body and its function which will facilitate the interpretation of the results of the PET examination. A subset of participants will have blood samples collected after the tracer administration to assess the blood levels of the tracer over time.
A subset of participants will come back for a second visit where they will receive a second administration of [68Ga]Ga-DOTA-Cys-ATH001, followed by PET and MRI.
A health check-up is performed before dosing, and a safety assessment will be performed after dosing. A remote follow-up visit is performed the day after the dosing visit.
Detailed Description
This is a first-in-human (FIH), phase 0, multi-center, non-randomized trial to investigate \[68Ga\]Ga-DOTA-Cys-ATH001 PET-tracer binding in the liver and in the GI tract in healthy subjects and patients with metabolically caused steatohepatitis (MASH), patients with fibrostenotic Crohn´s Disease (CD) and patients with primary sclerosing cholangitis (PSC), in a total of 5 different cohorts, including a sub-trial to assess test-retest reliability and a sub-trial to assess dosimetry. The allocation of cohorts is: * Cohort 1a (n=3): Healthy volunteers, sub-group dosimetry, * Cohort 1b (n=3): Healthy volunteers, sub-group test/retest, * Cohort 2a (n=3): Presumed MASH patients, sub-group dosimetry, * Cohort 2b (n=3): Presumed MASH patients, sub-group test/retest, * Cohort 3 (n=6): Verified MASH patients, * Cohort 4 (n=6): Fibrostenotic CD patients, * Cohort 5 (n=6): PSC patients. The participants will come for 2 or 3 visits to the trial site. The screening (Visit 1) will include an eligibility check and review of health status. Participants in cohort 2 and cohort 3 will perform a FibroScan® investigation. At Visit 2, participants will come to the trial site for PET/MRI and safety assessments. The participants will receive a single, bolus iv injection of a maximum of 100 µg \[68Ga\]Ga-DOTA-Cys-ATH001 after which participants will be examined by whole-body PET/MRI scans. A sub-group of participants in cohort 1 (cohort 1a, healthy subjects, n=3, the first 3 participants in this cohort) and cohort 2 (cohort 2a, presumed MASH patients, n=3, the first 3 participants in this cohort) will be participating in a sub-trial to calculate the whole-body dosimetry of the tracer. These participants will have one longer PET visit and will be examined by sequential whole-body PET/MRI scans to determine tracer biodistribution and clearance. At Visit 4 (within 6 weeks of Visit 2), participants taking part in the test/retest sub-trial (Cohorts 1b and 2b) will come for a second PET/MRI visit which includes a second administration of \[68Ga\]Ga-DOTA-Cys-ATH001. To determine tracer clearance from blood, venous (1a and b and 2a and b) and arterial (1b and 2b) PK samples will be collected post-dose. No PK samples will be taken from cohorts 3 to 5. Safety assessments will take place after the PET/MRI (vital signs, 12-lead ECG, safety laboratory sampling and injection site reactions). A remote follow-up by telephone (Visit 3) will be performed the day after \[68Ga\]Ga-DOTA-Cys-ATH001 dosing to follow-up on AEs, injection site reactions and concomitant medication.For participants in cohorts 1b and 2b (the test/retest sub-group), a remote follow-up by telephone (Visit 5) will be performed the day after \[68Ga\]Ga-DOTA-Cys-ATH001 dosing to follow-up on AEs, injection site reactions and concomitant medication.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to give written informed consent for participation in the trial and able to comply with all trial procedures and requirements.
- •Male or female participant aged 18 to 75 years, inclusive, at the screening visit.
- •Body mass index (BMI) ≥ 19 and \< 40.0 kg/m2 at the time of the screening visit.
- •Women of childbearing potential (WOCBP) must practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) or must agree to use a highly effective method of contraception with a failure rate of \< 1 % to prevent pregnancy from at least 2 weeks prior to administration of tracer for at least 1 week after the PET imaging examination (or for at least 1 weak after the last PET imaging examination for those participants undergoing test/retest PET imaging). In addition, any male partner of a female participant must, unless he has undergone vasectomy, agree to use a condom during the same time period.
- •The following are considered highly effective methods of contraception:
- •combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal),
- •progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable),
- •intra-uterine device \[IUD\]or intra-uterine hormone-releasing system \[IUS\]) WOCBP must refrain from donating eggs until 3 months after the last tracer administration.
- •WOCBP with an exclusive male partner who has undergone vasectomy may choose not to use contraceptives.
- •Women of non-childbearing potential are pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle-stimulating hormone \[FSH\] \>25 IU/L is confirmatory).
Exclusion Criteria
- •Any contraindication for MRI according to a standard checklist used in clinical practice, including claustrophobia, metallic implants or internal electrical devices (e.g., cochlear implant, nerve stimulator, gastric pacemaker, bladder stimulator, cardiac pacemaker, defibrillator, artificial valves in heart, aneurysm clips or coils, etc.), inability to stay in supine position for 90 minutes, and permanent makeup or tattoos which in the Investigator's opinion might jeopardize the participant's safety or interfere with the imaging assessments.
- •Having worked as a metal worker or welder.
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the screening visit.
- •Any malignancy within the past 12 months before the screening visit, with the exception of successfully treated basal cell carcinoma of the skin or in situ prostate cancer under active surveillance, with no interventions scheduled during the period of trial participation.
- •Any planned major surgery within the duration of the trial participation.
- •Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
- •Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B or C antibodies and/or human immunodeficiency virus (HIV).
- •Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc.).
- •Poor peripheral venous access, as judged by the Investigator.
Arms & Interventions
100 µg [68Ga]Ga-DOTA-Cys-ATH001 (target dose of 200 MBq)
All participants will receive a single, bolus iv injection of up to 100 µg \[68Ga\]Ga-DOTA-Cys-ATH001 (target dose of 200 MBq). At Visit 4, cohort 1b (healthy participants, n=3) and cohort 2b (presumed MASH participants, n=3) will come for a second PET/MR imaging visit within 6 weeks from the first imaging visit where an additional bolus iv injection of up to 100 µg \[68Ga\]Ga-DOTA-Cys-ATH001 will be administered.
Intervention: [68Ga]Ga-DOTA-Cys-ATH001
Outcomes
Primary Outcomes
[68Ga]Ga-DOTA-Cys-ATH001 uptake in the GI tract of healthy subjects compared with patients with fibrostenotic CD
Time Frame: Assessed during the intervention
Difference in \[68Ga\]Ga-DOTA-Cys-ATH001 SUV in the GI tract of healthy subjects (cohort 1) compared with patients with fibrostenotic CD (cohort 4).
[68Ga]Ga-DOTA-Cys-ATH001 uptake in the whole liver of healthy subjects compared with patients with MASH and PSC
Time Frame: Assessed during the intervention
Difference in \[68Ga\]Ga-DOTA-Cys-ATH001 mean standardized uptake value (SUV) in the whole liver of healthy subjects (cohort 1), compared with patients with MASH (cohort 2 and 3) and PSC patients (cohort 5).
Secondary Outcomes
- [68Ga]Ga-DOTA-Cys-ATH001 PET-tracer PK in arterial and venous plasma(Assessed 5 minutes to 125 minutes post-dose)