A Microdose Trial Investigating Binding of [68Ga]Ga-DOTA-CYS-ATH001 in Healthy Subjects and Different Patient Groups.

NCT06562361 | Recruiting Early Phase 1

• 2 other identifiers: INT0082023-506555-15-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

MASH; PSC; Fibrostenotic Crohn's Disease; Healthy Volunteers

Keywords

PET; Tracer; PDGFRB; MASH; PSC; MRI; Crohn´s Disease

Outcome Measures

Primary Outcomes (2)

• [68Ga]Ga-DOTA-Cys-ATH001 uptake in the whole liver of healthy subjects compared with patients with MASH and PSC

  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).

  Assessed during the intervention

• [68Ga]Ga-DOTA-Cys-ATH001 uptake in the GI tract of healthy subjects compared with patients with fibrostenotic CD

  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).

  Assessed during the intervention

Secondary Outcomes (1)

• [68Ga]Ga-DOTA-Cys-ATH001 PET-tracer PK in arterial and venous plasma

  Assessed 5 minutes to 125 minutes post-dose

Other Outcomes (2)

• Whole-body dosimetry of [68Ga]Ga-DOTA-Cys-ATH001 PET tracer in healthy subjects and patients with presumed MASH.

  Assessed during the intervention

• Safety of [68Ga]Ga-DOTA-Cys-ATH001 PET tracer

  Assessed up to 48 hours post intervention

Study Arms (1)

100 µg [68Ga]Ga-DOTA-Cys-ATH001 (target dose of 200 MBq)

EXPERIMENTAL

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.

Drug: [68Ga]Ga-DOTA-Cys-ATH001

Interventions

[68Ga]Ga-DOTA-Cys-ATH001 DRUG

Target dose of 200MBq \[68Ga\]Ga-DOTA-Cys-ATH001 corresponding to a maximum mass dose of 100 µg, administered as an intravenous bolus dose.

100 µg [68Ga]Ga-DOTA-Cys-ATH001 (target dose of 200 MBq)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Male participants must be willing to use condom or be vasectomized or practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the administration of tracer until 3 months after the administration of tracer. Any female partner of a non-vasectomized male participant who is of childbearing potential must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy (see above) from at least 2 weeks prior to administration of tracer to 4 weeks after administration of tracer.
• Cohort 1 (healthy participants)
• Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.
• Cohort 2 (presumed MASH patients) MASH diagnosis based on non-invasive assessments. Participants should have a high level of disease activity with regards to pro-peptide of type III collagen (ProC3) as a marker of ongoing fibrogenesis.
• Steatosis according to biopsy, radiology, or controlled attenuation parameter (CAP) (≥ 280 dB/M 8), assessments ≤ 24 weeks prior to the screening visit.

You may not qualify if:

• 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.
• After 10 minutes of supine rest at the screening visit, any vital signs values outside the following ranges:
• Systolic blood pressure: \< 90 or \>165 mmHg, or
• Diastolic blood pressure \< 50 or \>100 mmHg, or
• Pulse \< 40 or \> 90 bpm
• The participant has a change in body weight ≥5%, 3 months before the screening visit.

Sponsors & Collaborators

• Antaros Medical: lead

Study Sites (3)

CTC Karolinska

Stockholm, SE-171 64 S, Sweden

RECRUITING

CTC Akademiska Uppsala University Hospital, Entrance 85, 2nd level

Uppsala, SE-751 85, Sweden

NOT YET RECRUITING

Section of Gastroenterology/Hepatology, Uppsala University Hospital

Uppsala, SE-751 85, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Johan Vessby

  Section of Gastroenterology/Hepatology SE-751 85 Uppsala, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johan Vessby, MD, PhD

CONTACT

+46 (0)73 356 93 04; johan.vessby@akademiska.se

Study Design

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

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 20, 2024
• Study Start: August 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3)