Mangaciclanol for contrast-enhanced MRI to detect and characterize lesions in the brain and body in adults

A Prospective, Multicenter Phase 2/3 Study to Assess the Efficacy and Safety of Mangaciclanol in Adult Patients With Known or Highly Suspected Lesions Referred for Contrast-Enhanced Magnetic Resonance Imaging (MRI) of Central Nervous System (CNS) or Body (LUMINA)

This will test whether the contrast agent mangaciclanol helps MRI scans find and show suspected lesions in the brain or other body parts in adults compared with the standard agent gadobutrol.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 640 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: GE Healthcare (industry)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT07472491 on ClinicalTrials.gov

What this trial studies

This combined Phase 2/3 program first uses a Phase 2, prospective, adaptive, multicenter, non-randomized, single-blind dose-finding stage in adults with known or highly suspected CNS lesions to identify an optimized mangaciclanol dose. The Phase 3 portion is a prospective, multicenter, randomized, controlled, single-blind cross-over comparison of mangaciclanol and gadobutrol in adults with known or suspected enhancing lesions of the CNS or body. Efficacy and key secondary endpoints rely on independent central blinded image evaluation of lesion detection and characterization, with safety monitoring throughout. The investigational product is mangaciclanol (GEH200486) and the active comparator is gadobutrol.

Who should consider this trial

Good fit: Adults who can give informed consent and are referred for contrast-enhanced MRI because they have known or highly suspected enhancing lesions in the CNS or in at least one body region are the intended participants.

Not a fit: People without suspected enhancing lesions, minors, or those with contraindications to manganese- or gadolinium-based contrast agents are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, mangaciclanol could improve lesion visibility on MRI and provide an alternative to gadolinium-based agents for some patients.

How similar studies have performed: Prior small studies of manganese-based MRI agents have shown promise for lesion visualization but large randomized comparisons to gadolinium agents remain limited, so this approach is partly novel.

Eligibility criteria

Inclusion Criteria:

* The participant is of legal majority age, as defined by local laws and regulations at the time of signing the ICF.
* The participant is able and willing to comply with study procedures as described in the protocol.
* The participant has read, understood, signed and dated the ICF prior to any study procedures.
* Phases 2 and 3 CNS: Participants presenting with known or highly suspected enhancing CNS lesions referred as part of standard care for contrast-enhancing MRI of the CNS. The suspicion may be based on a previous imaging procedure such as computed tomography (CT), positron emission tomography (PET)/CT or MRI performed within 12 months prior to ICF signature.
* Phase 3 body only: Participants presenting with known or highly suspected enhancing lesions in at least 1 body region (i.e., head and neck, thorax, abdomen, pelvis, and musculoskeletal system \[only breast in the United States in compliance with local approved indications of gadobutrol\]) referred as part of standard care for contrast-enhancing MRI of the body. The suspicion may be based on a previous imaging procedure such as CT, PET/CT, ultrasound or MRI performed within 12 months prior to ICF signature.
* The participant is scheduled for a contrast-enhanced MRI examination of the CNS or a body region for clinical reasons and has agreed to have a second contrast-enhanced MRI examination for the purpose of this study.
* The participant is in a clinically stable condition (i.e., no acute deterioration within 48 hours before enrollment).
* Female Participants: The participant is a female who is either surgically sterile (has had a documented bilateral oophorectomy, bilateral salpingectomy, and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), or non-lactating, or if of childbearing potential the results of a serum human chorionic gonadotropin pregnancy test, performed at screening and the results of a urine pregnancy test, or serum human chorionic gonadotropin pregnancy test performed prior to each administration of IMP (with the result known before IMP administration), must be negative. Female participants of childbearing potential must agree to use adequate contraception and not harvest or donate eggs from screening until 30 days after final dose of IMP. Such methods include hormonal contraception including oral, intravaginal, transdermal, injectable, and implantable contraceptives; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner. Total abstinence, in accordance with the lifestyle of the participant, is also acceptable.
* Male Participants: The participant is a male who is surgically sterile (vasectomy or bilateral orchidectomy), a male who is sexually active with a partner who is not of childbearing potential, or a male who is sexually active with a partner of childbearing potential who must agree to use adequate contraception and not harvest or donate sperm from screening until 90 days after final dose of IMP. Adequate contraception for the male participant (and any female partner, if she is of childbearing potential) is defined as using hormonal contraception (including oral, intravaginal, transdermal, injectable or implantable contraceptives), an intrauterine device, or an intrauterine hormone-releasing system, combined with at least one of the following forms of contraception: a diaphragm, a cervical cap, or a condom. Total abstinence, in accordance with the lifestyle of the participant, is also acceptable.

Exclusion Criteria:

* The participant has previously enrolled in this mangaciclanol study, including participation in an earlier phase or cohort.
* The participant has a contraindication to MRI examination, such as the presence of a cardiac pacemaker or other electronic devices, presence of ferromagnetic metal foreign bodies in vulnerable positions or within positions that would affect the imaged field of view, presence of certain tattoos that may raise a safety concern for MRI, participant suffering from severe claustrophobia which is not manageable with standard sedation, or participant working as a machinist, welder or metal worker (unless the participant will undergo thorough screening by radiology personnel to rule out the presence of metallic foreign bodies, especially in or near the eyes).
* Participant with severe cardiovascular disease (e.g., known long QT syndrome including QTc prolongation based on screening ECG, acute myocardial infarction within the past 14 days, unstable angina, congestive heart failure class III/IV by New York Heart Association classification, or acute stroke within the past 48 hours).
* (Phase 2 only) Participant with an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) within 14 days prior to the first IMP administration.
* (Phase 3 only) Participant with an eGFR \<30 mL/min/1.73m2 calculated using the CKD-EPI within 14 days prior to the first IMP administration.
* Participant with increased likelihood of hypersensitivity specifically to mangaciclanol, gadolinium or a component of the formulation.
* Participant has received any non-study contrast agent within 72 hours prior to the first study MRI, or is planning to receive any non-study contrast agent during the trial until 24 ± 4 hours after the second study MRI.
* Participant has received any investigational product within 30 days or within 5 times the half-life of that drug, whichever is shorter, prior to or concurrent with this study.
* Participant is expected/scheduled to have any treatment or medical procedure (e.g., chemotherapy, radiotherapy, biopsy, resection, etc.) that may impact aspects of the imaged lesions from the first study MRI up to 24 hours after the second study MRI. (Participants under corticosteroids and/or maintenance chemotherapy with a stable dose at the time of screening visit and throughout the trial can be included).
* Participant may not be able to complete the study, based on their anticipated life expectancy, or where study participation may compromise the management of the participant, or any other reason that in the judgment of the investigator makes the participant unsuitable for participation in the study.
* Participant is pregnant or planning to become pregnant, or breast-feeding.
* Participant is unable or unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and/or considered unlikely to complete the trial.

Where this trial is running

Rochester, Minnesota

• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)

Study contacts

• Study coordinator: Jay Chahal

Conditions: Known or Highly Suspected Central Nervous System Lesion, Known or Highly Suspected Body Lesion, Contrast-enhanced magnetic resonance imaging, Mn-based contrast agents, Gd-based contrast agents, Lesion visualization