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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 640
- 试验地点
- 7
- 主要终点
- Phase 2 Primary Endpoint - Overall diagnostic preference
研究概览
简要总结
This is an operationally combined Phase 2/3 study, which will be conducted and evaluated in 2 distinct parts:
- Phase 2: Prospective, adaptive, multicenter, non-randomized, single-blind, dose-finding, including participants with known or highly suspected lesions of the CNS. The aim of the Phase 2 part is to identify an optimized dose of mangaciclanol for the Phase 3 part of the study.
- Phase 3: Prospective, multicenter, randomized, controlled, single-blind, cross-over, including participants with known or highly suspected lesions of the CNS or body. The aim of the Phase 3 part is to further evaluate the efficacy and safety of mangaciclanol-enhanced MRI for the detection and characterization of lesions of the CNS or body.
The investigational medicinal products (IMPs) used during the trial are mangaciclanol and gadobutrol (comparator IMP).
Primary and key secondary efficacy analyses will be based on independent central blinded image evaluation (BIE), and Phase 2 data will be analyzed prior to commencement of Phase 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Phase 3 mangaciclanol-gadobutrol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence mangaciclanol (V2) followed by gadobutrol (V4)
干预措施: Mangaciclanol, also known as GEH200486 Injection, 0.5 mmol/mL (Drug)
Phase 3 gadobutrol-mangaciclanol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence gadobutrol (V2) followed by mangaciclanol (V4)
干预措施: MRI Scan (Diagnostic Test)
Phase 3 gadobutrol-mangaciclanol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence gadobutrol (V2) followed by mangaciclanol (V4)
干预措施: Gadobutrol (Drug)
Phase 2
An initial dose of 0.1 mmol/kg mangaciclanol will be compared to the standard dose of gadobutrol (0.1 mmol/kg) in Cohort 1, in approximately 60 participants.
A second cohort (Cohort 2) may be initiated based on the outcome of the analysis of Cohort 1. This cohort will include approximately 60 participants (higher or lower dose), or 30 participants (same dose), depending on the dose of mangaciclanol selected for further evaluation.
干预措施: Mangaciclanol, also known as GEH200486 Injection, 0.5 mmol/mL (Drug)
Phase 2
An initial dose of 0.1 mmol/kg mangaciclanol will be compared to the standard dose of gadobutrol (0.1 mmol/kg) in Cohort 1, in approximately 60 participants.
A second cohort (Cohort 2) may be initiated based on the outcome of the analysis of Cohort 1. This cohort will include approximately 60 participants (higher or lower dose), or 30 participants (same dose), depending on the dose of mangaciclanol selected for further evaluation.
干预措施: MRI Scan (Diagnostic Test)
Phase 3 mangaciclanol-gadobutrol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence mangaciclanol (V2) followed by gadobutrol (V4)
干预措施: MRI Scan (Diagnostic Test)
Phase 3 gadobutrol-mangaciclanol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence gadobutrol (V2) followed by mangaciclanol (V4)
干预措施: Mangaciclanol, also known as GEH200486 Injection, 0.5 mmol/mL (Drug)
Phase 2
An initial dose of 0.1 mmol/kg mangaciclanol will be compared to the standard dose of gadobutrol (0.1 mmol/kg) in Cohort 1, in approximately 60 participants.
A second cohort (Cohort 2) may be initiated based on the outcome of the analysis of Cohort 1. This cohort will include approximately 60 participants (higher or lower dose), or 30 participants (same dose), depending on the dose of mangaciclanol selected for further evaluation.
干预措施: Gadobutrol (Drug)
Phase 3 mangaciclanol-gadobutrol
Participants with known or highly suspected lesions of CNS or body, randomized to receive treatment sequence mangaciclanol (V2) followed by gadobutrol (V4)
干预措施: Gadobutrol (Drug)
结局指标
主要结局
Phase 2 Primary Endpoint - Overall diagnostic preference
时间窗: 4-47 days
Overall diagnostic preference based on global matched pairs reads according to a 3-point scale that is derived from a 5-point scale (1 = greatly prefer mangaciclanol/prefer mangaciclanol, 0 = no preference, -1 = prefer gadobutrol/greatly prefer gadobutrol), as evaluated by 3 blinded independent readers.
Phase 3 Primary Endpoint - Lesion visualization criteria
时间窗: 4-74 days
Lesion visualization criteria (lesion border delineation, internal morphology and degree of lesion contrast enhancement) for paired (unenhanced plus mangaciclanol-enhanced) MRIs compared to unenhanced MRI based on the primary reads on a 4-point scale (1 = poor / none; 2 = moderate; 3 = good; 4 = excellent) for up to 3 of the most representative lesions.
次要结局
- Phase 3 Secondary Endpoints - Per-lesion specificity(4-74 days)
- Phase 3 Secondary Endpoints - The impact on patient treatment plan(4-74 days)
- Phase 3 Secondary Endpoints - Number and percentage of participants with changes from baseline in serum biochemistry laboratory test results(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in hematology laboratory test results(4-74 days)
- Phase 3 Secondary Endpoints - Intra-reader reproducibility regarding lesion visualization criteria (primary endpoint)(4-74 days)
- Phase 3 Secondary Endpoints - Inter-reader agreement regarding lesion visualization criteria (primary endpoint)(4-74 days)
- Phase 3 Secondary Endpoints - Incidence of participants with at least 1 new lesion detected(4-74 days)
- Phase 2 Secondary Endpoint - Lesion visualization criteria(4-47 days)
- Phase 2 Secondary Endpoint - Number of lesions(4-47 days)
- Phase 2 Secondary Endpoint - Technical adequacy of images for diagnosis(4-47 days)
- Phase 2 Secondary Endpoint - Contrast enhancement percentage (CE%)(4-47 days)
- Phase 2 Secondary Endpoint - contrast-to-noise ratio (CNR)(4-47 days)
- Phase 2 Secondary Endpoint - signal-to-noise ratio (SNR)(4-47 days)
- Phase 2 Secondary Endpoint - Intra-reader reproducibility regarding overall diagnostic preference (primary endpoint).(4-47 days)
- Phase 2 Secondary Endpoint - Inter-reader agreement regarding overall diagnostic preference (primary endpoint).(4-47 days)
- Phase 2 Secondary Endpoint - Incidence of TEAEs(4-47 days)
- Number and percentage of participants with changes from baseline in serum biochemistry laboratory test results(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in hematology laboratory test results(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in urinalysis test results(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in systolic and diastolic blood pressure(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in respiratory rate(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in heart rate(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in temperature(4-47 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in electrocardiogram examinations(4-47 days)
- Phase 3 Secondary Endpoints - Incidence of Treatment Emergent Adverse Events (TEAEs)(4-74 days)
- Phase 2 Secondary Endpoint - Number and percentage of participants with changes from baseline in physical examination findings(4-47 days)
- Phase 2 Secondary Endpoint - Incidence of abnormal safety parameters(4-47 days)
- Phase 3 Secondary Endpoints - Lesion Visualization(4-74 days)
- Phase 3 Secondary Endpoints - Overall diagnostic preference based on global matched pairs reads(4-74 days)
- Phase 3 Secondary Endpoints - Number of lesions(4-74 days)
- Phase 3 Secondary Endpoints - Technical adequacy of images for diagnosis(4-74 days)
- Phase 3 Secondary Endpoints - Patient diagnosis and diagnostic confidence(4-74 days)
- Phase 3 Secondary Endpoints - Contrast enhancement percentage (CE%)(4-74 days)
- Phase 3 Secondary Endpoints - contrast-to-noise ratio (CNR)(4-74 days)
- Phase 3 Secondary Endpoints - signal-to-noise ratio (SNR)(4-74 days)
- Phase 3 Secondary Endpoints - Lesion visualization criteria(4-74 days)
- Phase 3 Secondary Endpoints - Per-lesion sensitivity(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in urinalysis test results(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in systolic and diastolic blood pressure(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in respiratory rate(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in heart rate(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in temperature(4-74 days)
- Phase 3 Secondary Endpoint - Number and percentage of participants with changes from baseline in physical examination findings(4-74 days)
- Phase 3 Secondary Endpoints - Incidence of abnormal safety parameters(4-74 days)