A clinical study to assess the efficacy and safety of Leriglitazone in adult male subjects with cerebral Adrenoleukodystrophy.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To evaluate the efficacy of leriglitazone compared to placebo at increasing survival.
研究概览
简要总结
This phase 3, multicenter, randomized, double-blind, placebo-controlled, global clinical study is designed to compare the efficacy and safety of leriglitazone with that of placebo in the treatment of cALD. Approximately 40 male subjects will be enrolled. Subjects must be at least ≥18 years of age with a confirmed genetic diagnosis of X-ALD and diagnosis of cALD, defined as gadolinium-enhancing positive (GdE+) brain lesions, for whom hematopoietic stem cell transplantation is not recommended by the investigator, or the subject is not willing to undergo HSCT. Subjects with adrenomyeloneuropathy (AMN) whose cALD status is unknown could attend a prescreening visit (V-2) for a magnetic resonance imaging (MRI). This MRI should be performed under the specified study conditions and would serve as screening MRI in case the baseline visit is done within 15 days. If the subject does not have a genetic test already available, a blood sample for this purpose will be collected at this prescreening visit. If cALD is confirmed after review of the MRI, then the genetic testing will be performed to confirm eligibility (Inclusion Criteria #3). A separate prescreening informed consent form (ICF) will be provided to and signed by those subjects prior to any assessments being performed. Subjects must have a diagnosis of cALD, genetic confirmation of X-ALD, an MRI severity score (referred to as Loes score) of ≥0.5 and ≤12, and GdE+ brain lesions at Screening. Subjects will not be eligible if they had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (elivaldogene autotemcel [eli-Cel]). As depicted in Figure 1-1, this will be a double-blind placebo-controlled study with a 1:1 randomization, with a primary objective of assessing the efficacy of leriglitazone compared to placebo at increasing survival. The individual subject follow-up is divided into 2 parts: a double-blind part and an open-label extension (OLE). The double-blind part will last for a maximum of 36 months, after which the subject will be allowed to transition to the OLE. Subjects and investigator site personnel will be kept blinded to the initial treatment assignment until the end of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- Male
入选标准
- •Subject is able to read and understand the ICF and has provided written informed consent to participate in the study.
- •Subject is male and aged 18 years.
- •Subject has genetic confirmation of X ALD.
- •Subject has progressive cALD, defined as GdE plus brain lesions.
- •Subjects for whom HSCT is not recommended by the investigator or subject is not willing to undergo HSCT.
- •Subject has a Loes score 0.5 and 12 at Screening.
- •Subject does not have major functional disability in the Major Functional Disabilities Neurological Function Score (MFD-NFS), other than wheelchair bound or total incontinence, which will be allowed as these are considered expected symptoms of AMN in the time course of the disease.
- •Subject does not have major cognitive impairment which would impair his ability to take part in the study as determined by the investigator at screening.
- •Subject has normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.
排除标准
- •Subject who had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (eli-Cel).
- •Subject has known type 1 or type 2 diabetes.
- •Subject has known hypersensitivity or intolerance to pioglitazone or any other thiazolidinedione.
- •Subject is taking or has taken honokiol, pioglitazone, or other thiazolidinediones within 3 months prior to Screening.
- •Subject has a requirement for treatment with a prohibited concomitant medication.
- •Subject has a previous or current history of congestive heart failure.
- •Subject has reduced left-ventricular ejection fraction or other clinically significant cardiac abnormalities on echocardiogram that in the opinion of the investigator could predispose the subject to volume overload or its associated consequences.
- •Subject has moderate or severe hepatic impairment (Child-Pugh classification groups B or C).2
- •Subject with chronic kidney disease (CKD) of stage 3 or higher (according to the Renal Association CKD staging).3
- •Subject has previous or current history of cancer, unless surgically resected and without evidence of recurrence for a minimum of 5 years.
- •Subjects who are not surgically sterilized.
- •If not surgically sterilized, subjects should be willing to use adequate contraception and not donate sperm from the first dose of the study drug until 90 days after the EOT visit.
- •Subject has contraindications for MRI such as having paramagnetic material in the body (e.g., aneurysm clips, pacemakers, intraocular metal, or cochlear implants).
- •Subject with conditions that could modify absorption of the study drug.
- •Subject with current participation in another interventional clinical study or within 1 month prior to Screening.
- •Subject with other medical, neuropsychiatric or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.
结局指标
主要结局
To evaluate the efficacy of leriglitazone compared to placebo at increasing survival.
时间窗: To evaluate the efficacy of leriglitazone compared to placebo in 6 weeks.
次要结局
- To evaluate the efficacy of leriglitazone compared to placebo at slowing radiological(progression.)
研究者
Tarun Pandotra
GLOBAL REGULATORY & CONSUMER INSIGHTS