2023-509444-10-00招募中1/2 期
A Phase 1/2 Open-Label, Ascending Dose, Multicentre Study to Evaluate the Safety and Preliminary Efficacy of AVB-101 Administered by Bilateral Intrathalamic Infusion in Subjects With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
相关药物
试验速览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 12
- 主要终点
- 1.1. Over a 26-week initial and 5-year total follow-up period: - Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities;
研究概览
简要总结
To evaluate the safety and tolerability of a one-time, intrathalamic administration of AVB-101 in subjects with FTD-GRN.
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Are male or female, 30 to 75 years of age, inclusive, at Screening
- •Have an identified, informed study partner who is able and willing to support the subject’s participation in the study and to provide assessments of the subject during the study (separate, written informed consent to be obtained from the study partner for their participation, where required to do so by the relevant country’s competent authorities).
- •Are carriers of a pathogenic granulin (GRN) mutation (ie, heterozygous loss-of-function mutation causative of FTD) as confirmed by a Sponsor approved genetic test.
- •Have frontotemporal dementia (FTD) as evidenced by Clinical Dementia Rating (CDR) + National Alzheimer’s Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD) global score of 0.5, 1.0, or 2.0
- •Have presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or primary progressive aphasia
- •For women of childbearing potential, must have a negative serum pregnancy test at Screening, a negative urine dipstick, and not be breastfeeding within 2 weeks prior to treatment
- •Are willing to practice a highly effective birth control method as outlined in the Protocol if the subject or partner is of childbearing potential
- •Able and willing to comply with all procedures and the study visit schedule as outlined in the Protocol
- •Able and willing to give written informed consent prior to study participation, and agree to designate a legal representative to act on their wishes to continue participation should they lose capacity to consent at some point during the study OR If, in the Investigator’s opinion, the subject lacks capacity to consent, written informed consent of their legal representative must be obtained in accordance with local laws, regulations, and/or customs. In countries where local laws, regulations, and/or customs do not permit subjects who lack capacity to consent to participate in this study, these subjects will not be enrolled
排除标准
- •Have a classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant”
- •Have the presence of an implanted deep brain stimulation device, ventriculoperitoneal or other cerebrospinal fluid (CSF) shunt, or other implanted device
- •Have severe dementia, defined as CDR + NACC FTLD global score of 3.0, or other symptoms that preclude the ability to comply with study procedures and/or pose unacceptable safety risk to the subject
- •Have evidence of suicide risk, as assessed by the Columbia-Suicide Severity Rating Scale, defined as either a suicide attempt within 6 months prior to Screening or have a significant risk of suicide as judged by the Investigator
- •Have a known or suspected intolerance or hypersensitivity to the study drug or any of the stated ingredients.
- •Have any concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency
- •Have a clinically significant abnormality on magnetic resonance imaging (MRI) at Screening considered to be a contraindication to intrathalamic infusion
- •Have a surgically significant pattern of brain atrophy on MRI at Screening that in the determination of the neurosurgeon interferes with planned neurosurgical trajectory
- •Have had previous treatment with any gene or cell therapy
- •Have had previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment
- •Have had a concomitant disease, any clinically significant laboratory abnormality, or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the subject or interfere with study conduct or the subject's ability to comply with study procedures
- •Have any contraindications to MRI as per local guidelines
- •Have a malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- •Have any contraindications to gadolinium-based contrast agents per local guidelines
- •Have any contraindications to general anesthesia for a period of up to 10 hours and/or cardiopulmonary disorders that would result in higher American Society of Anesthesiology risk classification
- •Have any contraindications to lumbar puncture as per local guidelines
- •Have been hospitalized for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned procedure during the study
- •Are using anticoagulants at Screening, or will have an anticipated need during the period of treatment. Antiplatelet therapies are acceptable concomitant medications if they can be stopped at least 48 hours prior to treatment
- •Have a positive drug screen for drugs of abuse
- •Have a history of substance abuse disorder
结局指标
主要结局
1.1. Over a 26-week initial and 5-year total follow-up period: - Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities;
1.1. Over a 26-week initial and 5-year total follow-up period: - Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities;
1.2. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in vital signs, ECG parameters, and physical and neurological examinations
1.2. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in vital signs, ECG parameters, and physical and neurological examinations
1.3. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in the MMSE;
1.3. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in the MMSE;
1.4. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in biochemistry and hematology safety laboratory tests
1.4. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in biochemistry and hematology safety laboratory tests
1.5. Over a 26-week initial and 5-year total follow-up period: - Incidence of treatment-emergent suicidal ideation or behavior as measured on the C-SSRS;
1.5. Over a 26-week initial and 5-year total follow-up period: - Incidence of treatment-emergent suicidal ideation or behavior as measured on the C-SSRS;
1.6. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in MRI results including edema, inflammation, asymptomatic/symptomatic hemorrhage, and other structural changes.
1.6. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in MRI results including edema, inflammation, asymptomatic/symptomatic hemorrhage, and other structural changes.
次要结局
- 1.1. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in PGRN protein levels in CSF and blood.
- 1.2. Over a 5-year follow-up period: - Change from baseline in CDR + NACC FTLD-SB score; and - Change in CGI-C, PGI-C, and CaGI-C
研究者
Technical Operations
Scientific
Aviadobio Limited
研究点 (12)
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