EUCTR2019-003159-12-BE进行中（未招募）1 期
A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of LY3884963 in Patients with Fronto-Temporal Dementia with Progranulin Mutations (FTD-GRN) (PROCLAIM) - PROCLAIM
Prevail Therapeutics, a wholly-owned subsidiary of Eli Lilly and Company0 个研究点目标入组 35 人开始时间: 2021年5月27日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 35
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Men or women aged 30 to 85 years (inclusive), at the time of informed consent.
- •2. Body weight range of =40 kg (88 lb) to =110 kg (242 lb) and a body mass index (BMI) of 18 to 34 kg/m2.
- •3. Has symptomatic FTD, including mild behavioral, cognitive, motor or language impairment per Investigator´s assessment (bvFTD, PPA-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment).
- •4. Score =.5 and =15 on CDR plus NACC FTLD sum of boxes.
- •5. Stable use of background medications at least 8 weeks prior to LY3884963 dosing.
- •6. Carrier of a pathogenic progranulin gene (GRN) mutation confirmed by the central laboratory.
- •*All null mutations including nonsense, frameshift, splice site mutations, and complete or partial gene deletions:
- •a.All previously published pathogenic mutations, with proven functional
- •deleterious effect (selected missense mutations may be included provided they are known to be pathogenic), including any pathogenetic mutation published in 1 of the following GRN mutations databases:
- •National Institutes of Health ClinVar database, Leiden Open Variation Database, and University of Antwerp Alzheimer Disease/Frontotemporal Dementia Mutation database.
- •b.All new mutations with low plasma PGRN level (<70 ng/mL) based on central laboratory measurement.
- •7. Negative screening test for mycobacterium tuberculosis (MTB) or documented negative MTB test within 1 year prior to Screening. Text added.
- •8. Age- and gender-appropriate cancer screenings are up to date and completed per the Investigator's judgment and local standard of care prior to Screening.
- •9. Patient and/or patient's legally authorized representative (LAR) (where applicable by local regulation) has the ability to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations. The patient or LAR may also provide consent for future biomedical research in accordance with their national regulations; however, the patient may still participate in the study without providing consent for future biomedical research.
- •10. Patient has a reliable study partner/informant (e.g., family member or friend) willing and able to participate in the study as a source of information on the patient's health status and cognitive and functional abilities (including providing input into the rating scales). The study partner should have regular contact with the patient (in person or via phone/video communication). The study partner must sign a separate partner informed consent form (ICF) indicating that she/he understands the study requirements and is willing to participate and attend study visits requiring study partner input.
- •11. Women of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with folliclestimulating hormone level in the postmenopausal range at Screening based on the central laboratory's range.
- •12. Men and women of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) must use a highly effective method of contraception consistently and correctly for the duration of the study including the long-term follow-up. Highly effective methods of contraception are those that, alone or in combination, result
排除标准
- •1. Diagnosis of a significant CNS disease other than FTD that may be a cause for the patient’s FTD symptoms or may confound study objectives.
- •2. Brain or cervical spine MRI/magnetic resonance angiography (MRA) imaging indicating clinically significant abnormality, including evidence of prior hemorrhage, infarct >1 cm3 or >3 lacunar infarcts, or a structural or vascular abnormality deemed a contraindication to ICM injection.
- •3. Hypersensitivity or contraindications to corticosteroid, rituximab, and/or sirolimus use (including but not limited to osteoporosis with vertebral fractures within 1 year prior to Screening, poorly controlled diabetes [see Exclusion Criterion 5c], uncontrolled hypertension [see Exclusion Criterion 5f]), and uncontrolled hyperlipidemia or hypercholesterolemia per Investigator's assessment.
- •4. Clinical evidence of peripheral symmetric sensory polyneuropathy (stable sensory mononeuropathies and radiculopathies are not exclusionary).
- •5. Concomitant disease or condition within 6 months of Screening that could interfere with, or treatment of which might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable safety risk to the patient or interfere with the patient's ability to comply with study procedures; including, but not limited to, the following:
- •a. Evidence of clinically significant liver disease
- •b. Unstable autoimmune disease requiring chronic immunosuppression; severely immunocompromised patients
- •c. Poorly controlled/not adequately managed diabetes (Screening hemoglobin A1c [HbA1c] =7%)
- •d. History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening
- •e. Clinically significant 12-lead electrocardiogram (ECG) abnormalities at Screening, as determined by the Investigator
- •f. Uncontrolled hypertension defined as: average of 3 systolic blood pressure [SBP]/diastolic blood pressure [DBP] readings >165/100 mm Hg at Screening, or persistent SBP/DBP readings >180/100 mm Hg within 3 months prior to Screening that, in the opinion of the Investigator, are indicative of chronic uncontrolled hypertension
- •g. History of cancer, including B-cell cancers within 5 years of Screening or current presence of precancer lesions, with the exception of fully excised nonmelanoma skin cancers and fully excised prostate carcinoma in situ that have been stable for at least 6 months
- •h. History or current alcohol or drug abuse within 2 years of Screening
- •i. Any current psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, International Statistical Classification of Diseases and Related Health Problems Tenth Revision, or equivalent, that may interfere with the patient’s ability to perform study procedures and all assessments. NOTE: Psychiatric manifestations of FTD are not exclusionary
- •j. At imminent risk of self-harm, based on clinical interview and responses on the C-SSRS. Patient must be excluded if they report ideation with intent, with or without a plan or method (i.e., positive response to items 4 or 5 on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months
- •k. Any medical disorders that, in the opinion of the Investigator, could interfere with study-related procedures (including safe performance of lumbar puncture (LP) or ICM inject
研究者
相似试验
进行中（未招募）
1 期
A Phase 1/2 Study with Ascending Dose in order to Evaluate the Safety and Effects on Progranulin Levels of investigational product under code LY3884963 in Patients with Fronto-Temporal Dementia with Progranulin Mutations (FTD-GRN) (PROCLAIM)Fronto-Temporal Dementia with Progranulin Mutations (FTD-GRN)MedDRA version: 21.1Level: PTClassification code: 10068968Term: Frontotemporal dementia Class: 100000004852CTIS2022-502942-29-01Prevail Therapeutics Inc.35
进行中（未招募）
1 期
A Phase 1/2 Study of VX-522 in Subjects with Cystic FibrosisCystic FibrosisCTIS2023-504786-23-00Vertex Pharmaceuticals Inc.36
进行中（未招募）
1 期
A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomasInoperable advanced cholangiocarcinomasMedDRA version: 20.0Level: LLTClassification code 10008594Term: Cholangiocarcinoma non-resectableSystem Organ Class: 100000054936EUCTR2012-002888-10-GBPCI Biotech AS68
进行中（未招募）
1 期
A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomasInoperable advanced cholangiocarcinomasMedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864EUCTR2012-002888-10-FRPCI Biotech AS61
进行中（未招募）
1 期
A study to investigate the safety, tolerability and efficacy of PCI/Gemcitabine treatment followed by combination chemotherapy in patients with cholangiocarcinomasInoperable advanced cholangiocarcinomasMedDRA version: 19.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864EUCTR2012-002888-10-LTPCI Biotech AS61