A 6 Month, Open-Label, Pilot Futility Clinical Trial of Monthly Young Healthy Male Donor Plasma Transfusions for Progressive Supranuclear Palsy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Number of patients experiencing drug limiting toxicity (DLT)
研究概览
简要总结
This is a phase 1, multi-center, open-label study of the safety, tolerability, pharmacodynamics, and preliminary efficacy of young (<30 years of age) healthy male donor plasma transfusions in patients with PSP. Up to 10 subjects will receive once monthly 4-unit transfusions of young healthy male donor plasma for 6 months.
详细描述
This is a phase 1, multi-center, open-label study of the safety, tolerability, pharmacodynamics, and preliminary efficacy of young (<30 years of age) healthy male donor plasma transfusions in patients with PSP. Up to 10 subjects will receive once monthly 4-unit transfusions of young healthy male donor plasma for 6 months.
If ≥3 subjects experience drug limiting toxicity (DLT), as defined in Section 7.19, the study will be terminated. Any subject that experiences a DLT will be discontinued from further treatment with the study drug.
An interim futility analysis will be performed after five subjects have completed 6 months of study drug treatment. If the criteria listed in Section 9.3 of this protocol are met, an additional 5 subjects will be enrolled in the trial. If not, the trial will be terminated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute of Neurological Disorders and Stroke - Society for Progressive Supranuclear Palsy (NINDS-SPSP) probable or possible PSP criteria (Litvan et al. 1996b), as modified for the AL-108-231 davunetide trial (Boxer et al. 2014);
- •Between 50 and 85 years of age (inclusive);
- •MRI at Screening is consistent with PSP (≤ 4 microhemorrhages and no large strokes or severe white matter disease);
- •MMSE score at Screening is between 14 and 30 (inclusive);
- •Stable medications for 2 months prior to Screening, including Food and Drug Administration- (FDA-) approved Alzheimer's disease (AD) medications and Parkinson's disease medications;
- •Availability of a study partner who knows the subject well and is willing to accompany the subject to all trial visits and to participate in questionnaires;
- •Agrees to 3 MRIs;
- •Agrees to 2 lumbar punctures for CSF examination;
- •Signed and dated written informed consent obtained from the subject and subject's caregiver in accordance with local IRB regulations;
- •Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.
- •Adequate contraceptive methods include those with a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as complete abstinence from sexual intercourse with a potentially fertile partner, and some double barrier methods (condom with spermicide) in conjunction with use by the partner of an intrauterine device (IUD), diaphragm with spermicide, oral contraceptives, birth control patch or vaginal ring, oral, or injectable or implanted contraceptives;
- •For this study, a woman who has been surgically sterilized or who has been in a state of amenorrhea for more than two years will be deemed not to be of childbearing potential.
排除标准
- •Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD (McKhann et al. 2011);
- •Any medical condition other than PSP that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
- •A prominent and sustained response to levodopa therapy;
- •History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
- •History of major psychiatric illness or untreated depression;
- •Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening evaluations;
- •Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
- •Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
- •Current clinically significant viral infection;
- •Major surgery within four weeks prior to Screening;
- •Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening;
- •Any contraindication to monthly plasma transfusions, including but not limited to: a. History of significant transfusion complications; b. Lack of a competent adult in the home to summon medical assistance if needed; c. Lack of a telephone to contact emergency personnel or lack of easy access for emergency vehicles; d. Compatible plasma units not available; e. Prior intolerance to intravenous (IV) fluids; f. IgA deficiency by history or laboratory evidence at Screening; g. Uremia or bleeding; h. Any concurrent use of an anti-coagulant therapy. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening. Anti-platelet drugs are acceptable.
- •Treatment with another investigational drug or participation in another interventional clinical trial within 3 months of Screening;
- •Treatment with any human blood product, including IV immunoglobulin, during the 6 months prior to Screening or during the trial;
- •Pregnant or lactating;
- •Positive pregnancy test at Screening or Baseline (Day 1);
- •Cancer within 5 years of Screening, except for non-metastatic skin cancer or non-metastatic prostate cancer not expected to cause significant morbidity or mortality within one year of Baseline.
结局指标
主要结局
Number of patients experiencing drug limiting toxicity (DLT)
时间窗: 6 months
To determine the safety and tolerability of once monthly 4-unit transfusions of young (\<30 years of age) healthy male donor plasma for 6 months in patients with progressive supranuclear palsy (PSP). Number of patients experiencing drug limiting toxicity (DLT), defined as: 1) any Grade 3 or higher adverse event (AE) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) for which there is reasonable possibility that salsalate caused the event, 2) any Grade 2 AE in the CTCAE system organ class of nervous system disorders that is considered clinically significant and for which there is reasonable possibility that salsalate caused the event, or 3) any Grade 2 or higher treatment-related adverse events during administration that do not resolve promptly with supportive treatment
次要结局
- Changes in activities of daily living as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)(6 months)
- Changes in motor function as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)(6 months)
- Changes in cognition as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)(6 months)
- Changes in behavior as measured by Progressive Supranuclear Palsy Rating Scale (PSPRS)(6 months)