NCT04365101终止1 期
A Phase I/II Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) for the Treatment of Adults With COVID-19
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 13
- 主要终点
- Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI)
研究概览
简要总结
This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.
详细描述
This Phase 1/2 study evaluated the safety and potential efficacy of CYNK-001, an allogeneic natural killer (NK) cell therapy derived from human placental CD34+ cells, in adult patients with moderate COVID-19. Participants received intravenous infusions of CYNK-001 on Days 1, 4, and 7. CYNK-001 IV infusions administered at an initial desensitizing dose of 150 × 106 cells on Day 1 followed by a dose of 600 × 106 cells on Days 4 and 7 plus best supportive care. The study was designed to include a Phase 1 dose-escalation portion followed by a randomized Phase 2 portion; however, due to early termination, only Phase 1 participants were enrolled and treated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Patient Inclusion Criteria:
- •Patient has confirmed positivity for SARS-CoV-2 as measured by rRT-PCR or other approved test to detect SAR-CoV-2 per institutional practice.
- •Patient is experiencing any symptom/clinical sign of COVID-19 illness or has a positive disease-related chest x-ray/CT scan at screening.
- •Patient is ≥ 18 years of age at the time of signing the Study informed consent form (ICF).
- •Patient understands and voluntarily signs the Study ICF prior to any study-related assessments/procedures are conducted.
- •Patient is willing and able to adhere to the study schedule and other protocol requirements.
- •SpO2 ≥ 88% on room air; oxygen is permitted as delivered by nasal cannula and/or face mask at any flow rate to achieve this SpO
- •Patients must have an SpO2 ≥ 92% if on supplementary oxygen.
- •Ability to be off immunosuppressive drugs for 3 days prior to infusion, unless clinically indicated. Steroids are permitted if clinically indicated and at the discretion of the treating physician. If clinically indicated, careful consideration should be taken regarding the timing and tapering of high-dose steroids.
- •Female of childbearing potential (FCBP)* must not be pregnant and agree to not becoming pregnant for at least 28 days following the last infusion of CYNK-
- •FCBP must agree to use an adequate method of contraception during the treatment period.
- •FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- •Male Patients must agree to use a condom during sexual contact for at least 28 days following the last infusion of CYNK-001, even if he has undergone a successful vasectomy.
排除标准
- •Patient requires supplemental oxygen delivered by mechanical ventilation, either invasive or bilevel positive airway pressure.
- •Patient admitted to Intensive Care Unit / Pulmonary Acute Care Unit designated area with severe pulmonary pneumonia, ARDS or Sepsis.
- •Patient is pregnant or breastfeeding.
- •Patient has a history of chronic asthma requiring ongoing medical therapy or other chronic pulmonary disease that, at the discretion of the treating physician, would contraindicate participation in this study.
- •Patient has any other organ dysfunction [Common Terminology Criteria for AEs (CTCAE) Version 5.0 Grade 3] that will interfere with the administration of the therapy according to this protocol.
- •Patient has inadequate organ function as defined below at time of Treatment Eligibility Period:
- •Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 5 x the upper limit of normal (ULN). (It is anticipated that the infection may impact liver.)
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m^2 as calculated using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history of an abnormal eGFR <
- •A decline of > 15 mL/min/1.73 m^2 below normal in the past year prior to infection. (It is anticipated that the infection may impact renal function.)
- •Patient has a bilirubin level > 2 mg/dL (unless Patient has known Gilbert's Syndrome).
- •Patient has a known sensitivity or allergy to treatment additives or diluent substances of dimethyl sulfoxide (DMSO), PlasmaLyte A or human serum albumin (HSA). Please refer to investigational brochure (IB).
- •Patient has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
- •Patient is immunocompromised, has known human immunodeficiency virus (HIV) positivity, or has actively been treated with immunosuppressive products prior to being infected with SARS-CoV-
- •Patient has known active malignancy, unless the Patient has been free of disease for > 3 years from the date of signing the ICF. Exceptions include the following noninvasive malignancies:
- •Basal cell carcinoma of the skin
- •Squamous cell carcinoma of the skin
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
- •Detection of other respiratory viruses from mucosal surfaces that would interfere with the study treatment plan; detection of another respiratory virus is not in itself an exclusion criteria unless the investigator believes it would interfere with administration of CYNK-
- •Patient must not have a history of unconsciousness or hemoptysis within 2 weeks of signing informed consent form.
- •Patients must not have a history of unconsciousness or hemoptysis within 2 weeks of signing ICF.
- •Patients must not have end stage liver disease and/or cirrhosis.
- •Patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
- •Patient has any condition including the presence of laboratory abnormalities which places the patient at unacceptable risk if he or she were to participate in the study.
- •Patient has any condition that confounds the ability to interpret data from the study.
研究组 & 干预措施
Phase I
Experimental
CYNK-001 infusions on Days 1, 4, and 7. CYNK-001 IV infusions administered at an initial desensitizing dose of 150 × 106 cells on Day 1 followed by a dose of 600 × 106 cells on Days 4 and 7 plus best supportive care.
干预措施: CYNK-001 (Biological)
Phase II
Active Comparator
Randomized, open label; CYNK-001 infusions on Days 1, 4, and 7 compared to Control Group: Best Supportive Care.
干预措施: CYNK-001 (Biological)
结局指标
主要结局
Phase 2: Time to Clinical Improvement by Ordinal Scale for Clinical Improvement (OSCI)
时间窗: Study Day 28
Time to clinical improvement measured by OSCI
Phase 1 Futility Check for go/no decision to move to Phase 2: Rate of clinical improvement
时间窗: Study Day 15
Proportion of patients who improved clinical symptoms as measured by the Ordinal Scale for Clinical Improvement (OSCI)
Phase 1: Frequency and Severity of Adverse Events (AE)
时间窗: Up to 6 months
Number and severity of adverse events
次要结局
- Overall Clinical Benefit by time to medical discharge(up to 6 months)
- Time to Pulmonary Clearance(Up to 28 days)
- Proportion of patients requiring ventilation(Up to 28 days)
- Duration of hospitalization(Study Day 28)
- All-cause mortality rate(Study Day 28 and Month 6)
- Time to clinical improvement by NEWS2 Score(Study Day 28)
- Rate of Clearance of SARS-CoV-2(Study Day 28)
- Overall Clinical Benefit by measuring mortality rate(up to 6 months)
- Radiologic Evaluation Score(Study Day 28 and Month 6)
- Time to Clearance of SARS-CoV-2(Study Day 28)
- Phase 2: Frequency and Severity of Adverse Events (AE)(up to 6 months)
- Rate of Pulmonary Clearance(Up to 28 days)
- Overall Clinical Benefit by hospital utilization(up to 6 months)
- Impact of CYNK-001 on sequential organ failure assessment (SOFA) score(Up to 28 days)
- Supplemental oxygen-free days(Up to 28 days)
- Rate of clinical improvement by NEWS2 Score(Study Day 28)
研究者
研究点 (13)
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