A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of IC14 in Adult Patients With Dengue Fever
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Area under the curve of IC14 serum concentration
研究概览
简要总结
Randomized, double-blind, placebo-controlled, safety, PK/PD and preliminary efficacy study of intravenous IC14 in adult patients in a dengue-endemic region presenting with fever > 38°C for < 48 hours with a positive NS1 strip assay or reverse-transcriptase polymerase chain reaction assay for dengue virus.
详细描述
The study will be conducted in two parts and will include an open label phase of a single dose of IC14 (Part A) and a randomized phase of multiple doses of IC14 and placebo (Part B). Up to 52 patients will be enrolled in both parts of the study.
Part A will consist of 12 patients given one of three doses of IC14 as a single dose open-label . Each patient must complete 14 days before the enrollment of subsequent patients. Part A subjects will be hospitalized for 4 days. During and at the end of 4-day admission to the clinical research unit, and on Study Days 5, 6, 7, 14, 21 and 32, Part A patients will have their health status assessed. The last subject in Part A must complete 32 days of participation before Part B of the trial is opened.
Part B consists of 40 patients randomized equally to one of 4 dosing regimens which will include a single dose or multiple doses of IC14 or placebo given at different dosing frequencies. In Part B, Cohort 1 and 2 subjects (single dose) will be inpatient for 4 days and Cohort 3 and 4 subjects (four daily doses) will be inpatient for 5 days. During and at the end of the admission to the clinical research unit, and on Study Days 5, 6, 7, 14, 21 and 32, Part B patients will have their health status assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fever > 38°C for < 48 hours and clinical presentation consistent with dengue fever.
- •Positive NS1 strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR) assay for dengue virus.
- •Informed consent form signed and dated by the patient.
- •Subject able to give informed consent and able to comply with all study visits and all study procedures.
- •Females of childbearing potential should be using and committed to continue using acceptable birth control methods.
- •Sexual abstinence (inactivity) for 1 month prior to screening through study completion; or
- •Intrauterine device (IUD) in place for at least 3 months prior to study through study completion; or
- •Stable hormonal contraception for at least 3 months prior to study through study completion; or
- •Surgical sterilization (vasectomy) of male partner at least 6 months prior to study.
- •To be considered of non-childbearing potential, females should be surgically sterilized (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 2 months prior to study) or be post-menopausal and at least 3 years since last menses.
排除标准
- •One or more of the following dengue warning signs and symptoms:
- •Intense and continuous abdominal pain (referred pain or on palpation);
- •Persistent vomiting;
- •Fluid accumulation (ascites, pleural effusion, or pericardial effusion);
- •Postural hypotension and/or collapse;
- •Painful hepatomegaly > two centimeters below the right costal margin;
- •Mucosal bleeding;
- •Major bleeding (hematemesis and/or melena);
- •Lethargy and/or irritability;
- •Diminished urine output;
- •Hypothermia;
- •Progressive increase in hematocrit or 20% above baseline or normal for age;
- •Abrupt drop in platelets;
- •Respiratory discomfort.
- •One or more of the following signs and symptoms of severe dengue, such as:
- •Severe plasma extravasation, leading to shock evidenced by one or more of the following:
- •Tachycardia;
- •Cold distal extremities;
- •Weak, thready pulse;
- •Slow capillary refill (> 2 seconds);
- •Pulse pressure < 20 mmHg;
- •Tachypnea; or
- •Oliguria (<1.5 mL/kg/hr).
- •Systolic blood pressure < 90 mmHg or decrease >40 mmHg;
- •Cyanosis;
- •Fluid accumulation with respiratory discomfort;
- •Severe bleeding; or
- •Severe organ impairment, evidenced by one or more of the following:
- •Liver impairment (AST >1000 U/L, international normalized ratio >1.5);
- •Renal impairment (serum creatinine ≥1.5 mg/dL); or
- •Myocarditis, pericarditis, or clinical heart failure (by chest x-ray, echocardiography, electrocardiogram, or cardiac enzymes if available).
- •Female who is pregnant, lactating or of childbearing potential.
- •Self-reported or suspected congenital or acquired immunodeficiency (including HIV infection); or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the previous 3 months).
- •Prior vaccination against dengue fever.
- •Significant chronic illness that, in the opinion of the Investigator, would interfere with study validity, conduct or completion.
研究组 & 干预措施
Part B/Cohort 2
IC14 8 mg/kg/day IV or placebo IV x 1 day.
干预措施: Placebo (Drug)
Part B/Cohort 1
IC14 4 mg/kg/day IV or placebo IV x 1 day.
干预措施: Placebo (Drug)
Part B/Cohort 2
IC14 8 mg/kg/day IV or placebo IV x 1 day.
干预措施: IC14 (Biological)
Part B/Cohort 3
IC14 2 mg/kg/day IV x 1 day followed by IC14 1 mg/kg/day IV x 3 days or placebo IV daily for 4 days.
干预措施: Placebo (Drug)
Part B/Cohort 4
IC14 4 mg/kg/day IV x 1 day followed by IC14 2 mg/kg/day IV x 3 days or placebo IV daily for 4 days.
干预措施: Placebo (Drug)
Part B/Cohort 4
IC14 4 mg/kg/day IV x 1 day followed by IC14 2 mg/kg/day IV x 3 days or placebo IV daily for 4 days.
干预措施: IC14 (Biological)
Part B/Cohort 3
IC14 2 mg/kg/day IV x 1 day followed by IC14 1 mg/kg/day IV x 3 days or placebo IV daily for 4 days.
干预措施: IC14 (Biological)
Part B/Cohort 1
IC14 4 mg/kg/day IV or placebo IV x 1 day.
干预措施: IC14 (Biological)
Part A/Single Dose
IC14 0.5, 1.0 or 2.0 mg/kg IV as a single dose (subjects are assigned and not randomized to this arm. When Part A is complete, Enrollment to Part B will commence).
干预措施: IC14 (Biological)
结局指标
主要结局
Area under the curve of IC14 serum concentration
时间窗: 14 days
Area under the curve of IC14 serum concentration
Incidence of treatment-emergent adverse events (safety, tolerability)
时间窗: 32 days
Number of patients with treatment-related adverse events as classified according to MedDRA
次要结局
- Dengue viral load(32 days)
- Dengue symptom score(32 days)
- Disease severity(32 days)
- Mortality(32 days)
- Fever(32 days)