ic14 in adult patients with dengue fever

Conditions: Dengue Fever

Summary: 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.

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.

Eligibility criteria:
inclusion criteria * 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. exclusion criteria * 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 \ 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.