withdrawn, no enrollment

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.

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 < 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.