Dengue Fever
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALIC14
recombinant chimeric anti-human CD14 monoclonal antibody
DRUGPlacebo
Inactive
Sponsors
Implicit Bioscience
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (safety, tolerability) | 32 days | Number of patients with treatment-related adverse events as classified according to MedDRA |
| Area under the curve of IC14 serum concentration | 14 days | Area under the curve of IC14 serum concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dengue symptom score | 32 days | Impact of treatment on dengue symptom severity (0 normal\] to 24 \[worst\]) |
| Dengue viral load | 32 days | Impact of treatment on dengue viral load measured by quantitative viral load and plasma NS1 viral protein |
| Mortality | 32 days | Impact of treatment on survival |
| Disease severity | 32 days | Impact of treatment on duration of hospitalization; incidence and duration of intensive care unit admission; and incidence of progression to dengue with warning signs or severe dengue |
| Fever | 32 days | Impact of treatment on duration of fever |
Outcome results
None listed