IC14 in Adult Patients With Dengue Fever

Overview

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.

Full Title of Study: “A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of IC14 in Adult Patients With Dengue Fever”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Factorial Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: January 2020

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

  • Biological: IC14
    • recombinant chimeric anti-human CD14 monoclonal antibody
  • Drug: Placebo
    • Inactive

Arms, Groups and Cohorts

  • Experimental: 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).
  • Experimental: Part B/Cohort 1
    • IC14 4 mg/kg/day IV or placebo IV x 1 day.
  • Experimental: Part B/Cohort 2
    • IC14 8 mg/kg/day IV or placebo IV x 1 day.
  • Experimental: 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.
  • Experimental: 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.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of treatment-emergent adverse events (safety, tolerability)
    • Time Frame: 32 days
    • Number of patients with treatment-related adverse events as classified according to MedDRA
  • Area under the curve of IC14 serum concentration
    • Time Frame: 14 days
    • Area under the curve of IC14 serum concentration

Secondary Measures

  • Dengue viral load
    • Time Frame: 32 days
    • Impact of treatment on dengue viral load measured by quantitative viral load and plasma NS1 viral protein
  • Fever
    • Time Frame: 32 days
    • Impact of treatment on duration of fever
  • Dengue symptom score
    • Time Frame: 32 days
    • Impact of treatment on dengue symptom severity (0 normal] to 24 [worst])
  • Disease severity
    • Time Frame: 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
  • Mortality
    • Time Frame: 32 days
    • Impact of treatment on survival

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Implicit Bioscience
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jan Agosti, MD, Study Director, Implicit Bioscience

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