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IC14 in Adult Patients With Dengue Fever

Primary Purpose

Dengue Fever

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
IC14
Placebo
Sponsored by
Implicit Bioscience
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dengue Fever

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part A/Single Dose

    Part B/Cohort 1

    Part B/Cohort 2

    Part B/Cohort 3

    Part B/Cohort 4

    Arm Description

    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).

    IC14 4 mg/kg/day IV or placebo IV x 1 day.

    IC14 8 mg/kg/day IV or placebo IV x 1 day.

    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.

    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.

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

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

    Full Information

    First Posted
    August 16, 2016
    Last Updated
    March 12, 2019
    Sponsor
    Implicit Bioscience
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03875560
    Brief Title
    IC14 in Adult Patients With Dengue Fever
    Official Title
    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
    Interventional

    2. Study Status

    Record Verification Date
    March 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    seeking funding
    Study Start Date
    May 2019 (Anticipated)
    Primary Completion Date
    January 2020 (Anticipated)
    Study Completion Date
    June 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Implicit Bioscience

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dengue Fever

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Factorial Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part A/Single Dose
    Arm Type
    Experimental
    Arm Description
    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).
    Arm Title
    Part B/Cohort 1
    Arm Type
    Experimental
    Arm Description
    IC14 4 mg/kg/day IV or placebo IV x 1 day.
    Arm Title
    Part B/Cohort 2
    Arm Type
    Experimental
    Arm Description
    IC14 8 mg/kg/day IV or placebo IV x 1 day.
    Arm Title
    Part B/Cohort 3
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Part B/Cohort 4
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    IC14
    Intervention Description
    recombinant chimeric anti-human CD14 monoclonal antibody
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Inactive
    Primary Outcome Measure Information:
    Title
    Incidence of treatment-emergent adverse events (safety, tolerability)
    Description
    Number of patients with treatment-related adverse events as classified according to MedDRA
    Time Frame
    32 days
    Title
    Area under the curve of IC14 serum concentration
    Description
    Area under the curve of IC14 serum concentration
    Time Frame
    14 days
    Secondary Outcome Measure Information:
    Title
    Dengue viral load
    Description
    Impact of treatment on dengue viral load measured by quantitative viral load and plasma NS1 viral protein
    Time Frame
    32 days
    Title
    Fever
    Description
    Impact of treatment on duration of fever
    Time Frame
    32 days
    Title
    Dengue symptom score
    Description
    Impact of treatment on dengue symptom severity (0 normal] to 24 [worst])
    Time Frame
    32 days
    Title
    Disease severity
    Description
    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
    Time Frame
    32 days
    Title
    Mortality
    Description
    Impact of treatment on survival
    Time Frame
    32 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    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 < 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jan Agosti, MD
    Organizational Affiliation
    Implicit Bioscience
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    IC14 in Adult Patients With Dengue Fever

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