Clinical trial NCT03875560: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Dengue Fever
Lead sponsor: Implicit Bioscience
Sponsor class: INDUSTRY
First posted: 2019-03-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (safety, tolerability)
timeFrame: 32 days
measure: Area under the curve of IC14 serum concentration
timeFrame: 14 days
Secondary outcomes:
measure: Dengue viral load
timeFrame: 32 days
measure: Fever
timeFrame: 32 days
measure: Dengue symptom score
timeFrame: 32 days
measure: Disease severity
timeFrame: 32 days
measure: Mortality
timeFrame: 32 days
Other outcomes:
Locations:
Study officials:
affiliation: Implicit Bioscience
name: Jan Agosti, MD
role: STUDY_DIRECTOR
References: