IC14 in Adult Patients With Dengue Fever

NCT ID: NCT03875560

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2020-06-30

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.

Conditions

Dengue Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

IC14

Intervention Type: BIOLOGICAL

recombinant chimeric anti-human CD14 monoclonal antibody

Part B/Cohort 1

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

Group Type: EXPERIMENTAL

IC14

Intervention Type: BIOLOGICAL

recombinant chimeric anti-human CD14 monoclonal antibody

Placebo

Intervention Type: DRUG

Inactive

Part B/Cohort 2

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

Group Type: EXPERIMENTAL

IC14

Intervention Type: BIOLOGICAL

recombinant chimeric anti-human CD14 monoclonal antibody

Placebo

Intervention Type: DRUG

Inactive

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.

Group Type: EXPERIMENTAL

IC14

Intervention Type: BIOLOGICAL

recombinant chimeric anti-human CD14 monoclonal antibody

Placebo

Intervention Type: DRUG

Inactive

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.

Group Type: EXPERIMENTAL

IC14

Intervention Type: BIOLOGICAL

recombinant chimeric anti-human CD14 monoclonal antibody

Placebo

Intervention Type: DRUG

Inactive

Interventions

IC14

recombinant chimeric anti-human CD14 monoclonal antibody

Intervention Type: BIOLOGICAL

Placebo

Inactive

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Implicit Bioscience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Agosti, MD

Role: STUDY_DIRECTOR

Implicit Bioscience

Other Identifiers

EDF-01

Identifier Type: -

Identifier Source: org_study_id