IC14 in Adult Patients With Dengue Fever
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
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). |
Biological: IC14
recombinant chimeric anti-human CD14 monoclonal antibody
|
Experimental: Part B/Cohort 1 IC14 4 mg/kg/day IV or placebo IV x 1 day. |
Biological: IC14
recombinant chimeric anti-human CD14 monoclonal antibody
Drug: Placebo
Inactive
|
Experimental: Part B/Cohort 2 IC14 8 mg/kg/day IV or placebo IV x 1 day. |
Biological: IC14
recombinant chimeric anti-human CD14 monoclonal antibody
Drug: Placebo
Inactive
|
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. |
Biological: IC14
recombinant chimeric anti-human CD14 monoclonal antibody
Drug: Placebo
Inactive
|
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. |
Biological: IC14
recombinant chimeric anti-human CD14 monoclonal antibody
Drug: Placebo
Inactive
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Dengue viral load [32 days]
Impact of treatment on dengue viral load measured by quantitative viral load and plasma NS1 viral protein
- Fever [32 days]
Impact of treatment on duration of fever
- Dengue symptom score [32 days]
Impact of treatment on dengue symptom severity (0 normal] to 24 [worst])
- 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
- Mortality [32 days]
Impact of treatment on survival
Eligibility Criteria
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Implicit Bioscience
Investigators
- Study Director: Jan Agosti, MD, Implicit Bioscience
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EDF-01