Study of Alferon® LDO (Low Dose Oral) in Normal Volunteers

Study Overview
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Brief Summary
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The purpose of this trial is to conduct a randomized dose-ranging study to evaluate the safety and activity of orally administered low dose interferon alfa-n3 as an antiviral and immunomodulator in asymptomatic subjects with recent exposure to a person with severe acute respiratory syndrome (SARS) or possible SARS. The primary objective of this pilot study is to determine an Alferon LDO dose level that increases or upregulates genes known to be mediators of interferon response. Secondary endpoints include the development of SARS symptomatology, rate of hospitalization, and mortality rate. In the event that no subjects with recent exposure to a person with SARS or possible SARS are available, this study will be conducted with 10 normal volunteers.

Detailed Description
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This study will be an open-label, randomized, outpatient study in subjects potentially infected with the SARS-CoV (SARS-associated coronavirus) or normal volunteers using two dose levels of LDO interferon. Subjects will be randomized to receive Alferon® LDO (natural interferon alfa-n3) in a buffer solution once each day for 10 consecutive days at doses equal to 650 IU or 1300 IU/day. Pretherapy baseline evaluations will be performed prior to randomization. Subjects will be randomly assigned to each dose level, and both dosage levels will be started concurrently. Drug will be dispensed for a ten day treatment period, during which time any clinical symptoms and adverse events will be evaluated. Laboratory samples (2.5 ml blood) for microarray analysis evaluations will be made twice during baseline and 12-14 hours following doses 1, 5, and 10 on study days 2, 6, and 11, respectively. The conduct of this study will comply with International Conference on Harmonisation - Good Clinical Practice (ICH - GCP) and the 1996 or later version of the Declaration of Helsinki.

Official Title
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A Randomized, Dose-ranging Study of Alferon® LDO {Low Dose Oral Interferon Alfa-n3 (Human Leukocyte Derived)} in Normal Volunteers and/or Asymptomatic Subjects With Exposure to a Person Known to Have SARS or Possible SARS

Conditions
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Severe Acute Respiratory Syndrome

Intervention / Treatment
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* Drug: Alferon LDO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-80 years of age. Asymptomatic with close contact within the last 5 days with a person known to have possible SARS (SARS RUI-2 (SARS Report under investigation), RUI-3, RUI-4) or probable SARS or confirmed SARS using the Centers for Disease Control and Prevention (CDC) Supplement B: SARS Surveillance, Appendix B1: Revised Council of State and Territorial Epidemiologists (CSTE) SARS Surveillance Case Definition (Attachment II). Oral temperature < 100.4°F (<38°C) Subjects must be asymptomatic with regard to SARS related clinical symptoms including any signs of a respiratory illness. Serum creatinine ≤ 1.5 x ULN (upper limit of normal); serum bilirubin ≤ 1.5 x ULN. Total white blood cells (WBC) ≥ 3000/mm3, platelet count ≥ 100,000/mm3 and granulocytes ≥ 1500 mm3. Hemoglobin > 10.0 g/dl. ALT (alanine aminotransferase) and AST (aspartate aminotransferase) < 4 times upper normal limit. C-reactive protein serum level in normal range Serum albumin > 2.0 g/dl. Written informed consent. Females must either be of non-child bearing potential, or utilize an effective form of contraception and have a negative pregnancy test prior to randomization. Exclusion Criteria: Pregnant or nursing women, or women not using an effective form of contraception. Less than 18 years of age. Active intravenous (IV) drug users. Receipt of any immunosuppressive agent, chemotherapy, or systemic steroids within 45 days of study entry. Receipt of any immunomodulator such as BCG (bacille Calmette Guerin) vaccine, isoprinosine, or similar experimental agents within 45 days of study entry. Evidence of HIV or other viral infections including chronic hepatitis, or other active gastrointestinal, renal, respiratory, endocrine, hematologic, cardiovascular, neurological, or psychiatric disorder that would limit the subject's ability to complete the study period. Unlikely or unable to comply with the requirements of the protocol. Patients unwilling or unable to give informed consent. Patients on any other concurrent experimental medication. Patients using any form of interferon therapy during the 6 weeks prior to study entry. Hospitalized subjects, or those with an active viral infection other than possible SARS, within 2 weeks of study entry. Transfusion dependent subjects (subjects requiring > 1 unit of packed RBC [red blood cells] per month within the 3 months prior to study entry).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>650 IU | Drug: Alferon LDO<br> <br> |
| Active Comparator: 2<br>1300 IU | Drug: Alferon LDO<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression analysis | Increased expression of genes known to be mediators of interferon response. | Days 0, 2, 6, 11, 12, 15, 20 and 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS CoV Antibody | Development of clinical SARS-CoV symptomatology | Days 0, 15, 20 and 40 | 
| SARS-CoV infection | Hospitalization for SARS-CoV infection and Death |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS, Alferon LDO, Low Dose Oral Interferon ALFA-n3, Human Leukocyte Derived, Exposure to SARS, Possible SARS