Oral Triple Combination Antiviral Drug Therapy for Treatment of Influenza A in Immunocompromised Subjects

Study Overview
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Brief Summary
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This Phase 2, open label, randomized study will investigate the virologic benefit, clinical efficacy, safety, and tolerability of amantadine and ribavirin with oseltamivir (TCAD) versus oseltamivir monotherapy for the treatment of all strains of influenza A in immunocompromised adult and pediatric subjects.

Official Title
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A Randomized Open Label Study Comparing the Efficacy, Safety, and Tolerability of Oral Administration of Amantadine and Ribavirin With Oseltamivir Versus Oseltamivir to Influenza A Virus Infected Immunocompromised Subjects

Conditions
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Influenza

Intervention / Treatment
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* Drug: Oseltamivir Phosphate
* Drug: ADS-8902


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed influenza A by rapid antigen testing Immunocompromised as defined by recent solid organ or hematopoietic transplant, chronic graft vs. host disease, taking at least 2 immunosuppressants, undergoing chemotherapy, taking high dose chemotherapeutics, HIV positive Clinical diagnosis of influenza Onset of illness within 5 days Male and female subjects agree to contraception through 24 weeks after last dose Exclusion Criteria: Received more than 1 dose of antiviral agents Critically ill Creatinine clearance less than 80 mg/mL Females who are pregnant and males whose female partners are pregnant Received live attenuated virus vaccine within 3 weeks

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: ADS-8902<br>Amantadine and Ribavirin administered with Oseltamivir phosphate | Drug: ADS-8902<br>* Amantadine Hydrochloride, Ribavirin administered with Oseltamivir Phosphate, q8h<br>* Other names: Tamiflu®;|
| Active Comparator: Comparator<br>Oseltamivir Phosphate | Drug: Oseltamivir Phosphate<br>* Oseltamivir Phosphate, q8h<br>* Other names: Tamiflu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clearing of viral shedding |  | Baseline, Days 2, 4, 6, 8, 10, 15 and 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to alleviation of influenza clinical symptoms |  | Baseline, Days 2, 4, 6, 8, 10, 15, 20, 38 | 
| Proportion of subjects who enter the study with mild to moderate influenza and progress to severe influenza |  | Baseline, Days 2, 4, 6, 8, 10, 15, 20, 38 | 
| Proportion of subjects with a treatment-sensitive influenza A strain at baseline who develop a resistant strain during treatment |  | Baseline, Days 2, 4, 6, 8, 10, 15, 20 | 
| Safety and tolerability (adverse events (AEs), AEs resulting in treatment discontinuation, and Serious AEs) |  | Through day 210 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Immunocompromised, HIV, History of transplant