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 - TCAD Therapy for treatment of influenza A in immunocompromised subjects
- Conditions
- Influenza A Virus
- Registration Number
- EUCTR2009-015850-39-NL
- Lead Sponsor
- Adamas Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 250
1. Male or female, between 1 and 65 years of age, inclusive (an individual investigative site may elect to enroll adults only, per local regulations or EC determination)
2. Able to provide informed consent, or for whom consent may be provided by guardian
3. Immunocompromised, as defined by one of the following at study entry:
• Recent solid organ transplantation or hematopoietic cell transplantation (HCT) (within 2 years, all conditioning regimens, allogeneic, autologous, or syngeneic)
• Chronic GVHD requiring systemic immunosuppression
• Taking at least 2 systemic immunosuppressants (regardless of dose)
• Received systemic chemotherapy within the past 3 months
• Taking high dose corticosteroids: an average daily dose of > 30 mg of prednisone (or equivalent dose for other corticosteroids) during 30 days prior to study entry
• HIV-positive with a CD4+ cell count <500/µL within 90 days prior to study entry
4. A clinical diagnosis of influenza (mild/moderate or severe) with the presence of one or more of the following:
•Presence of fever at time of screening of = 37.8°C (= 100.0°F) taken orally. However, this requirement is waived if the patient has a history of fever within the 24 hours prior to screening and has been administered any antipyretic(s) (including systemic steroids) in the 24 hours prior to screening
• Presence of at least one constitutional symptom (headache, myalgia, malaise, or fatigue) of any severity
• Presence of at least one respiratory symptom (e.g. cough, or sore throat) of any severity
• Other flu-like symptoms, where the clinician orders an influenza test
Severe influenza is defined for this study as:
• O2 saturation = 92% on room air; or
• Severe tachypnea (respiratory rate greater than or equal to 30 for ages greater than or equal to 12 years, rate greater than or equal to 40 for ages 6 to 12 years, rate greater than or equal to 45 for ages 3 to 6 years, rate greater than or equal to 50 for ages 1-3 years); or
• New infiltrate on chest X-ray (or any infiltrate if no prior chest X-ray or not known)
5. Positive rapid test for influenza A (standardized and sponsor-selected).
6. Subjects must be randomized no later than 5 days (120 hours) following estimated time of symptom onset. Note: Time of onset of illness is defined as either (1) the time when the temperature was first measured as elevated ( = 38.0°C (= 100.0°F)), OR (2) the time when the patient experienced the presence of at least one respiratory symptom or the presence of at least one constitutional symptom.
7. Females who are able to become pregnant (i.e. are not post-menopausal, have not undergone surgical sterilization, and are sexually active with men) must agree to use at least 2 effective forms of contraception from the date of informed consent through 24 weeks after the last dose of study drug. At least one of the methods of contraception should be a barrier method.
8. Males who have not undergone surgical sterilization and are sexually active with women must agree to use condoms plus have partner use at least one additional effective form of contraception from the date of informed consent through 24 weeks after the last dose of study drug.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Received more than one (1) dose of antiviral influenza medications since onset of influenza symptoms
2. Critically ill with presence of one or more of the following signs:
• need for admission to an intensive care unit (for other than respiratory isolation)
• acute respiratory failure requiring intubation/mechanical ventilation
• signs of shock including hypotension
3. Creatinine clearance less than 80 mL/min (estimated by the Cockcroft-Gault equation using serum creatinine) or, for pediatric subjects, a GFR less than 80 mL/min/1.73 m2 BSA (estimated by Schwartz or other age-appropriate formula)
4. History of gastrointestinal malabsorption
5. History of genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia
6. History of Chronic Active Hepatitis C
7. Hemoglobin less than 10 gm/dL
8. ANC <1000 cells/cubic millimeter
9. Known hypersensitivity to amantadine, ribavirin, or oseltamivir
10. Received amantadine, rimantadine, ribavirin, or oseltamivir for any indication within 30 days prior to study entry (may have received one (1) dose of antiviral influenza medication since onset of influenza symptoms)
11. Received live attenuated virus vaccine within 3 weeks prior to study entry
12. Received stavudine (d4T) or didanosine (ddI) within 30 days prior to study entry
13. Females who are pregnant, who are attempting to become pregnant, or who are breast-feeding
14. Males whose female partners are pregnant
15. Psychiatric or cognitive illness, including depression or suicidal ideation, or recreational drug/alcohol use that would affect patient safety and/or compliance
16. Uncontrolled seizure disorder or history of seizure activity within 12 months prior to study entry
17. Subjects with significant or unstable cardiac disease including angina, complex arrthymias, decompensated congestive heart failure and active ischemic disease
18. Documented non-influenza viral respiratory infection, including respiratory syncytial virus (RSV) or Influenza B
19. Use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study entry
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the antiviral efficacy of triple combination antiviral drug (TCAD) therapy (i.e., amantadine and ribavirin co-administered with oseltamivir) compared to oseltamivir monotherapy in immunocompromised subjects diagnosed with Influenza A;Secondary Objective: To investigate the clinical efficacy, viral resistance patterns, safety, and tolerability of triple combination antiviral drug (TCAD) therapy in comparison to oseltamivir monotherapy administered orally to immunocompromised subjects diagnosed with Influenza A;Primary end point(s): The primary endpoint is the time to clearing of viral shedding as determined by qRT-PCR using nasopharyngeal swabs.
- Secondary Outcome Measures
Name Time Method