Trial Outcomes & Findings for TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients (NCT NCT00867139)

NCT ID: NCT00867139

Last Updated: 2013-08-15

Results Overview

Abnormal lab data or newly appeared symptoms \& signs were considered as AEs. Examined lab data: Blood cell count (WBC, differential count, Red Blood Cell (RBC), Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), platelets), Chemistry (Cl, bicarbonate (HCO3), K, Na), Renal function test (BUN, Creatinine, Creatinine clearance), Liver function test (AST, Alanine aminotransferase(ALT), T.Bil, gamma-glutamyltransferase)

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 7 participants
• Primary outcome timeframe: 30 days after the final dose of study drug
• Results posted on: 2013-08-15

Participant Flow

Patients were recruited from subjects who had a hematopoietic cell transplantation (HCT) within 2 years or combination chemotherapy within 3 months, those with chronic graft-versus-host disease (GVHD) requiring systemic treatment after 2 years post HCT, or with GVHD taking at least 2 immunosuppressive drugs between February - September, 2009

Participant milestones

Measure	TCAD This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic.	Neuraminidase Inhibitor Monotherapy This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic.	Open-labeled TCAD This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic.
Overall Study STARTED	2	1	4
Overall Study COMPLETED	2	1	3
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients

Baseline characteristics by cohort

Measure	TCAD n=2 Participants This substudy was a randomized study comparing TCAD therapy and OSL monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic.	Neuraminidase Inhibitor Monotheraphy n=1 Participants Neuraminidase inhibitors include zanamivir and oseltamivir phosphate in this study.	Open-Labeled TCAD n=4 Participants Subjects with moderate respiratory symptoms and/or influenza-related lower respiratory tract disease, subjects who could not tolerate zanamivir, and children aged 1-6 years received open-label TCAD.	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Age Continuous	59.5 years STANDARD_DEVIATION 17.7 • n=5 Participants	17 years STANDARD_DEVIATION 0 • n=7 Participants	29.5 years STANDARD_DEVIATION 26.0 • n=5 Participants	36.3 years STANDARD_DEVIATION 25.7 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	2 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	7 participants n=4 Participants

PRIMARY outcome

Timeframe: 30 days after the final dose of study drug

Abnormal lab data or newly appeared symptoms & signs were considered as AEs.

Examined lab data:

Blood cell count (WBC, differential count, Red Blood Cell (RBC), Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), platelets), Chemistry (Cl, bicarbonate (HCO3), K, Na), Renal function test (BUN, Creatinine, Creatinine clearance), Liver function test (AST, Alanine aminotransferase(ALT), T.Bil, gamma-glutamyltransferase)

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=4 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption	1 number of participants with AEs	1 number of participants with AEs	1 number of participants with AEs

SECONDARY outcome

Timeframe: baseline and 28 days

Population: Three patients could not get viral load at baseline.

Viral loads were measured by quantitative Polymerase Chain Reaction (PCR) on day 1, 3, 5, 7, 9, 15, 20 and 28, if applicable.

Outcome measures

Measure	TCAD amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Participants With Viral Load Decrease as a Function of Time	—	0 number of participants	2 number of participants

SECONDARY outcome

Timeframe: 10 days

Population: Participants assessed for viral shedding were those with available baseline viral load data.

Outcome measures

Measure	TCAD amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1 Day 5 +/-1	—	0 participants	0 participants
Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1 Day 10 +/- 1	—	0 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Population: One open-labeled patient withdrew on day 5.

Viral resistance was assessed within 28 days after drug administration by detecting resistance-conferring mutation genes and compared to the value at baseline.

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Participants With Viral Resistance as a Function of Drug Exposure	0 Number of participants	1 Number of participants	0 Number of participants

SECONDARY outcome

Timeframe: from baseline up to 28 days

Population: one open labeled patient withdrew on day 5.

Calculated as the number of days (mean) any persistent symptom lasted per patient as listed below.

overall health, short of breath, chills, cough, diarrhea, ear pain, fatigue, fever, headache, hoarseness, muscle ache, phlegm, runny nose, sinus congestion, sneezing, sore throat, watery eyes, wheezing

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Duration of Symptoms	4.5 days Standard Deviation 6.4	1 days	4.7 days Standard Deviation 3.8

SECONDARY outcome

Timeframe: 58 days

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=4 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Frequency of Confirmed Pneumonia	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: from baseline up to 58 days

Population: One open-labeled patient withdrew the study on day 5

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Duration of Hospitalization	6 days Standard Deviation 8.5	6 days	1 days Standard Deviation 1.7

SECONDARY outcome

Timeframe: 58 days

Population: One open-labeled TCAD patient withdrew on day 5.

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Days on Supplemental Oxygen	2 days Standard Deviation 1.4	0 days	0 days Standard Deviation 0

SECONDARY outcome

Timeframe: baseline and up to 58 days

The number of participants with ICU admissions was evaluated.

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=4 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Participants With ICU Admissions	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: 58 days

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=4 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Participants With Intubations	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: 58 days

Outcome measures

Measure	TCAD n=2 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=4 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Number of Deaths	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 5 days

Only 5 patients had partial pharmacokinetic (PK) data available. Plasma concentration of oseltamivir was measured at several time points in one patient receiving neuraminidase inhibitor monotherapy. Plasma concentration of oseltamivir, amantadine, and ribavirin were measured at several time points in four patients receiving TCAD therapy. Area under the time-concentration curve up to the last measured time point (AUC0-last) was calculated from the plasma concentration-time profiles by non-compartmental analysis.

Outcome measures

Measure	TCAD n=1 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days	Neuraminidase Inihibitor Monotherapy n=1 Participants oseltamivir (50 mg); three times a day for 10 days	Open-labeled TCAD n=3 Participants amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Pharmacokinetics (AUC0-last) of TCAD	304 ng*hr/mL	1497 ng*hr/mL	2487 ng*hr/mL Standard Deviation 2770

Adverse Events

TCAD

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Neuraminidase Inihibitor Monotherapy

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Open-labeled TCAD

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	TCAD n=2 participants at risk Eligible immunocompromised subjects( age\>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy.	Neuraminidase Inihibitor Monotherapy n=1 participants at risk Eligible immunocompromised subjects( age\>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy.	Open-labeled TCAD n=4 participants at risk Subjects with moderate respiratory symptoms and/or influenza-related lower respiratory tract disease, subjects who could not tolerate zanamivir, and children aged 1-6 years received.
Gastrointestinal disorders Acute GVHD	50.0% 1/2 • Number of events 1	100.0% 1/1 • Number of events 1	0.00% 0/4
Respiratory, thoracic and mediastinal disorders ARDS	0.00% 0/2	0.00% 0/1	25.0% 1/4 • Number of events 1

Other adverse events

Measure	TCAD n=2 participants at risk Eligible immunocompromised subjects( age\>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy.	Neuraminidase Inihibitor Monotherapy n=1 participants at risk Eligible immunocompromised subjects( age\>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy.	Open-labeled TCAD n=4 participants at risk Subjects with moderate respiratory symptoms and/or influenza-related lower respiratory tract disease, subjects who could not tolerate zanamivir, and children aged 1-6 years received.
Skin and subcutaneous tissue disorders acute GVHD	50.0% 1/2 • Number of events 1	0.00% 0/1	0.00% 0/4
Gastrointestinal disorders acute GVHD	50.0% 1/2 • Number of events 1	0.00% 0/1	0.00% 0/4
Cardiac disorders tachycardia	50.0% 1/2 • Number of events 1	0.00% 0/1	0.00% 0/4
Hepatobiliary disorders increased ALP and GGT	50.0% 1/2 • Number of events 1	0.00% 0/1	0.00% 0/4

Additional Information

Michael Boeckh MD

FHCRC

Phone: 206 667 6706

Email: mboeckh@fhcrc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place