TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients

NCT00867139 | Completed Phase 1 Results DMC

• 2 other identifiers: 2323.006895
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety and tolerability of triple combination antiviral drug (TCAD) for use in immunocompromised patients with Influenza A infection, and to gain data on the effectiveness of TCAD

Conditions

Influenza

Keywords

Influenza; Immunocompromised; Antiviral

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption

  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)

  30 days after the final dose of study drug

Secondary Outcomes (11)

• Number of Participants With Viral Load Decrease as a Function of Time

  baseline and 28 days

• Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1

  10 days

• Number of Participants With Viral Resistance as a Function of Drug Exposure

  28 days

• Duration of Symptoms

  from baseline up to 28 days

• Frequency of Confirmed Pneumonia

  58 days

Study Arms (3)

TCAD-Randomized Arm

EXPERIMENTAL

TCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate)

Drug: TCAD

Neuraminidase Monotherapy Arm

ACTIVE COMPARATOR

Zanamivir or Oseltamivir

Drug: Zanamivir or Oseltamivir

TCAD Open Label Arm

OTHER

TCAD for subjects who cannot tolerate or are ineligible to receive zanamivir

Other: Open label treatment with TCAD

Interventions

TCAD DRUG

TCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate)

Also known as: Symmetrel, Rebetol, Tamiflu

TCAD-Randomized Arm

Zanamivir or Oseltamivir DRUG

Zanamivir or Oseltamivir

Also known as: Relenza, Tamiflu

Neuraminidase Monotherapy Arm

Open label treatment with TCAD OTHER

TCAD(amantadine hydrocholoride, ribavirin and oseltamivir phosphate)

Also known as: Symmetrel, Rebetol, Tamiflu

TCAD Open Label Arm

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥7 years, male or female; AND
• Influenza infection (i.e. upper respiratory tract infection)
• Young age (1-6 years) with any influenza severity, proven or probable influenza A (H1N1)(H274Y); OR
• History of asthma; OR
• Older age (≥ 7 years), with no asthma; AND
• moderate to severe influenza; AND/OR
• \. Able to provide informed consent, or for whom consent may be provided by guardian 2. Immunocompromised, as defined by one of the following:
• Recent hematopoietic cell transplantation (HCT) (within 2 years, all conditioning regimens, allogeneic, autologous, syngeneic; after 2 years patients with chronic graft-versus-host disease (GVHD) requiring systemic treatment may be included) or solid organ transplantation
• Patients taking at least 2 immunosuppressants
• Patients undergoing combination chemotherapy within the past 3 month 3. One or more of the following:
• Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) taken orally.
• presence of at least one constitutional symptom (headache, myalgia, malaise, or fatigue) of any severity (mild, moderate, or severe),
• presence of at least one respiratory symptoms (e.g. cough, or sore throat) of any severity (mild, moderate, or severe),
• other flu-like symptoms, where the clinician orders a respiratory virus test including influenza A or B 4. Positive test for influenza A (if available) 5. Onset of illness no more than 5 days prior to diagnosis. 6. Females patients of child-bearing age who are capable of conception (i.e. previously have not undergone surgical sterilization) must meet the following criteria:
• Have been sexually abstinent or have used contraceptive agents (oral contraceptive or other hormonal contraceptives including vaginal rings or transdermal patches, intrauterine device (IUD), or barrier methods including condoms) during the 4 weeks prior to date of screening (3 months prior to enrollment for oral/hormonal contraceptives)

You may not qualify if:

• Nausea that prevents taking oral medications
• Creatinine clearance (estimated by serum creatinine) less than 30 ml/min
• Current clinical evidence of a recognized or suspected uncontrolled non-influenza infectious illness with onset prior to screening
• Known hypersensitivity to amantadine, ribavirin, oseltamivir or zanamivir
• Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding
• Psychiatric or cognitive illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance
• Uncontrolled seizure disorder or history of a seizure activity within 12 months prior to study participation
• Any significant finding in the patient's medical history or physical exam on Day 1 that, in the opinion of the investigator, would affect patient safety or compliance with the dosing schedule
• Documented Influenza B viral co-infection

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (2)

Seattle Children's

Seattle, Washington, 98105, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antivir Ther. 2013;18(3):377-86. doi: 10.3851/IMP2475. Epub 2012 Dec 21.

  PMID: 23264438 RESULT

MeSH Terms

Conditions

Influenza, Human

Interventions

thiazole-4-carboxamide adenine dinucleotide; Amantadine; Ribavirin; Oseltamivir; Zanamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Acetamides; Amides; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Guanidines; Amidines; Sialic Acids; Neuraminic Acids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Sugars; Carbohydrates

Limitations and Caveats

Study was terminated. Limitations of this study include: small sample size pilot study; inability to enroll the projected number of patients for full analysis before the study was terminated.

Results Point of Contact

• Title: Michael Boeckh MD
• Organization: FHCRC

mboeckh@fhcrc.org

206 667 6706

Study Officials

• Michael Boeckh, MD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Member, Vaccine and Infectious Disease Division

Study Record Dates

• First Submitted: March 20, 2009
• First Posted: March 23, 2009
• Study Start: March 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: January 1, 2010
• Last Updated: August 15, 2013
• Results First Posted: June 4, 2013

Record last verified: 2013-08

Locations

US (2)