Activity of Valomaciclovir in Infectious Mononucleosis Due to Primary Epstein-Barr Virus Infection

Infectious Mononucleosis Clinical Trial

— Mono6  

Official title:

Randomized, Placebo-Controlled, Double-Blind Study to Assess Clinical and Antiviral Activity of Valomaciclovir (EPB 348) in Infectious Mononucleosis Due to Primary Epstein-Barr Virus Infection (Mono 6)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00575185
• Other study ID #: 0709M16341
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 14, 2007
• Last updated: March 13, 2015
• Start date: November 2007
• Est. completion date: February 2010

Study information

• Verified date: March 2015
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This will be a randomized, placebo-controlled, double-blind single-center proof of concept study to evaluate the anti-EBV activity of 4 grams of valomaciclovir (2 grams BID) for 21 days in subjects with infectious mononucleosis documented to be caused by primary EBV infection. Otherwise healthy subjects (≥15 years old) referred to us with a clinical diagnosis of primary infectious mononucleosis will be screened and those with laboratory-confirmed primary EBV infection will be enrolled.

Description:

Subjects will be seen 2 times a week for 3 weeks and then weekly for 3 weeks. Clinical findings, clinical lab tests, EBV viral loads, and EBV antibody titers will be obtained at each clinic visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: February 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Age 15 years or older

• Within 14 days of initial symptoms of present illness diagnosed by a health care provider as infectious mononucleosis and confirmed to be due to primary EBV by antibody profile. The criteria for antibody confirmation of primary EBV at the screening visit are: 1)Positive for anti-EBV VCA IgM antibody and negative for anti-EBV EBNA1 IgG antibody; 2)EBV antibody testing will be done in the Clinical Virology Research Laboratory using commercial ELISA kits (Diamedix Corporation, Miami, FL).

• Willingness to sign the Informed Consent Form (ICF)

• Willingness to contribute samples of blood and oral washings at regular intervals

• Males and females must use effective contraception during treatment and for at least 90 days following treatment

• Negative pregnancy test result at the Screening Visit for females of childbearing potential (including females who have had a bilateral tubal ligation). Female patients of childbearing potential must be willing to use an approved method of double-barrier contraception (hormonal plus barrier or barrier plus barrier, eg, diaphragm plus condom) from the time of first dose administration until 90 days after completion of dosing and male patients with female partners of childbearing potential must be willing to use a condom. Patients who are sterile or infertile (defined as those who are postmenopausal or have undergone a complete hysterectomy) are eligible.

• Estimated creatinine clearance (Cockcroft and Gault method) = 60 ml/min

• Absolute neutrophil count = 1000 cells/microliter

• Platelets = 100,000/microliter

• Hemoglobin = 9.5 g/dL

Exclusion Criteria:

• Previous history of infectious mononucleosis-like illness

• Immunosuppressed due to medical disease and/or immunosuppressive or immunomodulating medications (e.g., corticosteroids prior to enrollment, cytotoxic drugs, interferons)

• Another intercurrent viral infection (including HIV), based on history or referring physician medical evaluation

• More than 7 days elapsed since onset of illness (including screening time)

• The following concomitant medications are prohibited: probenecid, trimethoprim, myelosuppressive therapies, and medications known to be nephrotoxic

• Breast feeding during the study

• Corticosteroids are not permitted. If they are prescribed by the subject's primary physician for treatment of this acute disease after the subject has enrolled, the subject will be replaced.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Epstein-Barr Virus Infections
• Infection
• Infectious Mononucleosis
• Virus Diseases

Intervention

Drug:
• Valomaciclovir
4 grams orally of valomaciclovir (2 grams BID) for 21 days.
• placebo
Placebo tablets orally twice daily for 21 days.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	Epiphany Biosciences

Country where clinical trial is conducted

United States, 

References & Publications (8)

Balfour HH Jr, Hokanson KM, Schacherer RM, Fietzer CM, Schmeling DO, Holman CJ, Vezina HE, Brundage RC. A virologic pilot study of valacyclovir in infectious mononucleosis. J Clin Virol. 2007 May;39(1):16-21. Epub 2007 Mar 21. — View Citation

Balfour HH Jr, Holman CJ, Hokanson KM, Lelonek MM, Giesbrecht JE, White DR, Schmeling DO, Webb CH, Cavert W, Wang DH, Brundage RC. A prospective clinical study of Epstein-Barr virus and host interactions during acute infectious mononucleosis. J Infect Dis. 2005 Nov 1;192(9):1505-12. Epub 2005 Sep 26. — View Citation

Cameron B, Galbraith S, Zhang Y, Davenport T, Vollmer-Conna U, Wakefield D, Hickie I, Dunsmuir W, Whistler T, Vernon S, Reeves WC, Lloyd AR; Dubbo Infection Outcomes Study. Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis. J Infect Dis. 2007 Jul 1;196(1):56-66. Epub 2007 May 24. — View Citation

Hislop AD, Kuo M, Drake-Lee AB, Akbar AN, Bergler W, Hammerschmitt N, Khan N, Palendira U, Leese AM, Timms JM, Bell AI, Buckley CD, Rickinson AB. Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance. J Clin Invest. 2005 Sep;115(9):2546-55. Epub 2005 Aug 18. — View Citation

Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu Rev Immunol. 2007;25:587-617. Review. — View Citation

Rea TD, Russo JE, Katon W, Ashley RL, Buchwald DS. Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract. 2001 Jul-Aug;14(4):234-42. — View Citation

Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le TT, Morrison LE, Khanna R, Moss DJ, Suhrbier A, Misko IS. Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood. 2001 Dec 15;98(13):3739-44. — View Citation

Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31(6):543-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Improvement in Clinical Symptoms and Reductions in Viral Burden From Baseline	All subjects had confirmed cases of EB and will be assessed for Improvement of clinical symptoms (ie: tiredness, nausea etc)and reduction in viral burden from baseline	21 days	Yes
Secondary	Number of Participants Who Experienced Adverse Events During the Study Safety and Tolerability	Assessing adverse events in participants to see if this drug causes more or less side effects	15 days	Yes