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

NCT ID: NCT00575185

Last Updated: 2017-03-22

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2010-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infectious Mononucleosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Valomaciclovir

Valomaciclovir 2 grams orally twice daily for 21 days

Group Type ACTIVE_COMPARATOR

Valomaciclovir

Intervention Type DRUG

4 grams orally of valomaciclovir (2 grams BID) for 21 days.

placebo

placebo 2 tablets twice daily for 21 days

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Placebo tablets orally twice daily for 21 days.

Interventions

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Valomaciclovir

4 grams orally of valomaciclovir (2 grams BID) for 21 days.

Intervention Type DRUG

placebo

Placebo tablets orally twice daily for 21 days.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Epiphany Biosciences

INDUSTRY

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Henry H Balfour, MD

Role: PRINCIPAL_INVESTIGATOR

Professor of Laboratory Medicine & Pathology, and Pediatrics

Locations

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University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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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. doi: 10.1086/491740. Epub 2005 Sep 26.

Reference Type BACKGROUND
PMID: 16206064 (View on PubMed)

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. doi: 10.1016/j.jcv.2007.02.002. Epub 2007 Mar 21.

Reference Type BACKGROUND
PMID: 17369082 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11458965 (View on PubMed)

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. doi: 10.1086/518614. Epub 2007 May 24.

Reference Type BACKGROUND
PMID: 17538884 (View on PubMed)

Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31(6):543-7. doi: 10.1080/00365549950164409.

Reference Type BACKGROUND
PMID: 10680982 (View on PubMed)

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. doi: 10.1182/blood.v98.13.3739.

Reference Type BACKGROUND
PMID: 11739180 (View on PubMed)

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. doi: 10.1146/annurev.immunol.25.022106.141553.

Reference Type BACKGROUND
PMID: 17378764 (View on PubMed)

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. doi: 10.1172/JCI24810. Epub 2005 Aug 18.

Reference Type BACKGROUND
PMID: 16110323 (View on PubMed)

Other Identifiers

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0709M16341

Identifier Type: -

Identifier Source: org_study_id

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