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

NCT00575185 | Completed Phase 1 Results DMC

• 1 other identifier: 0709M16341
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Infectious Mononucleosis

Keywords

Mono; Mononucleosis; Epstein-Barr virus

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Number of Participants Who Experienced Adverse Events During the Study Safety and Tolerability

  15 days

Study Arms (2)

Valomaciclovir

ACTIVE COMPARATOR

Valomaciclovir 2 grams orally twice daily for 21 days

Drug: Valomaciclovir

placebo

PLACEBO COMPARATOR

placebo 2 tablets twice daily for 21 days

Drug: placebo

Interventions

Valomaciclovir DRUG

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

Valomaciclovir

placebo DRUG

Placebo tablets orally twice daily for 21 days.

placebo

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Minnesota: lead
• Epiphany Biosciences: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (8)

• 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.

  PMID: 16206064 BACKGROUND

• 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.

  PMID: 17369082 BACKGROUND

• 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.

  PMID: 11458965 BACKGROUND

• 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.

  PMID: 17538884 BACKGROUND

• 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.

  PMID: 10680982 BACKGROUND

• 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.

  PMID: 11739180 BACKGROUND

• 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.

  PMID: 17378764 BACKGROUND

• 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.

  PMID: 16110323 BACKGROUND

MeSH Terms

Conditions

Infectious Mononucleosis; Epstein-Barr Virus Infections

Interventions

valomaciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Tumor Virus Infections

Results Point of Contact

• Title: Hank Balfour MD
• Organization: University of Minnesota

balfo001@umn.edu

(612) 626-5670

Study Officials

• Henry H Balfour, MD

  Professor of Laboratory Medicine & Pathology, and Pediatrics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 18, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: February 1, 2010
• Last Updated: March 22, 2017
• Results First Posted: March 17, 2015

Record last verified: 2017-02

Locations

US (1)