LB-1. Six months versus six weeks of oral valganciclovir for infants with symptomatic congenital cytomegalovirus (CMV) disease with and without central nervous system (CNS) involvement: Results of a Phase III, randomized, double-blind, placebo-controlled, multinational study
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 5, 2013: 10:30 AM
Room: The Moscone Center: 102 (Gateway Ballroom)
Background: 6 weeks of intravenous (IV) ganciclovir (GCV) improves long-term hearing outcomes in infants with symptomatic congenital CMV disease involving the CNS.

Method: The NIAID CASG conducted a Phase III trial of 6 weeks vs. 6 months of oral valganciclovir (VGCV).  Subjects ≤ 30 days with symptomatic congenital CMV disease with or without CNS involvement were enrolled.  Hearing was assessed at baseline (BL), 6, 12, and 24 months, and neurodevelopment was assessed at 12 and 24 months by Bayley-III.  Safety labs and viral load were followed.

Result: From 2008 to 2011, 109 subjects (218 total ears) were enrolled. 

 

Change in hearing between baseline and follow-up (F/U) (total ears)

Follow-up

6 months

12 months

24 months

Duration of VGCV therapy

6 wks (n=84)

6 mos (n=82)

6 wks (n=77)

6 mos (n=79)

6 wks (n=58)

6 mos (n=70)

Improved hearing

7 (8.3%)

6 (7.3%)

4 (5.1%)

6 (7.6%)

2 (3.5%)

6 (8.6%)

Normal hearing at BL and F/U

39 (46.4%)

46 (56.1%)

40 (50.6%)

52 (65.8%)

35 (60.3%)

48 (68.6%)

Same degree of hearing loss at BL and F/U

29 (34.5%)

19 (23.2%)

23 (29.9%)

15 (19.0%)

16 (27.6%)

8 (11.4%)

Worsened hearing

9 (10.7%)

11 (13.4%)

10 (13.0%)

6 (7.6%)

5 (8.6%)

8 (11.3%)

Logistic regression analysis

Hearing Improved or Normal at BL and F/U, vs Others

Hearing Improved or Normal at BL and  F/U, vs Others

Hearing Improved or Normal at BL and F/U, vs Others

P

OR (95% CI)

P

OR (95% CI)

P

0.1915

3.34 (1.31, 8.53)

0.0117

2.66 (1.02, 6.91)

0.0444

Language (p=0.0046) and receptive communication (p=0.0031) scores were superior at 24 months in the 6-month treatment group compared with the 6-week group.  During the first 6 weeks of therapy, 19.3% of subjects experienced Grade 3-4 neutropenia.  From week 6 through month 6, 21.3% of subjects on VGCV and 26.5% of subjects on placebo had Grade 3-4 neutropenia (p=0.6353).  One subject had the VGCV dose temporarily held due to neutropenia.

Conclusion: 6 months of oral VGCV treatment of infants with symptomatic congenital CMV disease improves audiologic and neurodevelopmental outcomes to at least 2 years of age.  Less neutropenia is seen during the first 6 weeks of treatment with VGCV (19.3%) than was seen in an earlier CASG study of IV GCV (63%), and there is no excess neutropenia with continuation of VGCV treatment from 6 weeks to 6 months compared with placebo.

David W. Kimberlin, MD, FIDSA1, Penelope Jester, MSN BSN2, Pablo J. Sanchez, MD, FIDSA3, Amina Ahmed, MD4, Ravit Arav-Boger5, Sunil Sood, MD6, Charles Woods, MD, MS, FIDSA, FSHEA7, Negar Ashouri, MD8, Janet A. Englund, MD, FIDSA9, Benjamin Estrada, MD10, Richard Jacobs, MD11, Jose R. Romero, MD12, Suzanne Whitworth, MD13, Mark J Abzug, MD14, Mary T. Caserta, MD15, Sandra Fowler, MD16, Jorge Lujan-Zilbermann, MD17, Gregory Storch, MD, FIDSA18, Robert W. Tolan Jr., MD19, Roberta Debiasi, MD20, Jin-Young Han21, April Palmer, MD22, Leonard Weiner, MD23, Joseph Bocchini Jr., MD, FAAP24, Penelope Dennehy, MD25, Adam Finn, MD, PhD26, Paul Griffiths, MD27, Kathleen Gutierrez, MD28, Natasha Halasa, MD MPH29, James Homans, MD30, Andi L. Shane, MD, MPH, MSc31, Mike Sharland, MD32, Kari Simonsen, MD33, John A. Vanchiere, M.D., Ph.D.34, Inmaculada Aban, PhD2, Edward Acosta, PharmD35, Richard Whitley, MD, FIDSA36, Marian Michaels, MD, MPH37 and the NIAID Collaborative Antiviral Study Group (CASG), (1)University of Alabama At Birmingham, Birmingham, AL, (2)University of Alabama at Birmingham, Birmingham, AL, (3)University of Texas Southwestern Medical Center, Dallas, TX, (4)Carolinas Medical Center, Charlotte, NC, (5)Johns Hopkins, Baltimore, MD, (6)Steven & Alexandra Cohen Children's Medical Center, Manhasset, NY, (7)Pediatrics, University of Louisville School of Medicine, Louisville, KY, (8)Infectious Diseases, CHOC Children's Hospital, Orange, CA, (9)Seattle Children's Hospital, Seattle, WA, (10)University of South Alabama, Mobile, AL, (11)University of Arkansas, Little Rock, AR, (12)University of Arkansas for Medical Sciences, Little Rock, AR, (13)Cook Children's Medical Center, Fort Worth, TX, (14)University of Colorado School of Medicine, Aurora, CO, (15)University of Rochester School of Medicine, Rochester, NY, (16)Medical University of South Carolina, Charleston, SC, (17)Pediatrics, University of South Florida College of Medicine, Tampa, FL, (18)St. Louis Children's Hospital, St. Louis, MO, (19)Pediatrics, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, NJ, (20)Children's National Medical Center/Children's Research Institute, Washington, DC, (21)University of Minnesota, Minneapolis, MN, (22)Pediatrics, University of Mississippi Medical Center, Jackson, MS, (23)Pediatrics, SUNY Upstate Medical University, Syracuse, NY, (24)Pediatrics, Louisiana State University Health - Shreveport, Shreveport, LA, (25)Pediatric Infectious Disease, Hasbro Childrens Hospital, Brown University, Providence, RI, (26)School of Clinical Sciences, University of Bristol, Bristol, United Kingdom, (27)Centre for Virology, University College London, London, United Kingdom, (28)Stanford University Division of Pediatric Infectious Disease, Palo Alto, CO, (29)Vanderbilt University Medical Center, Nashville, TN, (30)Pediatric Infectious Disease, University of Southern California, Los Angeles, CA, (31)Division of Pediatric Infectious Diseases, Emory University School of Medicine, Atlanta, GA, (32)St George's, University of London, London, United Kingdom, (33)Pediatrics, Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, (34)Pediatrics, LSUHSC-Shreveport, Shreveport, LA, (35)University of Alabama Birmingham, Birmingham, AL, (36)Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (37)Pediatric Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, PA

Disclosures:

D. W. Kimberlin, GSK: Grant Investigator, Grant recipient and I serve as one of dozens of sites on clinical trials conducted by GSK. All monies go directly to my university and not to me.
Giliead: Grant Investigator, Grant recipient and I serve as one of dozens of sites on clinical trials conducted by Gilead. All monies go directly to my university and not to me.

P. Jester, None

P. J. Sanchez, NIH: Grant Investigator, Research grant
Abvie: Scientific Advisor, Speaker honorarium
Glaxo-Smith-Kline: Grant Investigator, Research grant

A. Ahmed, None

R. Arav-Boger, None

S. Sood, None

C. Woods, Cerexa: Data Safety Monitoring Board member for pediatric clinical trials using ceftaroline, Payment for DSMB service
Pfizer: Research Contractor, Grant recipient

N. Ashouri, None

J. A. Englund, PIDS: Board Member, None
Chimerix: Investigator, Research support
Gilead: Investigator, Research support
Novartis: Investigator, Research support
GlaxoSmithKline: Consultant, Consulting fee

B. Estrada, None

R. Jacobs, None

J. R. Romero, None

S. Whitworth, None

M. J. Abzug, None

M. T. Caserta, None

S. Fowler, None

J. Lujan-Zilbermann, None

G. Storch, Roche Molecular Diagnostics: Consultant, Consulting fee
Primera Dx: Consultant, Consulting fee

R. W. Tolan Jr., None

R. Debiasi, None

J. Y. Han, None

A. Palmer, None

L. Weiner, None

J. Bocchini Jr., None

P. Dennehy, None

A. Finn, None

P. Griffiths, Genentech: Grant Investigator, Research support
Sanofi Pasteur: Collaborator, Research support
Astellas: Scientific Advisor, Research support

K. Gutierrez, None

N. Halasa, None

J. Homans, None

A. L. Shane, The Gerber Foundation: Grant Investigator, Research grant
Medscape, LLC: Speaker's Bureau, Speaker honorarium

M. Sharland, None

K. Simonsen, None

J. A. Vanchiere, None

I. Aban, None

E. Acosta, None

R. Whitley, None

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