Asymptomatic Congenital CMV Treatment
Condition: Congenital Cytomegalovirus Infection
MeSH terms: Infections; Cytomegalovirus Infections
Intervention: Valganciclovir
Intervention description: Valganciclovir, 16 mg/kg/dose given orally twice daily for four months
Intervention MeSH terms: Valganciclovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 1 Day
Maximum age: 30 Days
Healthy volunteers: No
Keywords: Asymptomatic; Congenital CMV Infection; Valganciclovir Therapy

Summary:

      This is a phase II, open-label trial to evaluate valganciclovir as a treatment to prevent
      development of sensorineural hearing loss (SNHL) in infants with asymptomatic congenital
      cytomegalovirus (CMV) infection. The trial will be conducted in two phases - screening of
      newborns to identify eligible subjects, and treatment of those newborns who have confirmed
      CMV infection at birth but without outward manifestations of congenital CMV infection. 229
      newborns with confirmed CMV infection but without baseline SNHL and who meet all
      inclusion/exclusion criteria will be enrolled into the treatment phase. Study duration is 5
      years. Primary objective of this study is to estimate the proportion of subjects with
      asymptomatic congenital CMV infection who, following treatment with 4 months of oral
      valganciclovir, develop SNHL by 6 months of life.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Parent(s)/legal guardian(s) have signed informed consent documents*

          -  Confirmation of cytomegalovirus (CMV) by urine polymerase chain reaction (PCR) testing

          -  Infant </= 30 days of age at initiation of study drug

          -  Weight at study enrollment >/= 1775 grams

          -  Gestational age >/= 32 weeks at birth

               -  There is a screening informed consent for screening phase of study participation,
                  and a treatment informed consent for treatment phase of study participation.

        Exclusion Criteria:

          -  Symptomatic congenital cytomegalovirus (CMV) disease*

          -  Sensorineural hearing deficits as detected by formal brainstem evoked response (not a
             screening auditory brainstem response (abr)) of known etiology other than CMV

          -  Prior or current receipt of ganciclovir, valganciclovir, foscarnet, cidofovir,
             brincidofovir, maribavir, or letermovir

          -  Maternal receipt of CMV hyperimmune globulin during pregnancy

          -  Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet,
             cidofovir, brincidofovir, maribavir, or letermovir

          -  Gastrointestinal abnormality which might preclude absorption of an oral medication
             (e.g., a history of necrotizing enterocolitis)

          -  Infants known to be born to women who are HIV positive (HIV testing is not required
             for study entry)

          -  Current receipt of other investigational drugs

               -  Symptomatic disease is defined as one or more of the following: 1)
                  thrombocytopenia, if known; 2) petechiae; 3) hepatomegaly; 4) splenomegaly; 5)
                  intrauterine growth restriction; 6) hepatitis (elevated transaminases and/or
                  direct bilirubin), if known; 7) central nervous system involvement of the CMV
                  disease (such as microcephaly; radiographic abnormalities indicative of CMV CNS
                  disease, if known; abnormal CSF indices for age, if known; chorioretinitis, if
                  known; and/or positive CMV PCR from CSF, if known).