Cytomegalovirus InfectionsPhase 1/2NCT00031434
Valganciclovir in Congenital CMV Infants
A Phase 1/2 study testing Valganciclovir and Ganciclovir in people with Cytomegalovirus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in United States.
Trial summary
The purpose of this study is to evaluate how ganciclovir is metabolized when administered intravenously (by a needle inserted into a vein) following valganciclovir syrup, given by mouth to newborns and young infants with symptoms of congenital (present at birth) cytomegalovirus (CMV) disease. Read more about this study
- Who is it for?
- Ages Up to 30 days
- Conditions the study is for
- Cytomegalovirus Infections
- What is being tested?
- Valganciclovir and Ganciclovir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 21 sitesUnited States
- Study dates
- Jul 2002to Jul 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed informed consent from parent(s) or legal guardian(s).
- Culture confirmation of cytomegalovirus (CMV) from urine or throat swab specimens.
- Symptomatic congenital CMV disease, as manifest by one or more of the following:
- Thrombocytopenia Petechiae Hepatomegaly Splenomegaly Intrauterine growth restriction Hepatitis (elevated transaminases and/or bilirubin) Central nervous system involvement of the CMV disease (such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal CSF indices for age, chorioretinitis, hearing deficits as detected by brainstem evoked response, and/or positive CMV PCR from CSF)
- Less than or equal to 30 days of age at study enrollment.
- Weight at study enrollment greater than or equal to 1800 grams.
- Gestational age greater than or equal to 32 weeks.
Who cannot join
- Imminent demise.
- Patients receiving other antiviral agents or immune globulin.
- Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis).
- Creatinine clearance < 10mL/min/1.73 square meters at time of study enrollment.
- Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Medical University of South Carolina
Charleston, South Carolina, 29425
Stroger Cook Hospital
Chicago, Illinois, 60612
MetroHealth Medical Center
Cleveland, Ohio, 44109-1998
Ohio State University
Columbus, Ohio, 43205
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390-9063
Cook Children's Medical Center
Fort Worth, Texas, 76104
The University of Texas Medical Branch
Galveston, Texas, 77555
University of Florida
Jacksonville, Florida, 32209
University of Arkansas
Little Rock, Arkansas, 72202-3591
University of Southern California
Los Angeles, California, 90033
University of Louisville
Louisville, Kentucky, 40202-3830
Schneider Children's Hospital
Manhasset, New York, 11030
Tulane University
New Orleans, Louisiana, 70112
Creighton University
Omaha, Nebraska, 68198-2162
Children's Hospital of Orange County
Orange, California, 92868
The University of Texas Health Science Center
San Antonio, Texas, 78229
Washington University in St. Louis
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
Official title: A Phase I/II Pharmacokinetic and Pharmacodynamic Evaluation of Oral Valganciclovir in Neonates With Symptomatic Congenital Cytomegalovirus (CMV) Infection (CASG 109)
The purpose of this study is to evaluate how ganciclovir is metabolized when administered intravenously (by a needle inserted into a vein) following valganciclovir syrup, given by mouth to newborns and young infants with symptoms of congenital (present at birth) cytomegalovirus (CMV) disease. The study also seeks to identify a dose of valganciclovir that provides a comparable blood concentration to ganciclovir present in the blood of newborns with symptomatic congenital CMV disease. All study participants will receive 6 weeks of antiviral therapy (defined as ganciclovir and/or valganciclovir). Infants from 0 to 30 days old will participate in the study for 2 years.
Read the detailed description
Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system results in improved hearing function (or maintenance of normal hearing function) and prevents hearing deterioration at 6 months. Furthermore, ganciclovir therapy may prevent hearing deterioration at 1 year. Ganciclovir recipients also have a more rapid resolution of their transaminase elevations and a greater degree of short term growth in weight and head circumference compared with untreated patients. Valganciclovir, the oral product of ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat longer, but pharmacokinetic data are needed in infants first to assure the correct dose is being utilized. This Phase I/II, multi-center, open-label trial will assess the safety/tolerability and pharmacokinetics (ganciclovir concentrations) following administration of oral valganciclovir to neonates with symptomatic congenital CMV disease. A total of 24 patients will be evaluated. All patients entered into this study will receive 6 weeks (42 days) of antiviral therapy (defined as ganciclovir and/or valganciclovir). Two different dose determination strategies will be applied in this protocol. The first is an individual patient approach. The second is a group dose modification strategy. The primary endpoint is pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis. Secondary endpoints are: the pharmacokinetics of valganciclovir following administration of oral valganciclovir; the correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load; lack of vomiting and/or diarrhea associated with the administration of oral valganciclovir syrup; and assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.
- Conditions
- Cytomegalovirus Infections
- Being tested
- Valganciclovir, Ganciclovir
- Keywords
- Valganciclovir, congenital cytomegalovirus, ganciclovir
- Medical subject headings
- Cytomegalovirus Infections, Multiple Acyl Coenzyme A Dehydrogenase Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValganciclovirDrug
Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir oral syrup formulation for administration will be provided as a 15g powder blend containing 3g valganciclovir base, for constitution in 120 mL amber glass bottles. The beginning oral valganciclovir dose under investigation is 14 mg/kg. The dose of oral valganciclovir syrup will be adjusted for the baby's weight and renal function. Weights upon which dosage will be adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35.
GanciclovirDrug
Ganciclovir for intravenous infusion will be provided as sterile, lyophilized powder in sealed vials containing 500 mg ganciclovir for re-constitution. The dose of intravenous ganciclovir is 6 mg/kg. Intravenous ganciclovir will be adjusted for the baby's weight and renal function. Weights upon which dosage adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. Each dose of intravenous ganciclovir should be given over 1 hour using an intravenous pump.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | All subjects enrolled into this study will receive 6 weeks (42 days) of antiviral therapy (valganciclovir/ganciclovir). Receives: Drug: Valganciclovir; Drug: Ganciclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis.
Measured: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. Day 3: with 2nd dose of IV ganciclovir, before dose, 1 hour, 2-3, 5-7, and 10-12 hours after dose. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK.
Secondary outcomes (4)
Pharmacokinetics of valganciclovir following administration of oral valganciclovir syrup.
Measured: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK.
Lack of vomiting and/or diarrhea associated with administration of oral valganciclovir syrup.
Measured: Assessed through Day 56.
Correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load.
Measured: Day 1 (prior to dose 1 of valganciclovir), Day 7, Day 14, Day 28, Day 42, Day 56, and 6 months.
Assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.
Measured: Duration of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2002 (estimated)
- Study startJul 2002
- Primary completionJul 2007
- Study completionJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00031434
- Sponsor's protocol ID
- 01-595
- Other IDs
- CASG 109
- Status last verified
- Jul 2009
- First submitted
- 6 Mar 2002
- Last updated
- 7 Feb 2011
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Pharmacokinetic and Pharmacodynamic Evaluation of Oral Valganciclovir in Neonates With Symptomatic Congenital Cytomegalovirus (CMV) Infection (CASG 109)
- ClinicalTrials.gov ID
- NCT00031434
- Acronym / sponsor ID
- 01-595
- Conditions
- Cytomegalovirus Infections
- Keywords
- Valganciclovir, congenital cytomegalovirus, ganciclovir
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jul 2002
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 7 Mar 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate how ganciclovir is metabolized when administered intravenously (by a needle inserted into a vein) following valganciclovir syrup, given by mouth to newborns and young infants with symptoms of congenital (present at birth) cytomegalovirus (CMV) disease. The study also seeks to identify a dose of valganciclovir that provides a comparable blood concentration to ganciclovir present in the blood of newborns with symptomatic congenital CMV disease. All study participants will receive 6 weeks of antiviral therapy (defined as ganciclovir and/or valganciclovir). Infants from 0 to 30 days old will participate in the study for 2 years.
Detailed description
Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system results in improved hearing function (or maintenance of normal hearing function) and prevents hearing deterioration at 6 months. Furthermore, ganciclovir therapy may prevent hearing deterioration at 1 year. Ganciclovir recipients also have a more rapid resolution of their transaminase elevations and a greater degree of short term growth in weight and head circumference compared with untreated patients. Valganciclovir, the oral product of ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat longer, but pharmacokinetic data are needed in infants first to assure the correct dose is being utilized. This Phase I/II, multi-center, open-label trial will assess the safety/tolerability and pharmacokinetics (ganciclovir concentrations) following administration of oral valganciclovir to neonates with symptomatic congenital CMV disease. A total of 24 patients will be evaluated. All patients entered into this study will receive 6 weeks (42 days) of antiviral therapy (defined as ganciclovir and/or valganciclovir). Two different dose determination strategies will be applied in this protocol. The first is an individual patient approach. The second is a group dose modification strategy. The primary endpoint is pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis. Secondary endpoints are: the pharmacokinetics of valganciclovir following administration of oral valganciclovir; the correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load; lack of vomiting and/or diarrhea associated with the administration of oral valganciclovir syrup; and assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Valganciclovir, Drug: GanciclovirAll subjects enrolled into this study will receive 6 weeks (42 days) of antiviral therapy (valganciclovir/ganciclovir). |
Who may qualify
- Ages
- Up to 30 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Signed informed consent from parent(s) or legal guardian(s).
- Culture confirmation of cytomegalovirus (CMV) from urine or throat swab specimens.
- Symptomatic congenital CMV disease, as manifest by one or more of the following:
- Thrombocytopenia Petechiae Hepatomegaly Splenomegaly Intrauterine growth restriction Hepatitis (elevated transaminases and/or bilirubin) Central nervous system involvement of the CMV disease (such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal CSF indices for age, chorioretinitis, hearing deficits as detected by brainstem evoked response, and/or positive CMV PCR from CSF)
- Less than or equal to 30 days of age at study enrollment.
Key exclusion criteria (5 listed)
- Imminent demise.
- Patients receiving other antiviral agents or immune globulin.
- Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis).
- Creatinine clearance < 10mL/min/1.73 square meters at time of study enrollment.
- Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValganciclovirValganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir oral syrup formulation for administration will be provided as a 15g powder blend containing 3g valganciclovir base, for constitution in 120 mL amber glass bottles. The beginning oral valganciclovir dose under investigation is 14 mg/kg. The dose of oral valganciclovir syrup will be adjusted for the baby's weight and renal function. Weights upon which dosage will be adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. | Drug | 1 |
| GanciclovirGanciclovir for intravenous infusion will be provided as sterile, lyophilized powder in sealed vials containing 500 mg ganciclovir for re-constitution. The dose of intravenous ganciclovir is 6 mg/kg. Intravenous ganciclovir will be adjusted for the baby's weight and renal function. Weights upon which dosage adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. Each dose of intravenous ganciclovir should be given over 1 hour using an intravenous pump. | Drug | 1 |
Primary outcome
Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis.
Time frame: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. Day 3: with 2nd dose of IV ganciclovir, before dose, 1 hour, 2-3, 5-7, and 10-12 hours after dose. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK.
4 secondary outcomes
Pharmacokinetics of valganciclovir following administration of oral valganciclovir syrup.
Time frame: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK.
Lack of vomiting and/or diarrhea associated with administration of oral valganciclovir syrup.
Time frame: Assessed through Day 56.
Correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load.
Time frame: Day 1 (prior to dose 1 of valganciclovir), Day 7, Day 14, Day 28, Day 42, Day 56, and 6 months.
Assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.
Time frame: Duration of study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Valganciclovir and Ganciclovir in people with Cytomegalovirus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis. (time frame: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. Day 3: with 2nd dose of IV ganciclovir, before dose, 1 hour, 2-3, 5-7, and 10-12 hours after dose. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2011.