Herpes Simplex VirusPhase 1/2NCT01610765
A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)
A Phase 1/2 study testing Novel Antiviral Drug in people with Herpes Simplex Virus, run by University of Alabama at Birmingham at 18 sites in United States.
Trial summary
This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug. Read more about this study
- Who is it for?
- Ages 1 day to 98 days
- Conditions the study is for
- Herpes Simplex Virus
- What is being tested?
- Novel Antiviral Drug
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 18 sitesUnited States
- Study dates
- Jan 2016to Jun 2017
- 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 1 day to 98 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed Informed Consent by parent or legal guardian of study subject
- Virologically confirmed HSV infection [e.g., positive culture, DNA detection by polymerase chain reaction (PCR), or direct fluorescent antibody stain from any body site or compartment]
- Evidence of CNS involvement of HSV disease [e.g., CSF pleocytosis, positive CSF PCR testing, clinical or electroencephalogram (EEG) seizure activity, neuroimaging abnormality)
- Starting parenteral acyclovir therapy at time of initiation of CMX001 study drug or receiving parenteral acyclovir therapy for ≤ 72 hours before start CMX001 study drug
- ≤ 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs
- Weight at study enrollment ≥ 2,630 grams
- Gestational age ≥ 36 weeks at delivery
- Mother tested negative for HIV during or following pregnancy
Who cannot join
- Imminent demise
- Disseminated or skin/eye/mouth (SEM) neonatal HSV disease classifications
- Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., history of necrotizing enterocolitis, gastroschisis, malrotation, etc.)
- Birth weight < 2,500 grams
- Birth weight > 4,500 grams
- Grade 3 or 4 vomiting, utilizing the DAIDS Toxicity Tables (Appendix B)
Show all 19Show fewer
- Grade 3 or 4 diarrhea, utilizing the DAIDS Toxicity Tables (Appendix B)
- Creatinine clearance < 15 mL/min/1.73m2
- Serum albumin < 2.0 g/dL
- Alanine aminotransferase (ALT) ≥ 2.6-times upper limit normal (ULN)
- Aspartate aminotransferase (AST) ≥ 2.6-times upper limit normal (ULN)
- Direct bilirubin > 2 mg/dL
- Known immunodeficiency
- Known congenital infection (e.g., symptomatic congenital cytomegalovirus infection; syphilis; congenital toxoplasmosis)
- Congenital heart disease (e.g., patent ductus arteriosus, Tetralogy of Fallot, hypoplastic left heart syndrome, AV canal, VSD, ASD, transposition of the great arteries, hypoplastic right ventricle, truncus arteriosus, pulmonic stenosis, Ebstein anomaly, coarctation of the aorta, interrupted aortic arch, double outlet right ventricle, dilated cardiomyopathy)
- Infants currently receiving or anticipated to need treatment with digoxin that cannot be withheld for the duration of CMX001 therapy
- Infants currently receiving or anticipated to need treatment with ketaconazole that cannot be withheld for the duration of CMX001 therapy
- Receipt of investigation drugs within 30 days prior to enrollment
- Concurrent enrollment or participation in any other interventional research study
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Emory Children's Center
Atlanta, Georgia, 30322
University of Colorado at Denver Health Sciences Center
Aurora, Colorado, 80045
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Carolinas Medical Center - Charlotte
Charlotte, North Carolina, 28203
MetroHealth Medical Center
Cleveland, Ohio, 44109
University of Texas-Southwestern
Dallas, Texas, 75390-9063
Dartmouth Medical School
Lebanon, New Hampshire, 03756
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72202
Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC)
Manhasset, New York, 11030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-2581
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Rhode Island Hospital
Providence, Rhode Island, 02903
University of Rochester Medical Center
Rochester, New York, 14642
University of Utah School of Medicine
Salt Lake City, Utah, 84132
Louisiana State University Health Science Center -Shreveport
Shreveport, Louisiana, 71103
Washington University in St Louis School of Medicine
St Louis, Missouri, 63110
University of South Florida School of Medicine
Tampa, Florida, 33606
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug.
Read the detailed description
In this study, the pharmacokinetics and safety of a Novel Antiviral Drug will be determined in babies with neonatal HSV CNS disease. The study will be conducted at 18 academic medical centers throughout the United States. Young infants presenting with virologic confirmation of neonatal HSV infection and evidence of CNS involvement will be eligible for study enrollment. Study Day 1 is defined as the day when dose 1 of the Novel Antiviral Drug study medication is administered.
- Conditions
- Herpes Simplex Virus
- Being tested
- Novel Antiviral Drug, Placebo
- Keywords
- HSV, pharmacokinetics, herpes, neonates
- Medical subject headings
- Herpes Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Novel Antiviral DrugDrug
4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.
PlaceboDrug
4 oral doses of placebo matching the a Novel Antiviral Drug assigned dose: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.
| Study group | Role | What they receive |
|---|---|---|
| Novel Antiviral Drug | Active comparator | Subjects will be randomized to receive one of 3 oral doses of a Novel Antiviral Drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered Receives: Drug: Novel Antiviral Drug |
| Placebo | Placebo comparator | Subjects will be randomized to receive one of 3 oral doses of placebo matched in volume to active drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
Measured: Baseline through day 21
Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
Measured: Baseline through day 21
Secondary outcomes (2)
Explore a plasma drug concentration-response relationship between CMX001 exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
Measured: Baseline through day 21
Explore a plasma drug concentration-response relationship between cidofovir exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
Measured: Baseline through day 56 (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2012 (estimated)
- Study startJan 2016
- Primary completionJun 2017 (estimated)
- Study completionJun 2017 (estimated)
Why it stopped: Study terminated because unable to obtain access to study drug for study population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Herpes Simplex VirusStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Kimberlin, MD, University of Alabama at Birmingham
- Investigators
- David W Kimberlin, MD, Principal investigator, University of Alabama at BirminghamRichard Whitley, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610765
- Sponsor's protocol ID
- DMID 11-0068
- Status last verified
- Jun 2016
- First submitted
- 30 May 2012
- Last updated
- 7 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)
- ClinicalTrials.gov ID
- NCT01610765
- Acronym / sponsor ID
- DMID 11-0068
- Conditions
- Herpes Simplex Virus
- Keywords
- HSV, pharmacokinetics, herpes, neonates
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study terminated because unable to obtain access to study drug for study population.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Jan 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 4 Jun 2012 (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.
This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug.
Detailed description
In this study, the pharmacokinetics and safety of a Novel Antiviral Drug will be determined in babies with neonatal HSV CNS disease. The study will be conducted at 18 academic medical centers throughout the United States. Young infants presenting with virologic confirmation of neonatal HSV infection and evidence of CNS involvement will be eligible for study enrollment. Study Day 1 is defined as the day when dose 1 of the Novel Antiviral Drug study medication is administered.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Novel Antiviral Drug | Active comparator | Drug: Novel Antiviral DrugSubjects will be randomized to receive one of 3 oral doses of a Novel Antiviral Drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to receive one of 3 oral doses of placebo matched in volume to active drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered |
Who may qualify
- Ages
- 1 day to 98 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Signed Informed Consent by parent or legal guardian of study subject
- Virologically confirmed HSV infection [e.g., positive culture, DNA detection by polymerase chain reaction (PCR), or direct fluorescent antibody stain from any body site or compartment]
- Evidence of CNS involvement of HSV disease [e.g., CSF pleocytosis, positive CSF PCR testing, clinical or electroencephalogram (EEG) seizure activity, neuroimaging abnormality)
- Starting parenteral acyclovir therapy at time of initiation of CMX001 study drug or receiving parenteral acyclovir therapy for ≤ 72 hours before start CMX001 study drug
- ≤ 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs
Key exclusion criteria (19 listed)
- Imminent demise
- Disseminated or skin/eye/mouth (SEM) neonatal HSV disease classifications
- Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., history of necrotizing enterocolitis, gastroschisis, malrotation, etc.)
- Birth weight < 2,500 grams
- Birth weight > 4,500 grams
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 |
|---|---|---|
| Novel Antiviral Drug4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level. | Drug | Novel Antiviral Drug |
| Placebo4 oral doses of placebo matching the a Novel Antiviral Drug assigned dose: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level. | Drug | Placebo |
Primary outcome
Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
Time frame: Baseline through day 21
Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
Time frame: Baseline through day 21
2 secondary outcomes
Explore a plasma drug concentration-response relationship between CMX001 exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
Time frame: Baseline through day 21
Explore a plasma drug concentration-response relationship between cidofovir exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
Time frame: Baseline through day 56 (end of study)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2016.
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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.
David W Kimberlin, MD principal investigator
University of Alabama at Birmingham
Richard Whitley, MD principal investigator
University of Alabama at Birmingham
18 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 Novel Antiviral Drug in people with Herpes Simplex Virus, run by University of Alabama at Birmingham at 18 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 8 inclusion and 19 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: withdrawn, as of the sponsor's last update on 7 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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?
Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease. (time frame: Baseline through day 21). The study lists 2 primary outcomes in all. 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 Jun 2016.