A Study to Evaluate CSJ148 in Pregnant Women With Primary HCMV Infection

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the feasibility of using CSJ148 to prevent congenital human cytomegalovirus (HCMV) in pregnant women with primary HCMV infection.

Detailed Description
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This is a randomized, patient, investigator and sponsor blinded, placebo-controlled study in pregnant women with primary HCMV infection. The study has three periods: (I) screening (II) double-blinded placebo-controlled treatment and (III) post-delivery follow-up of women and neonates/infants. Pregnant women with confirmed primary HCMV infection will participate in periods I and II. Mothers and neonates/infants born to mothers enrolled in the study will participate in period III.

Official Title
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A Multicenter, Randomized, Patient, Investigator and Sponsor Blinded, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of CSJ148 in Pregnant Women With Primary HCMV Infection

Conditions
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HCMV Infection

Intervention / Treatment
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* Biological: CSJ148
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Pregnant women ≥ 18 years of age with primary HCMV infection occurring between 6 and 24 weeks of gestation Ability to receive study drug within 6 weeks of the presumed onset of primary maternal infection. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Exclusion Criteria: Confirmed or suspected fetal HCMV infection, defined as positive HCMV DNA in amniotic fluid or fetal ultrasound abnormalities suggestive of fetal HCMV disease. Prior treatment with any of the following within 30 days prior to enrollment: ganciclovir, valganciclovir, foscarnet, cidofovir, acyclovir (>25 mg/kg/day IV), valacyclovir (>3 gm/day oral), famciclovir (>1500 mg/day oral), HCMV immune globulin, immune globulin (>500 mg/kg), or any other medication with anti-HCMV activity. Any surgical or medical condition (other than pregnancy) which might increase the risk for thrombotic events if the patient is given immune-globulins. These conditions include cryoglobulinemia, monoclonal gammopathies, and hypertriglyceridemia (fasting level >1000 mg/dL). The investigator should make this determination based on the patient's medical history and laboratory data. History of chronic hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infection. Cured hepatitis C in not considered exclusionary. Patient request for medical interruption or termination of pregnancy before inclusion. Any surgical or medical condition which may jeopardize the patient or fetus in case of participation in the study. The investigator should make this determination in consideration of the patient's obstetrical history. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes. Body weight > 100 kilograms.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, patient, investigator and sponsor blinded, placebo-controlled study in pregnant women with primary HCMV infection. This study is a non-confirmatory trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>CSJ148 | Biological: CSJ148<br>* Active<br>|
| Placebo Comparator: Placebo<br>5% dextrose | Other: Placebo<br>* No Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event rate of fetuses or neonates with congenital human cytomegalovirus (HCMV) infection | To assess the efficacy of CSJ148 on reducing intrauterine HCMV transmission compared to placebo | Day 218 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Reduction in symptomatic congenital human cytomegalovirus (HCMV) disease (compared to placebo) | Change in symptomatic HCMV disease, assessed by event rates in patients vs controls | Day 218 | 
| Change from baseline in congenital human cytomegalovirus (HCMV) urine viral load in neonates at birth | Change in HCMV urine viral load in neonates at birth | Baseline, Day 218 | 
| Pharmacokinetic concentration data of CSJ148 | Concentration of CSJ148 (LJP538 and LJP539) in serum | Days 1,29,57,85,218,141,169, 197, 218 | 
| CSJ148 concentration in cord blood | Concentration of CSJ148 (LJP538 and LJP539) in serum separated from cord blood | Day 218 | 
| Immunogenicity of CSJ148 in pregnant women | Detection of anti-LJP538 and anti-LJP539 antibodies in serum at selected timepoints | Days 1,29,57,85,218,141,169, 197, 218 | 
| Immunogenicity of CSJ148 in cord blood | Detection of anti-LJP538 and anti-LJP539 antibodies in serum from cord blood | Day 218 | 
| CSJ148 concentration in amniotic fluid | Concentration of CSJ148 (LJP538 and LJP539) in amniotic fluid | Day 218 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, efficacy, pregnant women, CSJ148, HCMV infection, congenital HCMV