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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: HCMV Infection
• Intervention / Treatment: Biological: CSJ148; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Pregnant women ≥ 18 years of age with primary HCMV infection occurring between 6 and 24 weeks of gestation
3. Ability to receive study drug within 6 weeks of the presumed onset of primary maternal infection.
4. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion Criteria:

1. Confirmed or suspected fetal HCMV infection, defined as positive HCMV DNA in amniotic fluid or fetal ultrasound abnormalities suggestive of fetal HCMV disease.
2. 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.
3. 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.
4. History of chronic hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infection. Cured hepatitis C in not considered exclusionary.
5. Patient request for medical interruption or termination of pregnancy before inclusion.
6. 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.
7. 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.
8. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes.
9. Body weight > 100 kilograms.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; CSJ148	Biological: CSJ148; Active
Placebo Comparator: Placebo; 5% dextrose	Other: Placebo; No Drug

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): October 23, 2018
• Primary Completion (Anticipated): November 15, 2022
• Study Completion (Anticipated): November 15, 2022

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: pregnant women; Safety, efficacy; CSJ148; HCMV infection; congenital HCMV
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections
• Other Study ID Numbers: CCSJ148X2202; 2017-002047-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No