Prevention of Maternal-fetal Cytomegalovirus Transmission After Primary Maternal Infection, GW ≤ 14 (PreCyssion)

Study Overview
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Brief Summary
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A phase 3, open-label, single-arm, prospective, multi-center trial of Cytotect CP Biotest (BT097) for prevention of maternal-fetal CMV transmission after primary maternal CMV infection. The main purpose of the trial is to demonstrate efficacy and safety of Cytotect CP Biotest in preventing maternal-fetal transmission of cytomegalovirus (CMV).

Official Title
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Prevention of Maternal-fetal Cytomegalovirus Transmission After Primary Maternal Infection With Gestational Age ≤ 14 Weeks - an Open-label, Single-arm, Prospective Trial Investigating Efficacy and Safety of Cytotect CP Biotest

Conditions
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Congenital Cytomegalovirus Infection

Intervention / Treatment
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* Drug: BT097


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from subjects indicating that they understand the purpose of and procedures required for the trial and are willing to participate in it Pregnant women, age 18 to 45 years Pregnant women at trial entry with gestational age ≤14 weeks; pregnancy after in-vitro fertilization permitted Detection of early primary CMV infection Exclusion Criteria: Women with current multiple pregnancy History of severe pre-eclampsia or severe gestational hypertension (GHTN), which required medical intervention. Definition according to AWMF guideline (AWMF, 2019) Presence of severe disease impairing course of pregnancy (e.g. diabetes, epilepsy, cancer) Congenital or acquired autoimmune disease Known immunosuppressive (e.g., transplanted patients) or immunodeficient condition Known infection with hepatitis B or C, or HIV from the medical history or active infection at screening as assessed by respective virus serology Maternal CMV infection prior to this pregnancy (preconceptional CMV infection) Covid-19 infection at time of inclusion Any signs or symptoms indicating an increased risk of abortion or premature labor or has known negative effect on fetus with exception of a CMV infection Active infection according to TORCH serology with exception of CMV in the assessment of the investigator Known major fetal anomalies or demise Intolerance to proteins of human origin or known allergic reactions to components of the trial product Selective absolute IgA deficiency or known antibodies to IgA Known pre-existing clinically relevant risk factors for thrombotic events Known renal insufficiency with serum creatinine levels >1.4 mg/dL and proteinuria (albuminuria) at screening (≥30 mg/dL or dipstick reading of 1+ and greater) Participation in another clinical trial within 90 days before entering the trial or during the trial Women who are dependent on trial site staff, on Biotest AG or its authorized representatives Inability or lacking motivation to participate in the trial Medical condition, laboratory finding, or physical examination finding that in the opinion of the investigator precludes participationInability or lacking motivation to participate in the trial Eligibility for a subgroup where enrollment was stopped

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BT097<br>Subjects will receive BT097 200 U per kg of maternal body weight intravenously every 2 weeks until at least GW 17 | Drug: BT097<br>* Subjects will receive BT097 200 U per kg of maternal body weight intravenously every 2 weeks until at least GW 17<br>* Other names: Cytotect CP Biotest 100 U/mL solution for infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the overall rate of maternal-fetal transmission at the time of amniocentesis (week 20 [-1 week / +2 weeks] of gestation) | To determine the overall rate of maternal-fetal transmission at the time of amniocentesis | Gestational week 19 - week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subgroups: (1) Subjects with periconceptionally acquired infection or (2) Subjects with infection acquired during first trimester | To determine the rate of maternal-fetal transmission at the time of amniocentesis | Gestational week 20 +-1 Week | 
| To determine maternal CMV viral load (copies/ml) | Number of CMV-DNA copies (copies/mL) and corresponding absolute and percentage changes from baseline, until gestational week (GW) 30 | until gestational week 30 | 
| To determine maternal anti-CMV IgG Levels (U/ml) | Maternal anti-CMV IgG Levels (U/ml), absolute and percentage changes from baseline | until gestational week 30 | 
| To determine maternal anti-CMV IgG avidity (%) | Number/percentage of subjects with Low, Intermediate, High avidity | until gestational week 30 | 
| To determine maternal anti-CMV IgM index (Index) | Number/percentage of subjects with non-reactive, indeterminate and reactive cut-off index (COI) | until gestational week 30 | 
| To determine soluble fms-like tyrosine kinase 1 (sFlt-1) concentration in maternal serum | Number/percentage of subjects with high (≥1504 pg/mL) or low (<1504 pg/mL) values | until gestational week 30 | 
| To evaluate vitality of the fetuses/newborns | Number/percentage of subjects with Normal / Abnormal Not Clinically Significant / Abnormal Clinically Significant results per parameter and visit | until date of delivery | 
| To evaluate growth of the fetuses/newborns | Number/percentage of subjects with Normal / Abnormal Not Clinically Significant / Abnormal Clinically Significant results per parameter and visit | Until date of delivery | 
| To evaluate the rate of congenital CMV infection at delivery or within the first 3 days after delivery | To evaluate the rate of congenital CMV infection at delivery or within the first 3 days after delivery | Date of Delivery + 3 days | 
| To measure the number of CMV-DNA copies in the urine of newborns | To measure the number of CMV-DNA copies in the urine of newborns | Date of Delivery | 
| To assess the number, severity, causality, outcome, and seriousness of all adverse events (AEs)/ treatment-emergent AEs (TEAEs)/ AEs of special interest until delivery (+3 days) in both mother and fetus/newborn | To assess the number, severity, causality, outcome, and seriousness of all adverse events (AEs)/ treatment-emergent AEs (TEAEs)/ AEs of special interest until delivery (+3 days) in both mother and fetus/newborn | Date of Delivery + 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytomegalovirus, Pregnancy, CMVIG, maternal CMV infection