Congenital Cytomegalovirus Infection
Conditions
Keywords
Cytomegalovirus, Pregnancy, CMVIG, maternal CMV infection
Brief summary
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).
Interventions
DRUGBT097
Subjects will receive BT097 200 U per kg of maternal body weight intravenously every 2 weeks until at least GW 17
Sponsors
Biotest
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the overall rate of maternal-fetal transmission at the time of amniocentesis (week 20 [-1 week / +2 weeks] of gestation) | Gestational week 19 - week 22 | To determine the overall rate of maternal-fetal transmission at the time of amniocentesis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine maternal CMV viral load (copies/ml) | until gestational week 30 | Number of CMV-DNA copies (copies/mL) and corresponding absolute and percentage changes from baseline, until gestational week (GW) 30 |
| To determine maternal anti-CMV IgG Levels (U/ml) | until gestational week 30 | Maternal anti-CMV IgG Levels (U/ml), absolute and percentage changes from baseline |
| To determine maternal anti-CMV IgG avidity (%) | until gestational week 30 | Number/percentage of subjects with Low, Intermediate, High avidity |
| To determine maternal anti-CMV IgM index (Index) | until gestational week 30 | Number/percentage of subjects with non-reactive, indeterminate and reactive cut-off index (COI) |
| To determine soluble fms-like tyrosine kinase 1 (sFlt-1) concentration in maternal serum | until gestational week 30 | Number/percentage of subjects with high (≥1504 pg/mL) or low (\<1504 pg/mL) values |
| Subgroups: (1) Subjects with periconceptionally acquired infection or (2) Subjects with infection acquired during first trimester | Gestational week 20 +-1 Week | To determine the rate of maternal-fetal transmission at the time of amniocentesis |
| To evaluate growth of the fetuses/newborns | Until date of delivery | Number/percentage of subjects with Normal / Abnormal Not Clinically Significant / Abnormal Clinically Significant results per parameter and visit |
| To evaluate the rate of congenital CMV infection at delivery or within the first 3 days after delivery | Date of Delivery + 3 days | To evaluate the rate of congenital CMV infection at delivery or within the first 3 days after delivery |
| To measure the number of CMV-DNA copies in the urine of newborns | Date of Delivery | To measure the number of CMV-DNA copies in the urine of newborns |
| 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 | 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 evaluate vitality of the fetuses/newborns | until date of delivery | Number/percentage of subjects with Normal / Abnormal Not Clinically Significant / Abnormal Clinically Significant results per parameter and visit |
Countries
Germany
Outcome results
None listed