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

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

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).

Study Overview

• Status: Terminated
• Conditions: Congenital Cytomegalovirus Infection
• Intervention / Treatment: Drug: BT097

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • 4906
  • Bonn, Germany, 53127
    • 4903
  • Erlangen, Germany, 91054
    • 4902
  • Tuebingen, Germany, 72076
    • 4901
  • Wasserburg am Inn, Germany, 83512
    • 4905

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biotest
• Investigators: Principal Investigator: Karl O Kagan, Prof, Universitätsklinik Tuebingen - Frauenklinik; 72076 Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2021
• Primary Completion (Actual): November 19, 2023
• Study Completion (Actual): March 29, 2024

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Cytomegalovirus; CMVIG; maternal CMV infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections
• Other Study ID Numbers: 997; 2020-002383-32 (EudraCT Number)

Drug and device information, study documents

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