Human Anti-D (rh) Immunoglobulin (Rhesoglobin) Efficacy, Safety and Some Pharmacokinetics Parameters in Pregnant Women

Open-label, Multicenter, International Study of the Efficacy and Safety of the Drug Rhesoglobin (Human Anti-D (rh) Immunoglobulin) Manufactured by Biopharma Plasma LLC, Ukraine, in Pregnant Women in the Antenatal and Postnatal Period in Routine Clinical Practice for the Prevention of Rh Sensitization, With a Subgroup for Evaluation of Some Pharmacokinetic Parameters

Rhesus conflict between mother and fetus is due to the different antigenic composition of erythrocytes. During the first pregnancy, sensitization of the mother to fetal erythrocytes rhesus D (RhD) antigens is formed. During the next pregnancy, fetal red blood cells are attacked by the mother's antibodies, and fetal/newborn hemolytic disease develops. The drug Rhesoglobin blocks the interaction of the fetal erythrocytes RhD antigen and the immune system of the mother and prevents the development of Rhesus sensitization.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Related
• Intervention / Treatment: Drug: Human Anti-D (rh) immunoglobulin

Detailed Description

The screening stage The pregnant woman (participant) has to sign an informed consent. After the signed informed consent procedure, the patient is assessed for meeting the inclusion and non-inclusion (exclusion) criteria. Patients who were included in the study are assessed according to additional criteria for inclusion in the "Pharmacokinetics" subgroup.

The clinical stage

According to the study protocol, patients receive two prophylactic doses of the study drug at a dose of 300 mcg - at 28 weeks of gestation and within 72 hours after delivery. Patients receive the second dose only in the case of the birth of an Rh-positive child. Before and after each injection of the drug, blood will be taken to control the level of anti-Rh0 (D) antibodies. In the "Pharmacokinetics" subgroup, additional blood samples will be taken to determine the following pharmacokinetic parameters:

• Serum clearance
• Volume of distribution
• AUC (area under curve)
• Т1/2 (α and β) (half-life time)
• Cmax (maximum/peak serum concentration)
• Tmax (time to reach the maximum serum concentration)
• Kel (elimination rate constant)

The final stage The patient should be monitored for 6 months ± 5 days, after the last injection of the drug, blood samples are taken after 3 and 6 months to assess sensitization to the Rh antigen.

• Study Type: Interventional
• Enrollment (Estimated): 281
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yaroslav Zhebelenko, Ph.D., MD; Phone Number: +380977495979; Email: y.zhebelenko@biopharma.ua
• Study Contact Backup: Name: Iryna Stavna; Email: i.stavna@biopharma.ua

Study Locations

• Ukraine
  • Chernihiv, Ukraine, 14000
    • Not yet recruiting
    • Municipal non-profit enterprise "Maternity hospital" of the Chernihiv city council
    • Contact: Olena Trykashna
    • Principal Investigator: Olena Trykashna
    • Sub-Investigator: Vasyl Husak
    • Sub-Investigator: Ivan Lysenko
  • Chernivtsi, Ukraine, 58000
    • Recruiting
    • Municipal non-profit enterprise "Chernivtsi Regional Perinatal Center"
    • Contact: Vasyl Rynzhuk, Ph.D
    • Principal Investigator: Vasyl Rynzhuk, Ph.D
    • Sub-Investigator: Svitlana Koliandretska
    • Sub-Investigator: Natalia Bukh
  • Dnipro, Ukraine, 49100
    • Not yet recruiting
    • Municipal enterprise "Dnipropetrovsk Regional Perinatal Center (DRPC) with a hospital" of the Dnipropetrovsk Regional Council
    • Contact: Olha Maltseva, Ph.D.
    • Principal Investigator: Olha Maltseva, Ph.D.
    • Sub-Investigator: Oksana Shchyrova, Professor
    • Sub-Investigator: Olena Zaiats
  • Ivano-Frankivsk, Ukraine, 76000
    • Recruiting
    • Municipal non-profit enterprise "Ivano-Frankivsk Regional Perinatal Center Ivano-Frankivsk Regional Council"
    • Contact: Oksana Makarchuk
    • Principal Investigator: Oksana Makarchuk
    • Sub-Investigator: Volodymyr Liubinets
    • Sub-Investigator: Andrii Cheredarchuk
  • Khmelnytskyi, Ukraine, 29013
    • Recruiting
    • Municipal non-profit enterprise "Khmelnytsky Regional Hospital" of the Khmelnytsky Regional Council
    • Contact: Olha Pukhliakova
    • Principal Investigator: Olha Pukhliakova
    • Sub-Investigator: Olena Malysh
    • Sub-Investigator: Anna Zholkevska
  • Kropyvnytskyi, Ukraine, 25000
    • Recruiting
    • Municipal non-profit enterprise "Kirovohrad Regional Hospital of the Kirovohrad Regional Council"
    • Contact: Tetiana Mitieva
    • Principal Investigator: Tetiana Mitieva
    • Sub-Investigator: Oksana Sliusarenko
  • Kyiv, Ukraine, 04050
    • Recruiting
    • State Institution "Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova National Academy of Medical Sciences of Ukraine "
    • Contact: Nataliia Skrypchenko, Ph.D., MD
    • Principal Investigator: Nataliia Skrypchenko, Ph.D., MD
    • Sub-Investigator: Viktoriia Fatiuk, Ph.D
    • Sub-Investigator: Oleksandra Khokhlova
  • Kyiv, Ukraine, 04210
    • Recruiting
    • Kyiv City Center for Reproductive and Perinatal Medicine
    • Contact: Shalko Myroslava, Ph.D.
    • Principal Investigator: Vyacheslav Kaminsky, Professor
    • Sub-Investigator: Shalko Myroslava, Ph.D.
  • Luts'k, Ukraine, 43008
    • Recruiting
    • Municipal enterprise "Volyn Regional Territorial Medical Association for the Protection of Motherhood and Childhood" Volyn Regional Council
    • Contact: Nadiia Shchuruk, Ph.D
    • Principal Investigator: Nadiia Shchuruk
    • Sub-Investigator: Anna Khoronzhuk
  • Lviv, Ukraine, 79032
    • Recruiting
    • Municipal non-profit enterprise Lviv Regional Council "Lviv Regional Clinical Perinatal Center"
    • Contact: Mariia Malachynska, Ph.D
    • Principal Investigator: Mariia Malachynska, Ph.D
    • Sub-Investigator: Natalia Veresniuk, Ph.D
    • Sub-Investigator: Anzhela Misiura, Ph.D, docent
  • Mykolayiv, Ukraine, 54058
    • Not yet recruiting
    • Municipal non-profit enterprise "Mykolayiv regional clinical hospital" of the Mykolayiv regional council
    • Contact: Oleh Kandaurov
    • Principal Investigator: Oleh Kandaurov
    • Sub-Investigator: Kateryna Tivon
    • Principal Investigator: Anzhelika Liubimova
  • Poltava, Ukraine, 36000
    • Not yet recruiting
    • Municipal enterprise "Poltava Regional Clinical Hospital named after M.V. Sklifosovsky Poltava regional council"
    • Contact: Viktoriia Vashchenko
    • Principal Investigator: Viktoriia Vashchenko
    • Sub-Investigator: Olha Kostenko
    • Principal Investigator: Oleksandra Steshenko
  • Rivne, Ukraine, 33000
    • Recruiting
    • Municipal Institution "Regional Perinatal Center" of Rivne Regional Council
    • Contact: Marharyta Tsilinska
    • Principal Investigator: Marharyta Tsilinska
    • Sub-Investigator: Oleh Melnychuk
  • Sumy, Ukraine, 40000
    • Not yet recruiting
    • Municipal non-profit enterprise Sumy regional council "Regional Clinical Perinatal Center"
    • Contact: Maryna Kuzomenska, Professor
    • Principal Investigator: Maryna Kuzomenska, Professor
    • Sub-Investigator: Valentyna Kalashnyk
    • Sub-Investigator: Tetiana Briazkalo
  • Zaporizhzhia, Ukraine, 69071
    • Not yet recruiting
    • Municipal non-profit enterprise "Maternity hospital №3" of Zaporizhia City Council
    • Contact: Natalia Lutsenko, Professor
    • Principal Investigator: Natalia Lutsenko, Professor
    • Sub-Investigator: Inna Yevterieva, Ph.D.
  • Cherkasy Region
    • Cherkasy, Cherkasy Region, Ukraine, 18000
      • Not yet recruiting
      • Municipal non-profit enterprise "Cherkasy Regional Hospital of Cherkasy Regional Council"
      • Contact: Vladyslav Pochynok
      • Principal Investigator: Vladyslav Pochynok
      • Sub-Investigator: Nataliia Lakusta, Ph.D
      • Sub-Investigator: Nataliia Oleksyna

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Rh-negative women who are not sensitized to Rh0 (D) antigen between the ages of 18 and 45;
• signed informed patient consent to participate in the study;
• pregnancy from a Rh-positive man;
• immunocompetent patients (CD 4+ counts above 200 per μl, HIV negative, or those with the virus particle count of less than 200 per μl or 400000 per ml);
• body mass index should be within normal limits (> 18.5 kg / m2 and <30.0 kg / m2);
• patients who have not received blood transfusions and / or medicinal products containing immunoglobulins in the last 6 months, in particular antibodies to Rh0 (D) antigen;
• persons who do not have acute and chronic cardiovascular, neuroendocrine, kidney, liver diseases, diseases of gastrointestinal tract, respiratory system;
• the results of physical, instrumental and laboratory examination of patients should be within the norma or deviations should be regarded by the researcher as clinically insignificant;
• the ability, according to the researcher, to comply with all the requirements of the study protocol.

Exclusion Criteria:

• sensitization to Rh0 (D) antigen;
• the absence of reliable anamnestic data on the prevention of Rh incompatibility in previous pregnancy (s) with the birth of a Rh-positive child;
• selective IgA deficiency in the presence of antibodies against immunoglobulin A (IgA);
• history of severe allergic reactions to the administration of human blood protein preparations;
• hypersensitivity reactions to human donor immunoglobulins;
• severe thrombocytopenia and other hemostatic disorders;
• life-threatening conditions and / or complications that require intensive care / surgery, the presence of any other bleeding at the time of screening;
• Rh-negative fetus;
• any other concomitant decompensated diseases or acute conditions, the presence of which, according to the researcher, can significantly affect the study results;
• participation in any other clinical trial in the last 3 months and throughout the study.

Additional exclusion criteria:

Subgroup "Pharmacokinetics" (patients included in the additional study of some pharmacokinetic parameters):

• any previous disease or intervention that, according to the researcher, may affect the pharmacokinetics of the study drug, in particular, organ and bone marrow transplantation, cancers;
• presence of HIV, hepatitis B, or C viruses;
• presence of severe clinical and laboratory manifestations of impaired liver and kidney function

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: Main group; Patients receive two prophylactic doses of the Human Anti-D (rh) immunoglobulin at a dose of 300 mcg - at 28 weeks of gestation and within 72 hours after delivery. Patients receive the second dose only in the case of the birth of an Rh-positive child. Before and after each injection of the drug, blood will be taken to control the level of anti-Rh0 (D) antibodies. after the last injection of the drug, blood samples are taken after 3 and 6 months to assess sensitization to the Rh antigen. 15 participants from the Main group are formed the "Pharmacokinetics" subgroup for additional blood samples taking, to determine the pharmacokinetic parameters

Drug: Human Anti-D (rh) immunoglobulin; prevention of Rh-sensitization in pregnant women in the antenatal and postnatal period in routine clinical practice. The study drug is administered twice at a dose of 300 mcg - at 28 weeks of gestation and within 72 hours after delivery.; Other Names: Rhesoglobin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The part of patients with no antibodies to Rh0 (D) antigen	The proportion of patients with no antibodies to Rh0 (D) antigen 6 months after the last administration of the drug	6 months after the last administration of the drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer of anti-Rh0 (D) antibodies	Titer of anti-Rh0 (D) antibodies 3 months after delivery	3 months after delivery
Titer of anti-Rh0 (D) antibodies	Titer of anti-Rh0 (D) antibodies 6 months after delivery	6 months after delivery
The part of patients with no antibodies to Rh0 (D) antigen 3 months after delivery	Proportion of patients with no antibodies to Rh0 (D) antigen 3 months after the last administration of the drug	3 months after the last administration of the drug
Proportion of patients who developed adverse events and reactions (AE / AR)	Proportion of patients who developed adverse events and reactions (AE / AR) associated with the administration of the drug, stratified by severity	9 months from the first administration of the drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum clearance	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
volume of distribution	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Area under the curve (AUC)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Half-life time (T1/2 α and β)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Maximum/peak serum concentration (Cmax)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Time to reach the maximum serum concentration (Tmax)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Elimination rate constant (Kel)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug

Collaborators and Investigators

• Sponsor: Biopharma Plasma LLC
• Collaborators: Ivano-Frankivsk National Medical University; State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine

Publications and helpful links

Helpful Links

• European Medicines Agency Guideline for Clinical investigation of human anti-D immunoglobulin for intravenous and/or intramuscular use, CPMP/BPWG/575/99 Rev. 1

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: January 6, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Rh-immunization prevention; human anti-D (rh) immunoglobulin; Rh-negative women; prenatal prophylaxis; postnatal prophylaxis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 1901-RH-BF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The results will be published after trial completion. Access to parts of Clinical Study Report (CSR) planned after the release of scientific publications.

Individual participant data (IPD) with the code of each patient will be available In CSR

• IPD Sharing Time Frame: After the scientific publication of trial results, 3 months later
• IPD Sharing Access Criteria: For specialists in field medicine, pharmacy, scientists
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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