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

Pregnancy Related Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05245734
• Other study ID #: 1901-RH-BF
• Status: Recruiting
• Phase: Phase 4
• Start date: February 8, 2022
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Biopharma Plasma LLC
• Contact: Yaroslav Zhebelenko, Ph.D., MD
• Phone: +380977495979
• Email: y.zhebelenko[@]biopharma.ua
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 281
• Est. completion date: April 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Pregnancy Related

Intervention

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.

Locations

Country	Name	City	State
Ukraine	Municipal non-profit enterprise "Cherkasy Regional Hospital of Cherkasy Regional Council"	Cherkasy	Cherkasy Region
Ukraine	Municipal non-profit enterprise "Maternity hospital" of the Chernihiv city council	Chernihiv
Ukraine	Municipal non-profit enterprise "Chernivtsi Regional Perinatal Center"	Chernivtsi
Ukraine	Municipal enterprise "Dnipropetrovsk Regional Perinatal Center (DRPC) with a hospital" of the Dnipropetrovsk Regional Council	Dnipro
Ukraine	Municipal non-profit enterprise "Ivano-Frankivsk Regional Perinatal Center Ivano-Frankivsk Regional Council"	Ivano-Frankivsk
Ukraine	Municipal non-profit enterprise "Khmelnytsky Regional Hospital" of the Khmelnytsky Regional Council	Khmelnytskyi
Ukraine	Municipal non-profit enterprise "Kirovohrad Regional Hospital of the Kirovohrad Regional Council"	Kropyvnytskyi
Ukraine	Kyiv City Center for Reproductive and Perinatal Medicine	Kyiv
Ukraine	State Institution "Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova National Academy of Medical Sciences of Ukraine "	Kyiv
Ukraine	Municipal enterprise "Volyn Regional Territorial Medical Association for the Protection of Motherhood and Childhood" Volyn Regional Council	Luts'k
Ukraine	Municipal non-profit enterprise Lviv Regional Council "Lviv Regional Clinical Perinatal Center"	Lviv
Ukraine	Municipal non-profit enterprise "Mykolayiv regional clinical hospital" of the Mykolayiv regional council	Mykolayiv
Ukraine	Municipal enterprise "Poltava Regional Clinical Hospital named after M.V. Sklifosovsky Poltava regional council"	Poltava
Ukraine	Municipal Institution "Regional Perinatal Center" of Rivne Regional Council	Rivne
Ukraine	Municipal non-profit enterprise Sumy regional council "Regional Clinical Perinatal Center"	Sumy
Ukraine	Municipal non-profit enterprise "Maternity hospital ?3" of Zaporizhia City Council	Zaporizhzhia

Sponsors (3)

Lead Sponsor	Collaborator
Biopharma Plasma LLC	Ivano-Frankivsk National Medical University, State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine

Country where clinical trial is conducted

Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum clearance	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Other	volume of distribution	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Other	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
Other	Half-life time (T1/2 a and ß)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Other	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
Other	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
Other	Elimination rate constant (Kel)	Pharmacokinetic parameter are determined after first administration of the study drug	3 months after first administration of the study drug
Primary	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	Titer of anti-Rh0 (D) antibodies	Titer of anti-Rh0 (D) antibodies 3 months after delivery	3 months after delivery
Secondary	Titer of anti-Rh0 (D) antibodies	Titer of anti-Rh0 (D) antibodies 6 months after delivery	6 months after delivery
Secondary	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
Secondary	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

External 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