Clinical trial NCT05245734: Human Anti-D (rh) Immunoglobulin (Rhesoglobin) Efficacy, Safety and Some Pharmacokinetics Parameters in Pregnant Women
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pregnancy Related
Keywords: Rh-immunization prevention
human anti-D (rh) immunoglobulin
Rh-negative women
prenatal prophylaxis
postnatal prophylaxis
Lead sponsor: Biopharma Plasma LLC
Sponsor class: INDUSTRY
Collaborators: name: State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine
name: Ivano-Frankivsk National Medical University
First posted: 2022-02-18
Enrollment: 281
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: uncontrolled, open-label, multicenter, international (From the total number of patients a subgroup for studying some pharmacokinetics parameters is formed )
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The part of patients with no antibodies to Rh0 (D) antigen
timeFrame: 6 months after the last administration of the drug
Secondary outcomes:
measure: Titer of anti-Rh0 (D) antibodies
timeFrame: 3 months after delivery
measure: Titer of anti-Rh0 (D) antibodies
timeFrame: 6 months after delivery
measure: The part of patients with no antibodies to Rh0 (D) antigen 3 months after delivery
timeFrame: 3 months after the last administration of the drug
measure: Proportion of patients who developed adverse events and reactions (AE / AR)
timeFrame: 9 months from the first administration of the drug
Other outcomes:
measure: Serum clearance
timeFrame: 3 months after first administration of the study drug
measure: volume of distribution
timeFrame: 3 months after first administration of the study drug
measure: Area under the curve (AUC)
timeFrame: 3 months after first administration of the study drug
measure: Half-life time (T1/2 α and β)
timeFrame: 3 months after first administration of the study drug
measure: Maximum/peak serum concentration (Cmax)
timeFrame: 3 months after first administration of the study drug
measure: Time to reach the maximum serum concentration (Tmax)
timeFrame: 3 months after first administration of the study drug
measure: Elimination rate constant (Kel)
timeFrame: 3 months after first administration of the study drug
Locations:
city: Cherkasy
country: Ukraine
facility: Municipal non-profit enterprise "Cherkasy Regional Hospital of Cherkasy Regional Council"
state: Cherkasy Region
city: Chernihiv
country: Ukraine
facility: Municipal non-profit enterprise "Maternity hospital" of the Chernihiv city council
city: Chernivtsi
country: Ukraine
facility: Municipal non-profit enterprise "Chernivtsi Regional Perinatal Center"
city: Dnipro
country: Ukraine
facility: Municipal enterprise "Dnipropetrovsk Regional Perinatal Center (DRPC) with a hospital" of the Dnipropetrovsk Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Municipal non-profit enterprise "Ivano-Frankivsk Regional Perinatal Center Ivano-Frankivsk Regional Council"
city: Khmelnytskyi
country: Ukraine
facility: Municipal non-profit enterprise "Khmelnytsky Regional Hospital" of the Khmelnytsky Regional Council
city: Kropyvnytskyi
country: Ukraine
facility: Municipal non-profit enterprise "Kirovohrad Regional Hospital of the Kirovohrad Regional Council"
city: Kyiv
country: Ukraine
facility: State Institution "Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova National Academy of Medical Sciences of Ukraine "
city: Kyiv
country: Ukraine
facility: Kyiv City Center for Reproductive and Perinatal Medicine
city: Luts'k
country: Ukraine
facility: Municipal enterprise "Volyn Regional Territorial Medical Association for the Protection of Motherhood and Childhood" Volyn Regional Council
city: Lviv
country: Ukraine
facility: Municipal non-profit enterprise Lviv Regional Council "Lviv Regional Clinical Perinatal Center"
city: Mykolayiv
country: Ukraine
facility: Municipal non-profit enterprise "Mykolayiv regional clinical hospital" of the Mykolayiv regional council
city: Poltava
country: Ukraine
facility: Municipal enterprise "Poltava Regional Clinical Hospital named after M.V. Sklifosovsky Poltava regional council"
city: Rivne
country: Ukraine
facility: Municipal Institution "Regional Perinatal Center" of Rivne Regional Council
city: Sumy
country: Ukraine
facility: Municipal non-profit enterprise Sumy regional council "Regional Clinical Perinatal Center"
city: Zaporizhzhia
country: Ukraine
facility: Municipal non-profit enterprise "Maternity hospital №3" of Zaporizhia City Council
Study officials:
References: