Kinetics of Blood Platelets Transfused to Healthy Subjects
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|ClinicalTrials.gov Identifier: NCT03561909|
Recruitment Status : Completed
First Posted : June 19, 2018
Last Update Posted : May 10, 2019
The current phase 0 trial is preceding the phase 1/2 trial of a newly developed drug, NAITgam, for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) - a rare, but potentially very severe bleeding condition in the fetus or newborn. FNAIT may occur in women whose blood platelets do not express HPA-1a. If the fetus has inherited HPA-1a from the father, the mother's immune system may be stimulated to produce HPA-1a antibodies if HPA-1a positive fetal blood platelets enter the maternal circulation during delivery. In a subsequent pregnancy, such antibodies will cross the placenta and may reduce the number of HPA-1a positive blood platelets in the fetus, which in turn may result in severe bleeding in the fetus or newborn.
The phase 1/2 study of NAITgam will examine NAITgam's ability to eliminate HPA-1a positive blood platelets that has been transfused to healthy male subjects, whose blood platelet do not express HPA-1a. The ability to quickly eliminate transfused HPA-1a positive platelets is considered as a surrogate endpoint for NAITgam's ability to prevent formation of antibodies against HPA-1a after delivery of an HPA-1a positive child.
The current phase 0 trial will examine the survival of blood platelets transfused to healthy male individuals without subsequent administration of NAITgam. The natural survival of transfused platelet, as determined in the phase 0 trial, will be compared with the survival of transfused HPA-1a positive platelets after administration of NAITgam in the phase 1/2 trial. The aim of the phase 0 trial is first, to determine the dose of blood platelet that should be transfused to the healthy subjects in the phase 1/2 trial; and secondly, to determine the optimal time point, after transfusion of platelets, for administration of NAITgam in the phase 1/2 trial.
Eight to 24 healthy male subjects will be included in the phase 0 trial. After transfusion of platelets, blood samples will be collected at regular intervals to determine the proportion of transfused blood platelets. Differences between tissue type antigens between donor and recipient will be used to determine the proportion of transfused platelets. Survival of transfused platelets will be performed by flow cytometry - a method that can be used to quantify very small proportions of cells in the blood. Fluorochrome-conjugated monoclonal antibodies against HLA-A2 and HLA-A9 will be used for flow cytometric identification the transfused platelets.
|Condition or disease||Intervention/treatment||Phase|
|Fetal and Neonatal Alloimmune Thrombocytopenia||Other: Platelet transfusion||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Single Centre, Exploratory Trial Investigating the Kinetics of Platelets Transfused to Healthy, Male Subjects|
|Actual Study Start Date :||April 17, 2018|
|Actual Primary Completion Date :||December 10, 2018|
|Actual Study Completion Date :||December 10, 2018|
HLA-A2 and/or HLA A9 negative healthy study subjects will be transfused with a small dose of platelets from an HLA-A2 and/or HLA-A9 positive donor.
Other: Platelet transfusion
Transfusion of a platelet dose from 20 × 10ˆ9 to 100 × 10ˆ9.
- Terminal elimination half live [ Time Frame: The terminal elimination half live of transfused platelets will be determined based on the survival of platelets within the first 5 days after trandfusion ]Determination of the terminal elimination half live of a single platelet dose transfused to healthy male subjects
- Cmax [ Time Frame: Will be determined within the first 5 days after transfusion ]The peak platelet concentration
- AUC [ Time Frame: Will be determined within the first 5 days after transfusion ]The area under the platelet concentration versus time curve
- Clearance [ Time Frame: Will be determined within the first 5 days after transfusion ]Natural clearance of platelets from the circulation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03561909
|Fraunhofer Institute for Molecular Biology and Applied Ecology IME|
|Frankfurt am main, Hessia, Germany, 60596|
|Study Chair:||Jens Kjeldsen-Kragh, MD, PhD||Prophylix Pharma AS|
|Principal Investigator:||Michaela Köhm, MD||Fraunhofer Institute for Molecular Biology and Applied Ecology IME|