Kinetics of Blood Platelets Transfused to Healthy Subjects

Summary

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.

Conditions

• Fetal and Neonatal Alloimmune Thrombocytopenia

Interventions

OTHER

Platelet transfusion

Transfusion of a platelet dose from 20 × 10ˆ9 to 100 × 10ˆ9.

Sponsors & Collaborators

• Larix A/S

  collaborator INDUSTRY

• Fraunhofer Institute for Translational Medicine and Pharmacology ITMP

  collaborator OTHER

• Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen

  collaborator OTHER

• Bioscientia Central Laboratory

  collaborator UNKNOWN

• Prophylix Pharma AS

  lead INDUSTRY

Principal Investigators

• Jens Kjeldsen-Kragh, MD, PhD · Prophylix Pharma AS

• Michaela Köhm, MD · Fraunhofer Institute for Molecular Biology and Applied Ecology IME

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-04-17

Primary Completion

2018-12-10

Completion

2018-12-10

Countries

• Germany

Study Locations