Kinetics of Blood Platelets Transfused to Healthy Subjects

Brief Title

Kinetics of Blood Platelets Transfused to Healthy Subjects

Official Title

An Open-label, Single Centre, Exploratory Trial Investigating the Kinetics of Platelets Transfused to Healthy, Male Subjects

Brief 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.
    

Study Type

Interventional

Primary Outcome

Terminal elimination half live

Secondary Outcome

 Cmax

Condition

Fetal and Neonatal Alloimmune Thrombocytopenia

Intervention

Platelet transfusion

Study Arms / Comparison Groups

 Platelet transfusion

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Other

Estimated Enrollment

25

Start Date

April 17, 2018

Completion Date

December 10, 2018

Primary Completion Date

December 10, 2018

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent must be obtained before any trial related procedures are
             performed

          2. Healthy, male subjects

          3. Age ≥18 and < 50 years old

          4. BMI < 30kg/mˆ2

          5. HLA-A2 and/or HLA-A9 negative

        Exclusion Criteria:

          1. History of hypersensitivity to platelet concentrates or human plasma protein

          2. Subjects with known IgA deficiency and anti-IgA antibodies

          3. Blood donation received within 3 weeks

          4. Platelet counts < 150 × 10ˆ9/L or > 450 × 10ˆ9/L

          5. Any type of known platelet function disorder

          6. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs, e.g. acetylsalicylic
             acid) or selective serotonin reuptake inhibitors within 7 days prior to Visit 1

          7. Chronic or ongoing active infectious disease requiring systemic treatment including,
             but not limited to, chronic and renal infection, chronic chest infection with
             bronchiectasis, and tuberculosis

          8. Participation in any other interventional clinical trial during the trial period

          9. Subjects known or suspected of not being able to comply with this trial protocol (e.g.
             due to alcoholism, drug dependency or psychological disorder)

         10. Presence of HLA-antibodies class I (MFI level > 3000)

         11. Signs of previous or ongoing infection with HIV and/or Hepatitis B and/or C virus
      

Gender

Male

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Jens Kjeldsen-Kragh, MD, PhD, , 

Location Countries

Germany

Location Countries

Germany

NCT ID

NCT03561909

Organization ID

PX-0

Responsible Party

Sponsor

Study Sponsor

Prophylix Pharma AS

Collaborators

 Larix A/S

Study Sponsor

Jens Kjeldsen-Kragh, MD, PhD, Study Chair, Prophylix Pharma AS

Verification Date

May 2019