RHD Genotype Matched Red Cells for Anti-D

Early Phase 1

Completed

• Conditions: Sickle Cell Disease; Anti-D Antibodies
• Interventions: Biological: D+ RH genotype matched red cell units for transfusion

• Registration Number: NCT04156906
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically transfused patients with sickle cell disease (SCD) who type D+ but have formed anti-D and are currently transfused with D- RBC (Red Blood Cell) units.

Detailed Description

Red blood cell transfusion remains a critical therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in patients with SCD. Recent studies performed by Investigators and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Anti-D formation in D+ patients occurs frequently, and once identified, providing D- cells for all subsequent transfusions can be challenging. These anti-D antibodies in D+ patients suggest exposure to different or variant D protein on donor cells. Investigators will test whether transfusion of patients with anti-D with RHD genotyped matched red cells is feasible, safe and can decrease D- donor unit demand.

Study Timeline

• Study First Submitted: 2019-11-06
• Study First Submitted QC: 2019-11-06
• Study First Posted: 2019-11-08
• Study Start: 2020-07-08
• Primary Completion: 2024-03-04
• Study Completion: 2024-10-04
• Results First Submitted: 2025-04-09
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-01
• Last Update Submitted: 2025-05-01
• Results First Posted: 2025-05-02
• Last Update Posted: 2025-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Subjects age > 8 years old
• Diagnosis of SCD, all genotypes
• Require chronic red cell transfusion therapy
• History of anti-D
• RH genotype predicts D+ expression

Exclusion Criteria

• Rare RH genotype that would preclude sufficient RBC units
• Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
D+ RH genotype matched Red Blood Cell Transfusion	D+ RH genotype matched red cell units for transfusion	Investigators will provide one red cell unit of D+ RH genotype matched RBCs at the first transfusion study visit. The remainder of units will be provided per clinical standard of care, i.e. D-, CEK-matched, and negative for all other antigens the patient is alloimmunized against. If laboratory monitoring shows no reappearance of anti-D and no signs of increased red cell hemolysis, the patient will receive one unit of D+ RH genotype matched RBCs at the 2nd transfusion study visit, and if tolerated, D+ red cell exposures will increase by one unit per study visit until all units required are D+.

Primary Outcome Measures

Name	Time	Method
Anti-D Recurrence	Through study completion and follow-up phase, an average of 10 months per participant	To determine safety of providing RH genotype match red cells to patients with a history of anti-D, we observed if anti-D reappearance occurred or evidence of hemolysis of transfused red cells.

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States