Biotin-RBC Transfusion in SCD

Kinetics of Red Blood Cell Clearance in Chronically Transfused Children With Sickle Cell Disease

This is a single-arm, mechanistic clinical trial to measure predictors of senescence and the in vivo survival of transfused red blood cells (RBCs) in individuals with sickle cell disease (SCD) receiving chronic transfusion therapy (CTT). Chronic transfusion in patients with SCD is a common treatment. The efficacy of RBC transfusion therapy to treat or prevent complications of SCD may be hampered by variable survival of the transfused donor RBC. The overall aim is to see how long RBC survive in SCD patients who are chronically transfused. When a study participant has a regular blood transfusion the researchers will label a small portion of the RBCs that are transfused with biotin. The participant will return at Day 1, weekly for 3 months and monthly for 3 months to measure how long those RBCs survive. An optional sub-study using INTERCEPT RBCs will mirror the main study but will use INTERCEPT RBCs that have biotinylated for 1 RBC unit.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Biotin Labeled Red Blood Cells; Device: Pathogen-reduced Biotin Labeled Red Blood Cells

Detailed Description

Sickle cell disease (SCD) carries significant morbidity as a result of red blood cell (RBC) sickling and hemolysis. Stroke is one of the most devastating sequelae of SCD. Chronic transfusion therapy (CTT) reduces stroke risk by supplying normal, non-sickle RBC to circulation, thereby reducing the percentage of endogenous sickle RBC in circulation, and maintaining a higher hemoglobin (Hb), thereby suppressing erythropoiesis of new sickle RBC. While the efficacy of CTT in stroke prophylaxis is well-established, nearly 45% of children continue to have silent or overt strokes despite CTT. The failure of CTT to prevent stroke events may be related to inadequate reduction of circulating sickle RBC and erythropoiesis. The amount of circulating sickle-RBC is related to the survival kinetics of both transfused RBC and endogenous sickle RBC.

In a large, longitudinal analysis of CTT in SCD, the researchers found wide variation in the survival of donor RBC following transfusion, with faster clearance associated with patient immune features (historical RBC alloimmunization and spleen presence) and with donor RBC glucose-6-phosphate-dehydrogenase (G6PD) deficiency. To better understand the roles of patient and donor factors in the survival and clearance of transfused RBC, the researchers propose a mechanistic, clinical trial during chronic transfusion episodes in patients with SCD, in which a small aliquot of each transfused unit is labeled with biotin conjugated to RBC surface proteins, to safely identify and measure the in vivo survival of donor RBC.

Aim 1 will examine the relationships of the recipient's immune system (past alloimmunization, splenic volume, and markers of reticuloendothelial system function) on the post-transfusion survival of biotin-labeled donor RBC.

Aim 2 will examine the relationships of donor RBC G6PD levels and donor RBC metabolomics with the in vivo survival and changes in donor RBC senescence markers.

Aim 3 will compare the in vivo survival and clearance rate of phenotype-matched RBCs prepared with an investigational pathogen-reduction system (INTERCEPT Blood System) vs. the in vivo survival and clearance rate of conventional, phenotype-matched RBCs (not treated with INTERCEPT). Biotin labeling of donor RBC will be used to measure RBC survival. This is an optional study activity for study participants.

Completion of these aims will increase the understanding of mechanisms for the variability in RBC survival during CTT, identifying donor and recipient risk factors for decreased RBC survival. Ultimately this knowledge will inform the management of CTT to improve the prevention of strokes in SCD.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Hughes Spalding Children's Hospital
    • Atlanta, Georgia, United States, 30322
      • Childrens Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30322
      • Grady Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hemoglobinopathy:

  • Any sickle cell disease genotype, or
  • Transfusion-dependent thalassemia (TDT)
• Receiving CTT for ≥3 months prior to enrollment
• For participants with past BioRBC transfusion exposure, BioRBC antibody screens must have been conducted through at least 6 months post exposure, with negative results

Exclusion Criteria:

• Anticipated cessation of CTT in the next ≤2 months
• Ongoing consumption of biotin or raw egg dietary supplements
• Antibody specific of INTERCEPT RBCs at baseline (for subjects consenting to the optional arm)
• BioRBC-specific antibodies ever detected in the past, or detected on post-enrollment screening prior to first infusion of Bio-RBC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biotin Labeled Red Blood Cells; Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs). Participants receive 2 or 3 units of transfused blood, depending on clinical care, and a portion of all units are biotin-labeled. Samples are taken for 12 weeks after the biotinylated transfusion. Participants continue to receive regular monthly transfusions (non-biotinylated) as part of their usual chronic transfusion therapy (CTT) during the follow-up period for this study.

Drug: Biotin Labeled Red Blood Cells; On the day of transfusion, a 20 mL aliquot is sterilely withdrawn from each RBC unit, washed and labeled with sulfo-NHS-biotin for 30 minutes, washed to stop the labeling reaction, then resuspended in plasma to a hematocrit of ~60%. The biotin-labeled RBC (BioRBC) is transfused along with the remainder of the RBC unit (unlabeled volume). Standard blood bank and CTT protocols and minor antigen matching for SCD patients are followed. Exact transfusion volume is determined based on pre-transfusion hemoglobin (Hb), sickle cell hemoglobin (HbS), and body weight, per clinical protocol.; Device: Pathogen-reduced Biotin Labeled Red Blood Cells; Participants taking part in this optional intervention have one transfusion episode with blood using the INTERCEPT Blood System. For this transfusion, a portion of each blood unit is biotin-labeled and one of those units has the INTERCEPT treatment. In addition to the blood drawn for the main study, individuals participating in this optional intervention have additional tubes of peripheral venous blood drawn for evaluating treatment-emergent antibodies specific to INTERCEPT RBCs and acridine surface label monitoring. Tests for treatment-emergent antibodies specific to INTERCEPT RBCs are performed according to procedures developed by Cerus Corporation. This optional study activity examines the survival of transfused RBCs with and without the INTERCEPT treatment.; Other Names: INTERCEPT Blood System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Potential Lifespan (MPL) of Biotinylated RBCs	The long-term lifespan of transfused biotin labeled RBCs is assessed as the linearly extrapolated as mean potential lifespan (MPL) of biotinylated RBCs.	Up to Day 70
Percentage of Biotin Labeled RBCs	Survival of the transfused biotin-labeled RBCs (B-RBCs) at each time point was expressed as a ratio (percentage) compared to the initial 15-minute-post-transfusion B-RBC concentration. From measurements obtained from 24-hours through week 12 post-transfusion, survival was plotted over time, and recovery measurements were extrapolated.	Posttransfusion 24-hour recovery (PTR-24), 28-day recovery, and 90-day recovery
Half-life of Biotinylated RBCs	Survival of transfused biotin labeled RBCs is assessed as the half-life of biotinylated RBCs. Half-life is defined only for BioRBC that remain in circulation for at least one day post transfusion.	Day 1 (24 hours post-transfusion) up to Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Biotin Labeled RBCs Among Participants Receiving Pathogen-Reduced RBC Unit	Survival of the transfused biotin-labeled RBCs (B-RBCs) at each time point was expressed as a ratio (percentage) compared to the initial 15-minute-post-transfusion B-RBC concentration. To compare the survival of transfused RBCs with and without the pathogen-reduced (PR) treatment, two different RBC units to transfuse were divided into 3 different labeled aliquots: RBC before PR, RBC after PR, and conventional RBC. The participants received the 3 biotin-labeled RBC aliquots and the survival of the 3 aliquots was examined over time with repeated blood samples.	Posttransfusion 24-hour recovery (PTR-24)
Half-life of Biotinylated RBCs Among Participants Receiving Pathogen-Reduced RBC Unit	Survival of transfused biotin labeled RBCs is assessed as the half-life of biotinylated RBCs. Half-life is defined only for BioRBC that remain in circulation for at least one day post transfusion. To compare the survival of transfused RBCs with and without the pathogen-reduced (PR) treatment, two different RBC units to transfuse were divided into 3 different labeled aliquots: RBC before PR, RBC after PR, and conventional RBC. The participants received the 3 biotin-labeled RBC aliquots and the survival of the 3 aliquots was examined over time with repeated blood samples.	Day 1 (24 hours post-transfusion) up to Week 12
Estimated Time to RBC Clearance Among Participants Receiving Pathogen-Reduced RBC Unit	The estimated time to RBC clearance is extrapolated by a slope from samples obtained from Day 28 to Day 112 survival data. To compare the survival of transfused RBCs with and without the pathogen-reduced (PR) treatment, two different RBC units to transfuse were divided into 3 different labeled aliquots: RBC before PR, RBC after PR, and conventional RBC. The participants received the 3 biotin-labeled RBC aliquots and the survival of the 3 aliquots was examined over time with repeated blood samples.	Day 28 to Day 112

Collaborators and Investigators

• Sponsor: Marianne Yee
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Cerus Corporation
• Investigators: Principal Investigator: Marianne Yee, MD, Emory University

Publications and helpful links

General Publications

• Yee MEM, Zerra PE, Francis RO, Easley KA, Lough CM, McCoy JW 3rd, Naseh Z, Delvadia BB, Parikh AK, Butler HE, Stowell SR, Joiner CH, Josephson CD, Roback JD, Fasano RM. Red cell transfusion survival in sickle cell disease is reduced by donor characteristics and recipient spleen activity. Blood Adv. 2026 Apr 22:bloodadvances.2025019005. doi: 10.1182/bloodadvances.2025019005. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2021
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Chronic transfusion therapy
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Physiological Effects of Drugs; Micronutrients; Vitamin B Complex; Vitamins; Biotin
• Other Study ID Numbers: IRB00117580; 1K23HL146904 (U.S. NIH Grant/Contract); 2024P008374 (Other Identifier: Emory Insight Humans IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial will be made available for sharing with other researchers, after deidentification.
• IPD Sharing Time Frame: Individual participant data will be made available for sharing immediately following publication, with no end date.
• IPD Sharing Access Criteria: Data will be available for sharing with researchers who provide a methodologically sound proposal, for the purpose of achieving the aims in the approved proposal. Proposals should be directed to Marianne.Yee@choa.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No