Biotin-RBC Transfusion in SCD

NCT04426591 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 3 other identifiers: IRB001175801K23HL1469042024P008374
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Sickle Cell Disease

Keywords

Chronic transfusion therapy

Outcome Measures

Primary Outcomes (3)

• 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

• 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

Other Outcomes (3)

• Percentage of Biotin Labeled RBCs Among Participants Receiving Pathogen-Reduced RBC Unit

  Posttransfusion 24-hour recovery (PTR-24)

• Half-life of Biotinylated RBCs Among Participants Receiving Pathogen-Reduced RBC Unit

  Day 1 (24 hours post-transfusion) up to Week 12

• Estimated Time to RBC Clearance Among Participants Receiving Pathogen-Reduced RBC Unit

  Day 28 to Day 112

Study Arms (1)

Biotin Labeled Red Blood Cells

EXPERIMENTAL

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; Device: Pathogen-reduced Biotin Labeled Red Blood Cells

Interventions

Biotin Labeled Red Blood Cells DRUG

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.

Biotin Labeled Red Blood Cells

Pathogen-reduced Biotin Labeled Red Blood Cells DEVICE

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.

Also known as: INTERCEPT Blood System

Biotin Labeled Red Blood Cells

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Marianne Yee: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Cerus Corporation: collaborator

Study Sites (3)

Hughes Spalding Children's Hospital

Atlanta, Georgia, 30303, United States

Location

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Grady Health System

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 42018645 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Marianne Yee, MD, MSc
• Organization: Emory University

memcphe@emory.edu

404-785-6190

Study Officials

• Marianne Yee, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 11, 2020
• Study Start: October 29, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: May 22, 2026
• Results First Posted: May 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Individual participant data will be made available for sharing immediately following publication, with no end date.
• 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.

Locations

US (3)