Sickle Cell DiseasePhase 1NCT04426591
Biotin-RBC Transfusion in SCD
A Phase 1 study testing Biotin Labeled Red Blood Cells and Pathogen-reduced Biotin Labeled Red Blood Cells in people with Sickle Cell Disease, run by Marianne Yee at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Biotin Labeled Red Blood Cells and Pathogen-reduced Biotin Labeled Red Blood Cells
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Oct 2021to 30 Apr 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Hughes Spalding Children's Hospital
Atlanta, Georgia, 30303
Childrens Healthcare of Atlanta
Atlanta, Georgia, 30322
Grady Health System
Atlanta, Georgia, 30322
About this study
Official title: 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.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Biotin Labeled Red Blood Cells, Pathogen-reduced Biotin Labeled Red Blood Cells
- Keywords
- Chronic transfusion therapy
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biotin Labeled Red Blood CellsDrug
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.
Pathogen-reduced Biotin Labeled Red Blood CellsDevice
Also called INTERCEPT Blood System
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Biotin Labeled Red Blood Cells; Device: Pathogen-reduced Biotin Labeled Red Blood Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start29 Oct 2021
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marianne Yee
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Cerus Corporation
- Responsible party
- Sponsor-investigator, Marianne Yee, Emory University
- Investigators
- Marianne Yee, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04426591
- Sponsor's protocol ID
- IRB00117580
- Other IDs
- 1K23HL146904, 2024P008374
- Status last verified
- Apr 2026
- First submitted
- 29 May 2020
- Last updated
- 22 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All of the individual participant data collected during the trial will be made available for sharing with other researchers, after deidentification.
Publications
Yee MEM, Zerra PE, Francis RO, Easley KA, Lough CM, McCoy JW, Naseh Z, Delvadia BB, Parikh AK, Butler HE, Stowell SR, Joiner CH, Josephson CD, Roback JD, Fasano RM. Red blood cell transfusion survival in sickle cell disease is reduced by donor characteristics and recipient spleen activity. Blood Adv. 2026 Jul 14;10(13):4439-4449. doi: 10.1182/bloodadvances.2025019005.
PubMed 42018645
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Kinetics of Red Blood Cell Clearance in Chronically Transfused Children With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04426591
- Acronym / sponsor ID
- IRB00117580
- Conditions
- Sickle Cell Disease
- Keywords
- Chronic transfusion therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Marianne YeeUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Cerus Corporation
- Study start
- 29 Oct 2021 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 22 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Biotin Labeled Red Blood Cells | Experimental | Drug: Biotin Labeled Red Blood Cells, Device: Pathogen-reduced Biotin Labeled Red Blood CellsParticipants 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. |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Hemoglobinopathy:
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biotin Labeled Red Blood CellsOn 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. | Drug | Biotin Labeled Red Blood Cells |
| Pathogen-reduced Biotin Labeled Red Blood CellsAlso: INTERCEPT Blood SystemParticipants 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. | Device | Biotin Labeled Red Blood Cells |
Primary outcome
Percentage of Biotin Labeled RBCs
Time frame: Posttransfusion 24-hour recovery (PTR-24), 28-day recovery, and 90-day recovery
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.
Half-life of Biotinylated RBCs
Time frame: Day 1 (24 hours post-transfusion) up to Week 12
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.
Mean Potential Lifespan (MPL) of Biotinylated RBCs
Time frame: Up to Day 70
The long-term lifespan of transfused biotin labeled RBCs is assessed as the linearly extrapolated as mean potential lifespan (MPL) of biotinylated RBCs.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42018645Yee MEM, Zerra PE, Francis RO, Easley KA, Lough CM, McCoy JW, Naseh Z, Delvadia BB, Parikh AK, Butler HE, Stowell SR, Joiner CH, Josephson CD, Roback JD, Fasano RM. Red blood cell transfusion survival in sickle cell disease is reduced by donor characteristics and recipient spleen activity. Blood Adv. 2026 Jul 14;10(13):4439-4449. doi: 10.1182/bloodadvances.2025019005.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial will be made available for sharing with other researchers, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marianne Yee, MD principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biotin Labeled Red Blood Cells and Pathogen-reduced Biotin Labeled Red Blood Cells in people with Sickle Cell Disease, run by Marianne Yee at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Biotin Labeled RBCs (time frame: Posttransfusion 24-hour recovery (PTR-24), 28-day recovery, and 90-day recovery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04426591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.