Trial Outcomes & Findings for Biotin-RBC Transfusion in SCD (NCT NCT04426591)
NCT ID: NCT04426591
Last Updated: 2026-05-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
Posttransfusion 24-hour recovery (PTR-24), 28-day recovery, and 90-day recovery
Results posted on
2026-05-22
Participant Flow
Participants were recruited from Children's Healthcare of Atlanta, Grady Health System, and Hughes Spaulding Children's Hospital in Atlanta, Georgia, USA. Participant enrollment began October 29, 2021, and all follow-up assessments were completed by April 30, 2025.
Participant milestones
| Measure |
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.
Biotin Labeled Red Blood Cells: On the day of transfusion, a 20 mL aliquot is sterilely withdrawn from each RBC unit, washed and labeled with sulfo-NHS-biotin for 30 minutes, washed to stop the labeling reaction, then resuspended in plasma to a hematocrit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). 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 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. This optional study activity examines the survival of transfused RBCs with and without the INTERCEPT treatment.
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|---|---|
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Overall Study
STARTED
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22
|
|
Overall Study
Completed extended follow-up up to 16 weeks
|
21
|
|
Overall Study
Participated in optional pathogen-reduced biotin labeled RBCs study activity
|
6
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Biotin-RBC Transfusion in SCD
Baseline characteristics by cohort
| Measure |
Biotin Labeled Red Blood Cells
n=22 Participants
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.
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|---|---|
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Age, Categorical
<=18 years
|
13 Participants
n=2 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=2 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=2 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=2 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Black or African American
|
22 Participants
n=2 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=2 Participants
|
|
Region of Enrollment
United States
|
22 Participants
n=2 Participants
|
|
Sickle Cell Genotype
Hemoglobin SS
|
21 Participants
n=2 Participants
|
|
Sickle Cell Genotype
Hemoglobin S-Beta-Zero-Thalassemia
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1 Participants
n=2 Participants
|
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Red Blood Cell Alloimmunization
|
6 Participants
n=2 Participants
|
PRIMARY outcome
Timeframe: Posttransfusion 24-hour recovery (PTR-24), 28-day recovery, and 90-day recoverySurvival 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.
Outcome measures
| Measure |
Biotin Labeled Red Blood Cells
n=22 Participants
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.
|
Red Blood Cell Unit After Pathogen-Reduced Treatment
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs), after the pathogen-reduced treatment via the INTERCEPT Blood System.
|
Conventional RBC Unit
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with a conventional RBC unit.
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|---|---|---|---|
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Percentage of Biotin Labeled RBCs
24-hour recovery (PTR-24)
|
97.3 percentage of biotin-labeled RBCs
Interval 94.2 to 105.4
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—
|
—
|
|
Percentage of Biotin Labeled RBCs
28-day recovery
|
80 percentage of biotin-labeled RBCs
Interval 70.0 to 88.0
|
—
|
—
|
|
Percentage of Biotin Labeled RBCs
90-day recovery
|
21 percentage of biotin-labeled RBCs
Interval 14.0 to 27.0
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—
|
—
|
PRIMARY outcome
Timeframe: Day 1 (24 hours post-transfusion) up to Week 12Survival 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.
Outcome measures
| Measure |
Biotin Labeled Red Blood Cells
n=22 Participants
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.
|
Red Blood Cell Unit After Pathogen-Reduced Treatment
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs), after the pathogen-reduced treatment via the INTERCEPT Blood System.
|
Conventional RBC Unit
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with a conventional RBC unit.
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|---|---|---|---|
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Half-life of Biotinylated RBCs
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60 days
Interval 44.0 to 64.0
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—
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—
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PRIMARY outcome
Timeframe: Up to Day 70Population: MPL could not be calculated because B-RBC survival was non-linear, and participants did not reach full clearance, even with measurements up to Week 16. Instead, survival outcomes such as PTR-24, Day 28 recovery, Day 90 recovery, and T50 were used, with Day 90 recovery serving as the closest analogue to MPL (outcome measure 1).
The long-term lifespan of transfused biotin labeled RBCs is assessed as the linearly extrapolated as mean potential lifespan (MPL) of biotinylated RBCs.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Posttransfusion 24-hour recovery (PTR-24)Population: This analysis includes the 6 individuals participating in the optional study using pathogen-reduced treatment.
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.
Outcome measures
| Measure |
Biotin Labeled Red Blood Cells
n=6 Participants
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.
|
Red Blood Cell Unit After Pathogen-Reduced Treatment
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs), after the pathogen-reduced treatment via the INTERCEPT Blood System.
|
Conventional RBC Unit
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with a conventional RBC unit.
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|---|---|---|---|
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Percentage of Biotin Labeled RBCs Among Participants Receiving Pathogen-Reduced RBC Unit
|
106.7 percentage of biotin-labeled RBCs
Standard Deviation 5.3
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111.1 percentage of biotin-labeled RBCs
Standard Deviation 6.7
|
103.1 percentage of biotin-labeled RBCs
Standard Deviation 7.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 (24 hours post-transfusion) up to Week 12Population: This analysis includes the 6 individuals participating in the optional study using pathogen-reduced treatment.
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.
Outcome measures
| Measure |
Biotin Labeled Red Blood Cells
n=6 Participants
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.
|
Red Blood Cell Unit After Pathogen-Reduced Treatment
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs), after the pathogen-reduced treatment via the INTERCEPT Blood System.
|
Conventional RBC Unit
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with a conventional RBC unit.
|
|---|---|---|---|
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Half-life of Biotinylated RBCs Among Participants Receiving Pathogen-Reduced RBC Unit
|
57.6 days
Standard Deviation 10.3
|
59.2 days
Standard Deviation 10.5
|
59.3 days
Standard Deviation 18.3
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OTHER_PRE_SPECIFIED outcome
Timeframe: Day 28 to Day 112Population: This analysis includes the 6 individuals participating in the optional study using pathogen-reduced treatment.
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.
Outcome measures
| Measure |
Biotin Labeled Red Blood Cells
n=6 Participants
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.
|
Red Blood Cell Unit After Pathogen-Reduced Treatment
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with biotin labeled red blood cells (RBCs), after the pathogen-reduced treatment via the INTERCEPT Blood System.
|
Conventional RBC Unit
n=6 Participants
Participants are persons with sickle cell disease (SCD) receiving a blood transfusion with a conventional RBC unit.
|
|---|---|---|---|
|
Estimated Time to RBC Clearance Among Participants Receiving Pathogen-Reduced RBC Unit
|
115.1 days
Standard Deviation 7.2
|
104.4 days
Standard Deviation 4.7
|
115.1 days
Standard Deviation 9.8
|
Adverse Events
Biotin Labeled Red Blood Cells
Serious events: 12 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Biotin Labeled Red Blood Cells
n=22 participants at risk
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.
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). 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 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. This optional study activity examines the survival of transfused RBCs with and without the INTERCEPT treatment.
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|---|---|
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Blood and lymphatic system disorders
Vaso-occlusive pain episode
|
31.8%
7/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
|
Immune system disorders
Fever
|
18.2%
4/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
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Hepatobiliary disorders
Biliary stricture with cholangitis
|
4.5%
1/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
Other adverse events
| Measure |
Biotin Labeled Red Blood Cells
n=22 participants at risk
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.
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). 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 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. This optional study activity examines the survival of transfused RBCs with and without the INTERCEPT treatment.
|
|---|---|
|
Immune system disorders
Antibodies to B-RBC
|
13.6%
3/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
|
Immune system disorders
New RBC autoantibody detection
|
4.5%
1/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
|
Immune system disorders
Allergic reaction to subsequent transfusion
|
4.5%
1/22 • Information on adverse events was collected from the time of transfusion and continued through the final assessment (up to 6 months).
Participants were monitored closely during the blood transfusion for adverse events. Laboratory monitoring for events of special interest/hemolytic transfusion reactions was performed at Day 1 (24 hours) and weekly through Week 4. Adverse events for the detection of anti-BioRBC antibodies and INTERCEPT RBC antibodies were monitored up to Month 6.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place