Trial Outcomes & Findings for A Phase II Trial of Regadenoson in Sickle Cell Anemia (NCT NCT01788631)

Last Updated: 2018-02-07

Results Overview

To determine if infusional Regadenoson reduced iNKT cell activation among individuals with sickle cell anemia (SCA) and pain or acute chest syndrome (ACS) compared to placebo by 70% or greater.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Baseline-End of study infusion over 48 hours

Results posted on

2018-02-07

Participant Flow

Between July 2013 and November 2016, 4,940 hospital admissions were screened to enroll 100 study subjects. Patients were recruited at the time of sickle cell vaso-occlusive crises in outpatient clinics, emergency departments, and inpatient units.

Prior to study arm randomization and assignment, patients were screened using the following testing methods: Confirmation of sickle cell genotype, complete blood count with differential, chemistry, coagulation testing (Including PTT, and INR), and pregnancy testing for female participants.

Participant milestones

Participant milestones
Measure	Regadenoson Arm 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Overall Study STARTED	52	44
Overall Study Randomized	53	47
Overall Study COMPLETED	49	43
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Trial of Regadenoson in Sickle Cell Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regadenoson Arm n=53 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=47 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.	Total n=100 Participants Total of all reporting groups
Age, Continuous	25 years n=99 Participants	26 years n=107 Participants	25 years n=206 Participants
Sex: Female, Male Female	22 Participants n=99 Participants	24 Participants n=107 Participants	46 Participants n=206 Participants
Sex: Female, Male Male	31 Participants n=99 Participants	23 Participants n=107 Participants	54 Participants n=206 Participants
Region of Enrollment United States	53 Participants n=99 Participants	47 Participants n=107 Participants	100 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: Treated patients with baseline and end of infusion blood samples.

To determine if infusional Regadenoson reduced iNKT cell activation among individuals with sickle cell anemia (SCA) and pain or acute chest syndrome (ACS) compared to placebo by 70% or greater.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Number of Participants With a Reduction in Invariant Natural-Killer T-Cell (iNKT Cell) Activation by 70% or More	21 Participants	10 Participants

SECONDARY outcome

Timeframe: Hospital Presentation- Hospital Discharge, assessed up to 1 month

Population: All patients who had baseline and end of infusion blood samples.

To determine if regadenoson reduces length of hospital stay among individuals admitted with SCA and pain or ACS compared to placebo

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Length of Hospital Stay	3.96 Days Interval 2.23 to 19.25	3.99 Days Interval 2.34 to 30.4

SECONDARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: All patients who had baseline and end of infusion blood samples.

To determine if regadenoson improved respiratory symptoms among individuals with sickle cell anemia (SCA) and pain or acute chest syndrome (ACS) compared to placebo. Patients were classified as having an improvement in respiratory symptoms if they experienced any of the following outcomes:(1) respiratory rate decreased by 25% from baseline or normalized (≤20 bpm) or (2) degree of hypoxia (SpO2) on room air increased by 10% from baseline or normalized (≥92%) or (3) thoracic pain improved by 3 points from baseline on a 10-point visual analog scale.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Number of Participants With an Improvement in Respiratory Symptoms	10 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: All patients who had baseline and end of infusion blood samples.

To determine if regadenoson reduces opioid use among individuals with SCA and pain or ACS compared to placebo.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Opioid Use	0.03 mg/kg/hr Interval 0.0 to 0.5	0.04 mg/kg/hr Interval 0.0 to 0.36

SECONDARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: All patients who had baseline and end of infusion blood samples.

To determine if regadenoson reduces levels of inflammatory markers among individuals with SCA and pain or ACS compared to placebo.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Level of Inflammatory Markers (A2A)	86.39 A2A levels as percent of baseline Interval 35.3 to 316.67	100.95 A2A levels as percent of baseline Interval 17.44 to 404.66

SECONDARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: All patients who had baseline and end of infusion blood samples.

To determine if regadenoson reduces levels of inflammatory markers among individuals with SCA and pain or ACS compared to placebo.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Level of Inflammatory Markers (IL-4)	85.89 IL-4 levels as percent of baseline Interval 33.51 to 389.76	100.91 IL-4 levels as percent of baseline Interval 17.35 to 351.09

SECONDARY outcome

Timeframe: Baseline-End of study infusion over 48 hours

Population: All patients who had baseline and end of treatment samples

To determine if regadenoson reduces levels of inflammatory markers among individuals with SCA and pain or ACS compared to placebo.

Outcome measures

Outcome measures
Measure	Regadenoson Arm n=49 Participants 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=43 Participants Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Level of Inflammatory Markers (IFN-gamma)	97.38 IFN-gamma levels as percent of baseline Interval 42.5 to 293.83	105.66 IFN-gamma levels as percent of baseline Interval 28.01 to 420.99

Adverse Events

Regadenoson Arm

Serious events: 14 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 16 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. David G. Nathan

Dana-Farber Cancer Institute

Phone: 61746322155

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Regadenoson Arm n=52 participants at risk 1.44 mcg/kg/hour infused over 48 hours Regadenoson: Regadenoson is an A2AR agonist that is a coronary vasodilator. It is chemically described as adenosine, 2-\[4-\[(methylamino)carbonyl\]-1H-pyrazol-1-yl\]-, monohydrate. Its molecular formula is C15H18N8O5. Regadenoson has an FDA indication for use in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress. It has lower affinity for non-A2A adenosine receptor subtypes thought to be associated with some of the adverse effects associated with non-selective adenosine receptor agonists, which increase extracellular adenosine by blocking its uptake into cells. The maximal plasma concentration of regadenoson is achieved within 1 to 4 minutes after injection and parallels the onset of the pharmacodynamic response. Its half-life is approximately 2 to 4 minutes.	Placebo Arm n=44 participants at risk Placebo infused over 48 hours Placebo: This study uses 0.9% Normal Saline (NS) as placebo. This is a sterile sodium chloride solution usually used to replenish fluids and electrolytes. It contains no additives, and is a standard solution used as placebo in clinical trials where the study drug is administration intravenously. NS will be prepared by investigational pharmacy.
Gastrointestinal disorders Abdominal pain	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Blood and lymphatic system disorders Anemia	3.8% 2/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Musculoskeletal and connective tissue disorders Avascular necrosis	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Musculoskeletal and connective tissue disorders Back pain	7.7% 4/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	9.1% 4/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Investigations Blood bilirubin increased	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Cardiac disorders Chest pain - cardiac	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Gastrointestinal disorders Diarrhea	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
General disorders General disorders and administration site conditions - Other, specify	3.8% 2/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Nervous system disorders Headache	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Investigations Hemoglobin increased	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Investigations Neutrophil count decreased	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
General disorders Non-cardiac chest pain	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	4.5% 2/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
General disorders Pain	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	6.8% 3/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	13.5% 7/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	18.2% 8/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	2.3% 1/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.00% 0/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	4.5% 2/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.
Infections and infestations Tooth infection	1.9% 1/52 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.	0.00% 0/44 • Adverse events were assessed from the time patients presented to the emergency department for their vaso-occlusive crisis through 30 days post- hospital discharge. For this study, all adverse events Grade 3 and above were categorized as serious adverse events.