Sickle Cell Disease
Conditions
Keywords
SelG1, P-selectin, monoclonal antibody, sickle cell disease, sickle cell anemia, sickle cell, pain crisis, pain crises, vasoocclusion, vaso-occlusion, priapism, hepatic sequestration, splenic sequestration, chest syndrome, SCD
Brief summary
The purpose of this study was to determine whether the investigational drug SelG1 when given to sickle cell disease patients either taking or not taking hydroxyurea was effective in preventing or reducing the occurrence of pain crises. SelG1 prevents various cells in the bloodstream from sticking together. By stopping these cell-cell interactions, SelG1 may prevent small blood vessels from becoming blocked and therefore reduce the occurrence and severity of pain crises. Other effects of SelG1 was evaluated, as well as the safety of the drug and how long it stayed in the blood stream. Funding Source - FDA Office of Orphan Products Development (OOPD)
Interventions
DRUGSelG1
DRUGPlacebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Food and Drug Administration (FDA)
Reprixys Pharmaceutical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Sickle Cell Disease (HbSS, HbSC, HbSβ⁰-thalassemia, or HbSβ⁺-thalassemia) * If receiving hydroxyurea or erythropoietin, treatment must have been prescribed for at least 6 months, with the dose stable for at least 3 months * Between 2 and 10 sickle cell-related pain crises in the past 12 months Key
Exclusion criteria
* On a chronic transfusion program or planning on exchange transfusion during the study * Hemoglobin \<4.0 g/dL * Planned initiation, termination, or dose alteration of hydroxyurea during the study * Receiving chronic anticoagulation therapy (e.g. warfarin, heparin) other than aspirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median | One year | An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year. |
| Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median | One year | An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Second Sickle Cell-related Pain Crisis | Up to one year | Time to second SCPC is defined as months from randomization to second SCPC. A patient with less than two SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For patients never dosed, the end date is the end of study date. |
| Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median | Up to one year | Uncomplicated SCPC is defined as an acute episode of pain with no known cause for pain other than a vasoocclusive event; requiring a visit to a medical facility; and requiring treatment with a parenteral or oral narcotic (including opiates), or parenteral NSAIDs; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism. |
| Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median | One year | The annual rate of days hospitalized was calculated as the number of days hospitalized multiplied by 365 divided by the end date minus the date of randomization plus one where the end date is defined as the last dose date plus 14 days (for subjects never dosed, the end date equaled the end of study date, which was the last site contact for these patients). |
| Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Baseline, Day 15, Week 14, Week 26, Week 38, Week 52, and Week 58, up to 58 weeks | The BPI instrument was completed by the patients at pre-specified study visits prior to & during the Treatment & Follow-Up Evaluation Phases. Patients completed the brief pain inventory long-form, 1-week recall at the indicated pre-specified study visits. The BPI is a standardized self-reported questionnaire developed to provide information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI also asks questions about pain relief, pain quality, & the patient's perception of the cause of pain. Since pain can be quite variable over a day, the BPI asks patients to rate their pain at the time of responding to the questionnaire (pain now), & also at its worst, least, & average over the previous week. The scorings for pain & interference have a range from 0 (no pain/no interference) to 10 (worst pain/complete interference). The BPI scoring manual was used to calculate scores for each domain. |
| Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median | One year | Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: a participant had to have reported chest pain, a temperature of more than 38.5oC, tachypnea, wheezing or cough. |
| Time to First Sickle Cell-related Pain Crisis | Up to one year | Time to first SCPC is defined as months from randomization to first SCPC. A participant without SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For participants never dosed, the end date is the end of study date. |
Countries
Brazil, Jamaica, United States
Participant flow
Recruitment details
Approx. 174 patients were planned. A total of 198 patients were randomized. 192 patients received at least 1 dose of study drug & were analyzed for safety; 198 patients were analyzed for efficacy, 125 patients contributed data to the analysis of SelG1 PK data, & 176 patients contributed data to the analysis of PD data (% P-selectin inhibition).
Pre-assignment details
The study included a Screening Phase, Treatment Phase, and Follow-up Evaluation Phase. During the Screening Phase, potential study participants were to be fully screened for both inclusion and exclusion criteria before and undergo clinical and laboratory evaluations within 30 days prior to randomization into the study.
Participants by arm
| Arm | Count |
|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) IV Infusion, once every 4 weeks through Week 50
SelG1 | 67 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) IV Infusion, once every 4 weeks through Week 50
SelG1 | 66 |
| Placebo IV Infusion, once every 4 weeks through Week 50
Placebo | 65 |
| Total | 198 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 3 |
| Overall Study | Death | 2 | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 4 | 6 |
| Overall Study | Non-compliance with study | 1 | 3 | 1 |
| Overall Study | Physician Decision | 2 | 2 | 2 |
| Overall Study | Reasons different from categories above | 7 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 7 | 6 | 6 |
Baseline characteristics
| Characteristic | High-dose SelG1 (Selg1 5.0 mg/kg) | Low-dose SelG1 (Selg1 2.5 mg/kg) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 30.9 years STANDARD_DEVIATION 10.89 | 30.1 years STANDARD_DEVIATION 9.79 | 29.3 years STANDARD_DEVIATION 10.36 | 30.1 years STANDARD_DEVIATION 10.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 12 Participants | 11 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants | 52 Participants | 53 Participants | 150 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 60 participants | 62 participants | 60 participants | 182 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 2 participants | 7 participants |
| Race/Ethnicity, Customized White | 4 participants | 2 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 35 Participants | 36 Participants | 38 Participants | 109 Participants |
| Sex: Female, Male Male | 32 Participants | 30 Participants | 27 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 66 | 1 / 64 | 2 / 62 |
| other Total, other adverse events | 46 / 66 | 47 / 64 | 42 / 62 |
| serious Total, serious adverse events | 17 / 66 | 21 / 64 | 17 / 62 |
Outcome results
Primary
Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median
An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year.
Time frame: One year
Population: Intent-to-Treat (ITT) population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median | 1.63 SCPC per year |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median | 2.01 SCPC per year |
| Placebo | Annual Rate of Sickle Cell-related Pain Crises (SCPC) Per Hodges-Lehmann Median | 2.98 SCPC per year |
p-value: =0.0195% CI: [-2, 0]Stratified Wilcoxon Rank Sum Test
p-value: =0.1895% CI: [-1.84, 0.02]Stratified Wilcoxon Rank Sum Test
Primary
Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median
An SCPC is defined as an acute episode of pain with no other medically determined cause than a vasoocclusive event that requires a medical facility visit and treatment with oral or parenteral narcotics, or parenteral non-steroidal anti-inflammatory drugs. The annual rate of SCPC is defined as the total number of pain crises for a patient occurring from the date of randomization to the end date multiplied by 365 divided by the number of days during that same time period. End date is defined as the last dose date plus 14 days. For participants never dosed, the end date was the end of study date. This calculation accounts for early dropouts or lost to follow-up by extrapolating the SCPC rate of every participant to one year.
Time frame: One year
Population: Intent-to-Treat (ITT) population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median | 1.63 SCPC per year |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median | 2.01 SCPC per year |
| Placebo | Annual Rate of Sickle Cell-related Pain Crises (SCPC) - Per Standard Median | 2.98 SCPC per year |
Secondary
Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median
Acute Chest Syndrome (ACS) is defined on the basis of the finding of a new pulmonary infiltrate involving at least one complete lung segment that was consistent with alveolar consolidation, but excluding atelectasis (as indicated by chest X-ray). At least one of the following additional signs or symptoms needs to be present as well: a participant had to have reported chest pain, a temperature of more than 38.5oC, tachypnea, wheezing or cough.
Time frame: One year
Population: ITT population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median | 0.00 accute chest syndrome per year |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median | 0.00 accute chest syndrome per year |
| Placebo | Annual Rate of Acute Chest Syndrome Per Hodges-Lehmann Median | 0.00 accute chest syndrome per year |
p-value: =0.7895% CI: [0, 0]Stratified Wilcoxon Rank Sum test
p-value: =0.86895% CI: [0, 0]Stratified Wilcoxon Rank Sum test
Secondary
Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median
The annual rate of days hospitalized was calculated as the number of days hospitalized multiplied by 365 divided by the end date minus the date of randomization plus one where the end date is defined as the last dose date plus 14 days (for subjects never dosed, the end date equaled the end of study date, which was the last site contact for these patients).
Time frame: One year
Population: ITT: The ITT population includes all randomized patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median | 4.00 Days hospitalized per year |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median | 6.87 Days hospitalized per year |
| Placebo | Annual Rate of Days Hospitalized (Key Secondary Endpoint) Per Hodges-Lehmann Median | 6.87 Days hospitalized per year |
p-value: =0.4595% CI: [-4.36, 0]Stratified Wilcoxon Rank Sum Test
p-value: =0.83795% CI: [-3.9, 2.61]Stratified Wilcoxon Rank Sum Test
Secondary
Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median
Uncomplicated SCPC is defined as an acute episode of pain with no known cause for pain other than a vasoocclusive event; requiring a visit to a medical facility; and requiring treatment with a parenteral or oral narcotic (including opiates), or parenteral NSAIDs; but is NOT classified as an acute chest syndrome, hepatic sequestration, splenic sequestration or priapism.
Time frame: Up to one year
Population: ITT population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median | 1.08 Uncomplicated SCPC per year |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median | 2.00 Uncomplicated SCPC per year |
| Placebo | Annual Rate of Uncomplicated Sickle Cell-related Pain Crisis Per Hodges-Lehmann Median | 2.91 Uncomplicated SCPC per year |
p-value: =0.01595% CI: [-1.98, 0]Stratified Wilcoxon Rank Sum Test
p-value: =0.1295% CI: [-1.77, 0]Stratified Wilcoxon Rank Sum Test
Secondary
Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire
The BPI instrument was completed by the patients at pre-specified study visits prior to & during the Treatment & Follow-Up Evaluation Phases. Patients completed the brief pain inventory long-form, 1-week recall at the indicated pre-specified study visits. The BPI is a standardized self-reported questionnaire developed to provide information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The BPI also asks questions about pain relief, pain quality, & the patient's perception of the cause of pain. Since pain can be quite variable over a day, the BPI asks patients to rate their pain at the time of responding to the questionnaire (pain now), & also at its worst, least, & average over the previous week. The scorings for pain & interference have a range from 0 (no pain/no interference) to 10 (worst pain/complete interference). The BPI scoring manual was used to calculate scores for each domain.
Time frame: Baseline, Day 15, Week 14, Week 26, Week 38, Week 52, and Week 58, up to 58 weeks
Population: ITT population: The ITT population includes all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 26 (n=27,31,32) | -0.377 score on a scale | Standard Deviation 1.246 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 38 (n=25,29,29) | -0.866 score on a scale | Standard Deviation 2.772 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: Baseline (BL) (n=48,49,55) | 4.363 score on a scale | Standard Deviation 2.1176 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Day 15 (n=38,42,47) | -0.123 score on a scale | Standard Deviation 1.3419 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week (Wk) 14 (n=32,33,33) | -0.146 score on a scale | Standard Deviation 1.152 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 38 (n=25,29,29) | -0.267 score on a scale | Standard Deviation 1.4079 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 52 (n=18,23,22) | -0.634 score on a scale | Standard Deviation 1.8501 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Wk 58 follow up (n=27,33,30) | -0.145 score on a scale | Standard Deviation 1.2309 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: BL (n=48,49,55) | 4.643 score on a scale | Standard Deviation 2.5726 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Day 15 (n=38,42,47) | -0.674 score on a scale | Standard Deviation 2.2868 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Wk 14 (n=32,33,33) | -0.213 score on a scale | Standard Deviation 2.3988 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 26 (n=27,32,32) | -0.583 score on a scale | Standard Deviation 2.2844 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 52 (n=18,23,22) | -1.014 score on a scale | Standard Deviation 2.0989 |
| High-dose SelG1 (Selg1 5.0 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 58 f/up (n=27,33,30) | -0.476 score on a scale | Standard Deviation 2.3473 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 38 (n=25,29,29) | -0.119 score on a scale | Standard Deviation 1.6473 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Wk 14 (n=32,33,33) | -0.534 score on a scale | Standard Deviation 2.7769 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Day 15 (n=38,42,47) | 0.073 score on a scale | Standard Deviation 1.5097 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 58 f/up (n=27,33,30) | -0.386 score on a scale | Standard Deviation 2.2249 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: Baseline (BL) (n=48,49,55) | 4.531 score on a scale | Standard Deviation 2.0089 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: BL (n=48,49,55) | 4.656 score on a scale | Standard Deviation 2.6099 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 52 (n=18,23,22) | 0.130 score on a scale | Standard Deviation 1.5899 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 26 (n=27,32,32) | -0.728 score on a scale | Standard Deviation 2.422 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week (Wk) 14 (n=32,33,33) | -0.068 score on a scale | Standard Deviation 1.4608 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 52 (n=18,23,22) | -0.174 score on a scale | Standard Deviation 2.251 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Day 15 (n=38,42,47) | -0.099 score on a scale | Standard Deviation 2.0435 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 26 (n=27,31,32) | -0.290 score on a scale | Standard Deviation 1.9865 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Wk 58 follow up (n=27,33,30) | 0.091 score on a scale | Standard Deviation 1.379 |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 38 (n=25,29,29) | 0.026 score on a scale | Standard Deviation 1.3893 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 26 (n=27,32,32) | -0.821 score on a scale | Standard Deviation 3.1561 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 38 (n=25,29,29) | 0.333 score on a scale | Standard Deviation 1.843 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 52 (n=18,23,22) | -0.310 score on a scale | Standard Deviation 1.9508 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 38 (n=25,29,29) | -0.221 score on a scale | Standard Deviation 3.1076 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Wk 58 follow up (n=27,33,30) | -0.444 score on a scale | Standard Deviation 1.8626 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: BL (n=48,49,55) | 4.995 score on a scale | Standard Deviation 2.947 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Day 15 (n=38,42,47) | -0.816 score on a scale | Standard Deviation 2.3556 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 52 (n=18,23,22) | -0.819 score on a scale | Standard Deviation 2.849 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interence: CFB to Wk 14 (n=32,33,33) | -0.039 score on a scale | Standard Deviation 3.0412 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Interference: CFB to Wk 58 f/up (n=27,33,30) | -0.802 score on a scale | Standard Deviation 2.5785 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Day 15 (n=38,42,47) | 0.355 score on a scale | Standard Deviation 1.7289 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week (Wk) 14 (n=32,33,33) | -0.152 score on a scale | Standard Deviation 2.0918 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: Baseline (BL) (n=48,49,55) | 4.129 score on a scale | Standard Deviation 2.0076 |
| Placebo | Patient Reported Outcome: Change From Baseline in Pain Severity/Pain Interference Domain From Brief Pain Inventory (BPI) Questionnaire | Pain Severity: CFB to Week 26 (n=27,31,32) | -0.563 score on a scale | Standard Deviation 2.3751 |
Secondary
Time to First Sickle Cell-related Pain Crisis
Time to first SCPC is defined as months from randomization to first SCPC. A participant without SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For participants never dosed, the end date is the end of study date.
Time frame: Up to one year
Population: ITT population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Time to First Sickle Cell-related Pain Crisis | 4.07 months |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Time to First Sickle Cell-related Pain Crisis | 2.20 months |
| Placebo | Time to First Sickle Cell-related Pain Crisis | 1.38 months |
p-value: =0.00195% CI: [0.331, 0.741]Log Rank
p-value: =0.13695% CI: [0.515, 1.097]Log Rank
Secondary
Time to Second Sickle Cell-related Pain Crisis
Time to second SCPC is defined as months from randomization to second SCPC. A patient with less than two SCPC before withdrawal or completion of the study is considered censored at the time of the end date. End date is defined as the last dose plus 14 days. For patients never dosed, the end date is the end of study date.
Time frame: Up to one year
Population: ITT population: The ITT population includes all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| High-dose SelG1 (Selg1 5.0 mg/kg) | Time to Second Sickle Cell-related Pain Crisis | 10.32 months |
| Low-dose SelG1 (Selg1 2.5 mg/kg) | Time to Second Sickle Cell-related Pain Crisis | 9.20 months |
| Placebo | Time to Second Sickle Cell-related Pain Crisis | 5.09 months |
p-value: =0.02295% CI: [0.329, 0.866]Log Rank
p-value: =0.195% CI: [0.44, 1.092]Log Rank