Sickle Cell Anemia
Conditions
Keywords
Sickle cell disease, hemoglobinopathy, pediatric
Brief summary
The study assesses the efficacy, safety and tolerability of ACZ885 (canakinumab) in pediatric and young adult patients with sickle cell anemia (SCA).
Detailed description
This was an ambulatory-based 24-week study followed by an additional 24-week open label phase. It was a subject- and investigator-blinded, randomized, placebo-controlled, parallel group, non-confirmatory study to assess the clinical efficacy of ACZ885 administered s.c. in six injections given 28 days apart (in each phase of the study). Pediatric and young adult subjects diagnosed with sickle cell anemia (SCA) were planned to be randomized to either ACZ885 treatment or placebo treatment in a 1:1 ratio,. For each subject, there was a maximum 28-day screening period that included recording of daily pain frequency and intensity by e-diary for at least 1 week. Subjects who met the eligibility criteria at screening underwent evaluation of baseline clinical and biomarker assessments prior to first dose administration. On Day 1, monthly s.c. dosing with ACZ885 started at 4 mg/kg for subjects weighing ≤40 kg and 300 mg for all other subjects. Subjects in the placebo treatment arm were injected with placebo in a like manner. All subjects returned to the study centers for safety checks on a monthly basis when they received treatment with either ACZ885 or placebo. The final blinded dosing was given on Week 20, followed by blinded clinical assessments at Week 24. Subjects from both study arms were then offered optional, open label monthly dosing of ACZ885 for an additional 24 weeks (Weeks 24-48) with clinical outcome assessment. Subjects returned for the end of study (EOS) visit at Week 56. For subjects who chose not to participate in the optional, open label portion of the study, or for those stopping treatment early for any other reason, an EOS visit occurred approximately 8 weeks after last dose received. After enrollment of 49 subjects, Novartis decided to terminate the study early due to strategic reasons not related to safety and decided that no additional enrollment was needed in order to interpret the study objectives.
Interventions
DRUGACZ885
Monthly doses of 4 mg/kg for subjects weighing ≤40 kg and 300 mg for all other subjects
DRUGPlacebo
Monthly doses of placebo to match the administered dose of canakinumab s.c.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 20 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ages 8-20 years of age (both inclusive) diagnosed with sickle cell anemia (HbSS) or sickle beta0 thalassemia (documented by family studies, or analysis of either hemoglobin or DNA). * Patient's written informed consent from those ≥18 years of age must be obtained before any assessment is performed. Parent or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for patients \< 18 years of age. * Detectable baseline of background or episodic pain measured by daily e-diary over 1 to 2 weeks during screening period as defined below: Average daily pain score ≥ 1 cm without analgesic use over a period of at least 7 days and/or, At least one episode of pain requiring analgesic use during a period of up to 14 days. * History of ≥2 vaso-occlusive pain episodes in the past year, as defined as pain with no other, non-sickle cell identifiable cause that requires analgesia and interferes with the patient's normal daily routine.
Exclusion criteria
* History of known hypersensitivity to canakinumab. * Ongoing or treatment with the past 3 months with red blood cell transfusion therapy, or have evidence of iron overload requiring chelation therapy. * Transcranial Doppler ultrasound in the past year or at screening in patients with an accessible transtemporal window, demonstrating velocity in middle or anterior cerebral or internal carotid artery ≥200 cm/sec. * Administration of any other blood products within 3 weeks of screening visit. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of 4- Week Average Daily Pain Measured by Visual Analog Score (VAS) Over the Period of Week 8 to 12 | Baseline (upto 28 days prior to start of treatment), Week 8 to 12 | Visual analog scale (VAS) was used to record severity. Pediatric and young adult participants rated their daily sickle cell associated pain intensity once each day in the evening using an 11-point numerical rating scale from 0 to 10 with higher ratings associated with more intense pain (0 = no pain, 10 = worst pain). For each subject, there was a maximum 28-day screening period that included recording of daily pain intensity by e-diary for at least 1 week. The average daily pain results in the screening period were used to derive the baseline value. The average over week 8 to 12 was calculated and the change from baseline in the average daily pain VAS was analyzed using a Bayesian model for repeated measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Concentration of High Sensitivity C-Reactive Protein (hsCRP) From Baseline to Week 12 | Baseline, Week 12 | hs-CRP is a biomarker that represents the inflammation process. |
| Change in the Concentration of White Blood Cell (WBC) Count From Baseline to Week 12 | Baseline, Week 12 | WBC count was used as a laboratory marker to determine the effect of the drug |
| Change in the Concentration of Absolute Count of Neutrophils From Baseline to Week 12 | Baseline, Week 12 | Absolute count of neutrophils was measured as a laboratory marker to determine the effect of the drug |
| Change in the Concentration of Absolute Count of Blood Monocytes From Baseline to Week 12 | Baseline, Week 12 | Absolute count of blood monocytes was measured as a laboratory marker to determine the effect of the drug. |
| Change in the Concentration of Hemoglobin From Baseline to Week 12 | Baseline, Week 12 | Hemoglobin was used as a hemolysis marker to determine the effect of the drug. |
| Change in the Reticulocyte Count From Baseline to Week 12 | Baseline, Week 12 | Reticulocyte count was used as a hemolysis marker to determine the effect of the drug |
| Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | Baseline (upto 28 days prior to start of treatment), Week 0 to 4, Week 4 to 8, Week 8 to 12, Week 12 to 16, Week 16 to 20 and Week 20 to 24 | Visual analog scale (VAS) was used to record severity. Pediatric and young adult participants rated their daily sickle cell associated pain intensity once each day in the evening using an 11-point numerical rating scale from 0 to 10 with higher ratings associated with more intense pain (0 = no pain, 10 = worst pain). The average of 4 weeks interval up to week 24 was calculated. |
| Change in the Concentration of Lactate Dehydrogenase (LDH) From Baseline to Week 12 | Baseline, Week 12 | LDH was used as a hemolysis marker to determine the effect of the drug |
| Change in the Concentration of Haptoglobin From Baseline to Week 12 | Baseline, Week 12 | Haptoglobin was used as a hemolysis marker to determine the effect of the drug |
| Change in the Concentration of Oxygen Percent Saturation (SAO2) From Baseline to Week 12 | Baseline, Week 12 | SAO2 was used as a hemolysis marker to determine the effect of the drug |
| Number of Days Absent From School or Work Due to Pain as Recorded by E-diary | up to Week 24 | The number of SCA-related days absent from school or work were derived from eDiary records. |
| Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | 12 weeks | The occurrence of acute blood transfusions was summarized as the proportion of subjects who received at least one acute blood transfusion and the event rate of acute blood transfusions per subject, by study period, group and reason of transfusion. |
| Mean Serum Concentration After Repeated Dosing of ACZ885 | Baseline, Week 4, 12, 20 and 24 | PK samples were collected at Baseline, Week 4, 12, 20 and 24. Mean and standard deviation of the ACZ885 concentration was reported. Only those participants available at the specified time points were analyzed |
| Change in the Concentration of Bilirubin From Baseline to Week 12 | Baseline, Week 12 | Bilirubin was used as a hemolysis marker to determine the effect of the drug |
Countries
Canada, Germany, Israel, South Africa, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A total of 49 participants were randomized into the study from 15 centers in seven countries: Greater Britain (5), Israel (1), Germany (1), Turkey (3), South Africa (1), USA (3) and Canada (1).
Pre-assignment details
Subjects who met the eligibility criteria at screening underwent evaluation of baseline clinical and biomarker assessments prior to first dose administration.
Participants by arm
| Arm | Count |
|---|---|
| ACZ885 Monthly doses of 4 mg/kg for subjects weighing ≤40 kg and 300 mg for all other subjects | 25 |
| Placebo Monthly doses of placebo to match the administered dose of ACZ885 s.c. | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Subject/Guardian Decision | 3 | 1 |
Baseline characteristics
| Characteristic | ACZ885 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 15.8 Years STANDARD_DEVIATION 2.69 | 15.6 Years STANDARD_DEVIATION 3.28 | 15.7 Years STANDARD_DEVIATION 2.97 |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 13 Participants | 25 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 10 Participants | 22 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 19 / 25 | 20 / 24 | 17 / 22 | 18 / 20 |
| serious Total, serious adverse events | 11 / 25 | 15 / 24 | 11 / 22 | 11 / 20 |
Outcome results
Primary
Change From Baseline of 4- Week Average Daily Pain Measured by Visual Analog Score (VAS) Over the Period of Week 8 to 12
Visual analog scale (VAS) was used to record severity. Pediatric and young adult participants rated their daily sickle cell associated pain intensity once each day in the evening using an 11-point numerical rating scale from 0 to 10 with higher ratings associated with more intense pain (0 = no pain, 10 = worst pain). For each subject, there was a maximum 28-day screening period that included recording of daily pain intensity by e-diary for at least 1 week. The average daily pain results in the screening period were used to derive the baseline value. The average over week 8 to 12 was calculated and the change from baseline in the average daily pain VAS was analyzed using a Bayesian model for repeated measures.
Time frame: Baseline (upto 28 days prior to start of treatment), Week 8 to 12
Population: Pharmacodynamics (PD) analysis set: included all subjects with available PD data, who received any study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change From Baseline of 4- Week Average Daily Pain Measured by Visual Analog Score (VAS) Over the Period of Week 8 to 12 | -0.45 Score on a scale | Standard Deviation 0.384 |
| Placebo | Change From Baseline of 4- Week Average Daily Pain Measured by Visual Analog Score (VAS) Over the Period of Week 8 to 12 | -0.37 Score on a scale | Standard Deviation 0.402 |
p-value: 0.5590% CI: [-1.03, 0.85]Bayesian model for repeated measures
Secondary
Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24
Visual analog scale (VAS) was used to record severity. Pediatric and young adult participants rated their daily sickle cell associated pain intensity once each day in the evening using an 11-point numerical rating scale from 0 to 10 with higher ratings associated with more intense pain (0 = no pain, 10 = worst pain). The average of 4 weeks interval up to week 24 was calculated.
Time frame: Baseline (upto 28 days prior to start of treatment), Week 0 to 4, Week 4 to 8, Week 8 to 12, Week 12 to 16, Week 16 to 20 and Week 20 to 24
Population: Pharmacodynamics (PD) analysis set: included all subjects with available PD data, who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 0-4 Weeks | -0.337 Score on a scale | Standard Deviation 1.629 |
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 4-8 Weeks | -0.173 Score on a scale | Standard Deviation 1.515 |
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 8-12 Weeks | -0.444 Score on a scale | Standard Deviation 1.437 |
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 12-16 Weeks | -0.505 Score on a scale | Standard Deviation 1.744 |
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 16-20 Weeks | -0.388 Score on a scale | Standard Deviation 1.772 |
| ACZ885 | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 20-24 Weeks | -0.752 Score on a scale | Standard Deviation 1.678 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 16-20 Weeks | 0.151 Score on a scale | Standard Deviation 1.811 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 0-4 Weeks | 0.007 Score on a scale | Standard Deviation 1.428 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 12-16 Weeks | 0.057 Score on a scale | Standard Deviation 2.371 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 4-8 Weeks | 0.158 Score on a scale | Standard Deviation 1.847 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 20-24 Weeks | 0.036 Score on a scale | Standard Deviation 2.131 |
| Placebo | Change From Baseline of Average Daily Pain VAS Over 4 Weeks Intervals up to Week 24 | 8-12 Weeks | -0.376 Score on a scale | Standard Deviation 2.104 |
Secondary
Change in the Concentration of Absolute Count of Blood Monocytes From Baseline to Week 12
Absolute count of blood monocytes was measured as a laboratory marker to determine the effect of the drug.
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| ACZ885 | Change in the Concentration of Absolute Count of Blood Monocytes From Baseline to Week 12 | 0.712 10^9 cells/liter |
| Placebo | Change in the Concentration of Absolute Count of Blood Monocytes From Baseline to Week 12 | 0.992 10^9 cells/liter |
p-value: 0.03290% CI: [0.556, 0.925]Mixed-effect Model for Repeated Measures
Secondary
Change in the Concentration of Absolute Count of Neutrophils From Baseline to Week 12
Absolute count of neutrophils was measured as a laboratory marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| ACZ885 | Change in the Concentration of Absolute Count of Neutrophils From Baseline to Week 12 | 0.717 10^9 cells/liter |
| Placebo | Change in the Concentration of Absolute Count of Neutrophils From Baseline to Week 12 | 1.052 10^9 cells/liter |
p-value: 0.00490% CI: [0.547, 0.849]Mixed-effect Model for Repeated Measures
Secondary
Change in the Concentration of Bilirubin From Baseline to Week 12
Bilirubin was used as a hemolysis marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Concentration of Bilirubin From Baseline to Week 12 | 5.05 umol/L | Standard Deviation 19.796 |
| Placebo | Change in the Concentration of Bilirubin From Baseline to Week 12 | -1.95 umol/L | Standard Deviation 11.591 |
Secondary
Change in the Concentration of Haptoglobin From Baseline to Week 12
Haptoglobin was used as a hemolysis marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Concentration of Haptoglobin From Baseline to Week 12 | -0.0112 g/L | Standard Deviation 0.04022 |
| Placebo | Change in the Concentration of Haptoglobin From Baseline to Week 12 | -0.0213 g/L | Standard Deviation 0.07923 |
Secondary
Change in the Concentration of Hemoglobin From Baseline to Week 12
Hemoglobin was used as a hemolysis marker to determine the effect of the drug.
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Concentration of Hemoglobin From Baseline to Week 12 | -0.97 g/L | Standard Deviation 4.727 |
| Placebo | Change in the Concentration of Hemoglobin From Baseline to Week 12 | 1.11 g/L | Standard Deviation 7.975 |
Secondary
Change in the Concentration of High Sensitivity C-Reactive Protein (hsCRP) From Baseline to Week 12
hs-CRP is a biomarker that represents the inflammation process.
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| ACZ885 | Change in the Concentration of High Sensitivity C-Reactive Protein (hsCRP) From Baseline to Week 12 | 0.338 mg/L |
| Placebo | Change in the Concentration of High Sensitivity C-Reactive Protein (hsCRP) From Baseline to Week 12 | 0.830 mg/L |
p-value: 0.00290% CI: [0.253, 0.658]Mixed-effect Model for Repeated Measures
Secondary
Change in the Concentration of Lactate Dehydrogenase (LDH) From Baseline to Week 12
LDH was used as a hemolysis marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Concentration of Lactate Dehydrogenase (LDH) From Baseline to Week 12 | 19.06 Units per liter (U/L) | Standard Deviation 70.862 |
| Placebo | Change in the Concentration of Lactate Dehydrogenase (LDH) From Baseline to Week 12 | -33.74 Units per liter (U/L) | Standard Deviation 209.259 |
Secondary
Change in the Concentration of Oxygen Percent Saturation (SAO2) From Baseline to Week 12
SAO2 was used as a hemolysis marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Concentration of Oxygen Percent Saturation (SAO2) From Baseline to Week 12 | -0.5 Oxygen Saturation Percent | Standard Deviation 2.16 |
| Placebo | Change in the Concentration of Oxygen Percent Saturation (SAO2) From Baseline to Week 12 | -0.3 Oxygen Saturation Percent | Standard Deviation 1.82 |
Secondary
Change in the Concentration of White Blood Cell (WBC) Count From Baseline to Week 12
WBC count was used as a laboratory marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| ACZ885 | Change in the Concentration of White Blood Cell (WBC) Count From Baseline to Week 12 | 0.813 10^9 cells/liter |
| Placebo | Change in the Concentration of White Blood Cell (WBC) Count From Baseline to Week 12 | 1.081 10^9 cells/liter |
p-value: <0.00190% CI: [0.657, 0.862]Mixed-effect Model for Repeated Measures
Secondary
Change in the Reticulocyte Count From Baseline to Week 12
Reticulocyte count was used as a hemolysis marker to determine the effect of the drug
Time frame: Baseline, Week 12
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACZ885 | Change in the Reticulocyte Count From Baseline to Week 12 | -6.578 10^9 cells/liter | Standard Deviation 64.1131 |
| Placebo | Change in the Reticulocyte Count From Baseline to Week 12 | 25.358 10^9 cells/liter | Standard Deviation 47.6483 |
Secondary
Mean Serum Concentration After Repeated Dosing of ACZ885
PK samples were collected at Baseline, Week 4, 12, 20 and 24. Mean and standard deviation of the ACZ885 concentration was reported. Only those participants available at the specified time points were analyzed
Time frame: Baseline, Week 4, 12, 20 and 24
Population: Pharmacokinetics (PK) analysis set consisted of ACZ885 treated patients. Placebo patients were excluded from the PK analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ACZ885 | Mean Serum Concentration After Repeated Dosing of ACZ885 | Baseline | 0 ng/mL | Standard Deviation 0 |
| ACZ885 | Mean Serum Concentration After Repeated Dosing of ACZ885 | Week 4 | 13100 ng/mL | Standard Deviation 5490 |
| ACZ885 | Mean Serum Concentration After Repeated Dosing of ACZ885 | Week 12 | 18700 ng/mL | Standard Deviation 5860 |
| ACZ885 | Mean Serum Concentration After Repeated Dosing of ACZ885 | Week 20 | 19700 ng/mL | Standard Deviation 5810 |
| ACZ885 | Mean Serum Concentration After Repeated Dosing of ACZ885 | Week 24 | 20600 ng/mL | Standard Deviation 5930 |
Secondary
Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period
The occurrence of acute blood transfusions was summarized as the proportion of subjects who received at least one acute blood transfusion and the event rate of acute blood transfusions per subject, by study period, group and reason of transfusion.
Time frame: 12 weeks
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 2 transfusions | 0 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 2 transfusions | 1 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 3 transfusions | 0 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 3 transfusions | 0 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 0 transfusions | 22 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 0 transfusions | 23 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 1 transfusion | 2 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 1 transfusion | 4 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 2 transfusions | 1 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 1 transfusion | 2 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 3 transfusions | 0 Participants |
| ACZ885 | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 0 transfusions | 20 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 3 transfusions | 0 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 0 transfusions | 18 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 1 transfusion | 4 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 3 transfusions | 1 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 0 transfusions | 19 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 1 transfusion | 4 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 2 transfusions | 1 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Rescue | 3 transfusions | 0 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 0 transfusions | 22 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 1 transfusion | 1 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Acute blood transfusion: Prophylactic | 2 transfusions | 1 Participants |
| Placebo | Number of Acute Blood Transfusions Per Patient by Study Period - Double-blind Period | Overall Acute blood transfusion | 2 transfusions | 1 Participants |
Secondary
Number of Days Absent From School or Work Due to Pain as Recorded by E-diary
The number of SCA-related days absent from school or work were derived from eDiary records.
Time frame: up to Week 24
Population: Pharmacodynamics (PD) analysis including patients with a valid measurements for the outcome measure
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ACZ885 | Number of Days Absent From School or Work Due to Pain as Recorded by E-diary | 2.20 Days |
| Placebo | Number of Days Absent From School or Work Due to Pain as Recorded by E-diary | 1.86 Days |
p-value: 0.45590% CI: [0.58, 3.4]Generalized Linear Model (GLM)