| Primary | Double-Blind Period: Percentage of Participants Who Achieved Hemoglobin (Hb) Response From Week 12 Through Week 24 Compared With Baseline | Hb response is defined as ≥10 grams/ liter (g/L) (1.0 gram per deciliter) (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline. Hb response was tested using the Mantel-Haenszel stratum weighted method adjusting for randomization stratification factors. Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. | Posted | | Number | | Percentage of participants | | Double-Blind Period: Baseline up to Week 12 through Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
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| The estimated adjusted difference in response rate, 95% CI, and p-value are based on Mantel-Haenszel stratum weighted method adjusting for the randomization stratification factors. | Cochran-Mantel-Haenszel | | <0.0001 | | Percentage difference | 40.9 | | | 2-Sided | 95 | 32.0 | 49.8 | | | | | Superiority | | |
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| Secondary | Double-Blind Period: Change From Baseline in Average Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue Subscale Score From Week 12 Through Week 24 | The FACIT-Fatigue subscale includes a 13-item self-reported fatigue subscale, which assesses the severity and impact of fatigue (including the impact on daily activities and functioning).The FACIT-Fatigue subscale is scored on a 5-point Likert scale: 0 (not at all) to 4 (very much). The total FACIT-Fatigue subscale score ranges from 0 to 52, with a higher score indicating better health-related quality of life (HRQOL). Baseline is defined as the last assessment before randomization for subjects randomized and not dosed or the last assessment before start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | score on a scale | | Double-Blind Period: Baseline, Week 12 through Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Average Hb Concentration From Week 12 Through Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Gram per Liter (g/L) | | Double-Blind Period: Baseline, Week 12 through Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Percentage of Participants Who Achieved Hb 1.5+ Response From Week 12 Through Week 24 Compared With Baseline | Hb 1.5+ response is defined as a ≥1.5 g/dL increase in average Hb concentration from Week 12 through Week 24 compared with baseline. Hb 1.5+ response will be summarized using the Mantel-Haenszel stratum weighted method adjusting for randomization stratification factors. Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. | Posted | | Number | | Percentage of participants | | Double-Blind Period: Baseline up to Week 12 through Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Indirect Bilirubin at Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Micromole per Liter (umol/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Units per Liter (U/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Haptoglobin at Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Gram per Liter (g/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Reticulocytes at Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | 10^9 cells per liter (10^9 cells/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Erythropoietin at Week 24 | Baseline is defined as the average of all assessments within 42 days before randomization for subjects randomized and not dosed or within 42 days before the start of study treatment for subjects randomized and dosed. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | International units per Liter (IU/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Percentage of Participants Who Achieved Patient Global Impression of Severity (PGIS)- Fatigue Response at Weeks 12, 16, 20, and 24 | PGIS-Fatigue measured participants' perception of their fatigue severity (7-day recall) on a 4-point scale ranging from '1=none' to '4=severe'. A participant was considered to have achieved the PGIS-Fatigue response at Weeks 12, 16, 20, or 24, if their baseline to postbaseline score met one of the following conditions: 'none' at baseline to 'none' postbaseline; 'mild' to 'mild' or 'none'; 'moderate' to 'mild' or 'none'; or 'severe' to 'moderate', 'mild', or 'none'. | FAS included all participants who were randomized. | Posted | | Number | | percentage of participants | | Double-Blind Period: At Weeks 12, 16, 20, and 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Percentage of Participants Who Achieved the Patient Global Impression of Change (PGIC)- Fatigue Response at Weeks 12, 16, 20, and 24 | The PGIC-Fatigue assesses change over time compared with baseline on a 5-point scale ranging from 0 to 4 where 0 indicates Much better and 4 as Much worse. A participant was considered to have achieved the PGIC-Fatigue response at Weeks 12, 16, 20, or 24 if their baseline PGIS and corresponding PGIC met one of the following conditions: if the PGIS at baseline was 'none' or 'mild' and PGIC at the visit was 'no change', 'a little better', or 'much better'; or if the PGIS at baseline was 'moderate' or 'severe' and PGIC at the visit was 'a little better' or 'much better'. | FAS included all participants who were randomized. | Posted | | Number | | percentage of participants | | Double-Blind Period: At Weeks 12, 16, 20, and 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for 5 up to years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 24 | The 6MWT is a well-established performance outcome (PerfO) measure that is widely used to evaluate physical activity in terms of distance walked in patients with a variety of conditions. The test measures the distance an individual can walk on a hard, flat surface in 6 minutes. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Meters | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Serum Ferritin at Week 24 | Iron metabolism was assessed based on serum ferritin levels. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Microgram/Liter (mcg/L) | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Change From Baseline in Transferrin Saturation (TSAT) at Week 24 | Iron metabolism was assessed based on TSAT levels. Transferrin saturation is reported by dividing value of serum iron by total iron binding capacity. | FAS included all participants who were randomized. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Ratio | | Double-Blind Period: Baseline, Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3 | AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and includes both serious & non-serious TEAEs. Severity of AEs was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. | Safety Analysis Set (SAS) includes all participants who had received at least 1 dose of study treatment. Participants were classified according to the treatment received. If a participant was randomized to placebo and received at least 1 dose of mitapivat in the Double-blind Period, then the participant was classified to the mitapivat arm. | Posted | | Count of Participants | | Participants | | Double-Blind Period: From the time of signing informed consent to Week 24 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Plasma Concentration of Mitapivat | | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ (lower limit of quantification). Number analyzed signifies those participants who were evaluable at specified time point. | Posted | | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | | Double-Blind Period: Pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of Mitapivat | Area under the concentration-time curve from time zero to Tlast on dosing day, calculated using the linear-log trapezoidal rule. | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Hours*nanogram per milliliter (h*ng/mL) | | Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Time of Last Quantifiable Concentration (Tlast) of Mitapivat | | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Median | Full Range | hours | | Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Maximum Observed Plasma Concentration (Cmax) of Mitapivat | | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat | | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Median | Full Range | Hours | | Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Last Quantifiable Plasma Concentration (Clast) of Mitapivat | | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set including all subjects with at least 1 mitapivat plasma concentration measurement ≥LLQ. Overall number of participants analyzed indicates number of participants who were evaluable for this outcome measure. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Double-Blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Blood Concentration of Adenosine Triphosphate (ATP) | | Pharmacodynamic (PD) Analysis Set is a subset of the safety analysis set including all participants with at least 1 blood 2,3-DPG or ATP concentration measurement ≥ LLQ. Number analyzed signifies those participants who were evaluable at specified time point. | Posted | | Mean | Standard Deviation | microgram/milliliter (mcg/mL) | | Double-Blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Double-Blind Period: Blood Concentration of 2,3 - Diphosphoglycerate (2,3-DPG) | | Pharmacodynamic (PD) Analysis Set is a subset of the safety analysis set including all participants with at least 1 blood 2,3-DPG or ATP concentration measurement ≥LLQ. Number analyzed signifies those participants who were evaluable at specified time point. | Posted | | Mean | Standard Deviation | mcg/mL | | Double-Blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 20 | | | | ID | Title | Description |
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| OG000 | Mitapivat | Participants randomized to receive Mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks in double blind period and for up to 5 years in open label extension period. | | OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 24 weeks in double blind period followed by Mitapivat 100 mg, orally, BID for up to 5 years in open label extension period. |
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| Secondary | Open-Label Extension Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity of Greater Than or Equal to Grade 3 | AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) is any untoward medical occurrence that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are AEs with an initial onset date during the on-treatment period or worsening from baseline and includes both serious & non-serious TEAEs. Severity of abnormalities was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03): grade 1: mild; grade 2: moderate; grade 3: severe or medically significant but not immediately life-threatening; grade 4: life threatening or disabling; grade 5: death related to AE. | | Not Posted | Dec 2029 | | | | | Open-Label Extension Period: From week 24 up to end of study (approximately 5 years) | | Participants | | | | |