Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000212-34 | EudraCT Number | ||
| 2024-512747-23-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The primary objective of this study was to compare the effect of mitapivat versus placebo on transfusion burden in participants with α- or β-transfusion-dependent thalassemia.
The mitapivat group included 171 participants. The placebo group included 87 participants.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mitapivat | Experimental | Participants randomized to receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 48 weeks in the double-blind (DB) period and for up to 5 years in the open label extension (OLE) period. |
|
| Placebo | Placebo Comparator | Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the DB period followed by mitapivat 100 mg, orally, BID for up to 5 years in the OLE period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Matching Mitapivat | Drug | Tablets |
| |
| Mitapivat |
| Measure | Description | Time Frame |
|---|---|---|
| Double-blind Period: Percentage of Participants Who Achieved Transfusion Reduction Response (TRR) | TRR is defined as ≥50% reduction in transfused red blood cells (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline transfusion burden standardized to 12 weeks. Baseline transfusion burden standardized to 12 weeks= (12/24) × total number of RBC units transfused during 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 12 (Day 85) were considered nonresponders. | Double-blind Period: Baseline through Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Double-blind Period: Percentage of Participants Who Achieved TRR2 | TRR2, defined as a ≥50% reduction in transfused RBC units in any consecutive 24-week period through Week 48 compared with the 24-week baseline transfusion burden, is reported. Baseline transfusion burden standardized to 24 weeks is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 24 (Day 169) were considered nonresponders. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Pregnant, breastfeeding, or parturient;
Documented history of homozygous or heterozygous sickle hemoglobin (Hb S) or hemoglobin C (Hb C);
Prior exposure to gene therapy or prior bone marrow or stem cell transplantation;
Currently receiving treatment with luspatercept; the last dose must have been administered ≥36 weeks before randomization;
Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥36 weeks before randomization;
History of malignancy (active or treated) ≤5 years before providing informed consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;
History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent;
Hepatobiliary disorders;
Estimated glomerular filtration rate <45 milliliters per minute (mL/min)/1.73 meter (m)^2 by Chronic Kidney Disease Epidemiology Collaboration creatinine equation;
Nonfasting triglycerides >440 milligrams per deciliter (mg/dL) (5 millimoles per liter [mmol/L]);
Active infection requiring systemic antimicrobial therapy at the time of providing informed consent;
Positive test for hepatitis C virus antibody (HCVAb) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg);
Positive test for human immunodeficiency virus (HIV)-1 antibody (Ab) or HIV-2 Ab;
History of major surgery (including splenectomy) ≤6 months before providing informed consent and/or a major surgical procedure planned during the study;
Current enrollment or past participation (≤12 weeks before administration of the first dose of study drug or a timeframe equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational treatment or device;
Receiving strong CYP3A4/5 inhibitors that have not been stopped for ≥5 days or a timeframe equivalent to 5 half-lives (whichever is longer); or strong CYP3A4 inducers that have not been stopped for ≥4 weeks or a timeframe equivalent to 5 half-lives (whichever is longer), before randomization;
Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed. The testosterone dose and preparation must be stable for ≥12 weeks before randomization;
Known allergy, or other contraindication, to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate, Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and Federal Food, Drug, and Cosmetic (FD&C) Blue #2]);
Any medical, hematological, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Affairs | Agios Pharmaceuticals, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Phoenix | Arizona | 85016-7710 | United States | ||
| San Diego Hospital, UC San Diego Health |
Not provided
Not provided
Not provided
Not provided
Not provided
A total of 305 participants with a diagnosis of Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-TDT) were screened. Of which, 258 were randomized and 257 received study treatment in this study.
Participants took part at 81 study sites in Malaysia,Taiwan,Thailand,Bulgaria,Brazil,Lebanon,Saudi Arabia,Turkey,United Arab Emirates,Canada, the United States,Denmark,France,Germany,Greece,Italy,Netherlands,Spain and the United Kingdom.Results are reported for 48-week DB period until primary completion date.Analysis of data for OLE period is still ongoing with anticipated completion in June 2029.Results for OLE period will be reported by June 2030.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Mitapivat | Participants randomized to receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 48 weeks in double-blind period. |
| FG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in double-blind period. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 28, 2022 | Apr 11, 2025 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
Tablets |
|
|
| Double-blind period: Baseline through Week 48 |
| Double-blind Period: Percentage of Participants Who Achieved TRR3 | TRR3, defined as a ≥33% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks= (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders. | Double-blind period: Baseline up to Week 13 through Week 48 |
| Double-blind Period: Percentage of Participants Who Achieved TRR4 | TRR4, defined as a ≥50% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks = (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders. | Double-blind period: Baseline up to Week 13 through Week 48 |
| Double-blind Period: Percent Change From Baseline in Transfused RBC Units | Transfusion burden from Week 13 through Week 48 standardized to 36 weeks is defined as number of transfused RBC units from Day 85 through Week 48 in the Double-blind Period ×36/(Number of days from Day 85 through Week 48 in the Double-blind Period/7). Baseline transfusion burden standardized to 36 weeks= (36/24)× is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or within 168 days before the start of study treatment for participants randomized and dosed. | Double-blind Period: Baseline, Week 13 through Week 48 |
| Double-blind Period: Percentage of Participants Who Achieved Transfusion-Independence | Transfusion-independence is defined as transfusion-free for ≥8 consecutive weeks through Week 48 in the double-blind period. | Double-blind Period: Baseline through Week 48 |
| Double-blind Period: Change From Baseline in Iron Levels | Iron metabolism was assessed based on Iron levels. | Double-blind Period: Baseline through Week 48 |
| Double-blind Period: Change From Baseline in Serum Ferritin Levels | Iron metabolism was assessed based on serum ferritin levels. | Double-blind Period: Baseline through Week 48 |
| Double-blind Period: Change From Baseline in Total Iron Binding Capacity | Iron metabolism was assessed based on total iron binding capacity. | Double-blind Period: Baseline through Week 48 |
| Double-blind Period: Change From Baseline in Transferrin Saturation (TSAT) Levels | Iron metabolism was assessed based on TSAT levels. Transferrin saturation is reported by dividing value of serum iron by total iron binding capacity. | Double-blind Period: Baseline through Week 48 |
| 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 | An 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. | Double-blind Period: From first dose of study drug up to week 48 |
| Open-label Extension Period: Number of Participants With TEAEs, Serious TEAEs, Related TEAEs, Related TEAEs and TEAEs With Severity of Greater Than or Equal to 3 | An 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. | Open-Label Extension Period: From Week 48 up to end of study (approximately 5 years) |
| Double-blind Period: Plasma Concentrations of Mitapivat | Double-blind Period: Pre-dose at Week 12; pre-dose at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
| 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. | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
| Double-blind Period: Maximum Observed Plasma Concentration (Cmax) of Mitapivat | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 |
| Double-blind Period: Time to Reach of Maximum Observed Plasma Concentration (Tmax) of Mitapivat | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 |
| Double-blind Period: Time of Last Quantifiable Concentration (Tlast) of Mitapivat | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 |
| Double-blind Period: Last Quantifiable Plasma Concentration (Clast) of Mitapivat | Clast is the last quantifiable concentration after a single dose or within the dosing interval (tau) for multiple doses. | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 |
| Double-blind Period: Blood Concentration of Adenosine Triphosphate (ATP) | Double-blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
| Double-blind Period: Blood Concentration of 2,3 - Diphosphoglycerate (2,3-DPG) | Double-blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
| La Jolla |
| California |
| 92093 |
| United States |
| Children's Hospital Oakland | Oakland | California | 94609-1809 | United States |
| Stanford Medicine | Palo Alto | California | 94304-1601 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201-2196 | United States |
| Weill Cornell Medical Center | New York | New York | 10065-4870 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710-3038 | United States |
| Penn Medicine - University of Pennsylvania Health System | Philadelphia | Pennsylvania | 19104 | United States |
| Seattle Cancer Care Alliance, University of Washington | Seattle | Washington | 98101 | United States |
| Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP | Ribeirão Preto | 14051-260 | Brazil |
| GSH Banco de Sangue de São Paulo | São Paulo | 04006-002 | Brazil |
| MHAT "Dr. Nikola Vasiliev" AD | Kyustendil | 2500 | Bulgaria |
| UMHAT "Dr. Georgi Stranski" Pleven | Pleven | 5800 | Bulgaria |
| UMHAT "Sveti Georgi" EAD | Plovdiv | 4002 | Bulgaria |
| SHATHD Sofia | Sofia | 1756 | Bulgaria |
| UMHAT "Prof. Dr. Stoyan Kirkovich" | Stara Zagora | 6000 | Bulgaria |
| Foothills Medical Centre | Calgary | Alberta | T2N 2T9 | Canada |
| Toronto General Hospital, University Health Network | Toronto | Ontario | M5G 2C4 | Canada |
| Rigshospitalet | Hovedstaden | 2100 | Denmark |
| CHU Hôpital Henri Mondor | Créteil | 94010 | France |
| Hôpital Edouard Herriot, CHU de Lyon | Lyon | 69003 | France |
| CHU Hôpital de la Timone | Marseille | 13385 | France |
| Hôpital Necker Enfants Malades | Paris | 75015 | France |
| Charité - UB - CVK - Medizinische Klinik | Berlin | 13353 | Germany |
| Universitätsklinikum Essen | Essen | 45122 | Germany |
| Universitätsklinikum Leipzig | Leipzig | 04103 | Germany |
| University General Hospital of Patras | Achaia | 26504 | Greece |
| Laiko General Hospital | Athens | 115 26 | Greece |
| Children's Hospital Agia Sophia, National and Kapodistrian University of Athens Medical School | Athens | 11527 | Greece |
| University Hospital of Ioannina | Ioannina | 455 00 | Greece |
| Ippokrateio General Hospital | Thessaloniki | 546 42 | Greece |
| Ospedale "A. Perrino" - Brindisi | Brindisi | 72100 | Italy |
| Ospedale Pediatrico Microcitemico | Cagliari | 09121 | Italy |
| Ospedale Sant'Anna | Ferrara | 44124 | Italy |
| Ente Ospedaliero Ospedali Galliera | Genova | 16128 | Italy |
| Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milan | 20122 | Italy |
| A.O.U Di Modena | Modena | 41124 | Italy |
| AOU L. Vanvitelli Universita degli Studi della Campania Luigi Vanvitelli | Naples | 80138 | Italy |
| A.O.U. San Luigi Gonzaga | Orbassano | 10043 | Italy |
| Chronic Care Center | Beirut | 9999 | Lebanon |
| Hospital Sultanah Bahiyah | Alor Star | 05460 | Malaysia |
| Hospital Sultanah Aminah Johor Bahru | Johor Bahru | 80100 | Malaysia |
| Hospital Queen Elizabeth, Kota Kinabalu | Kota Kinabalu | 88586 | Malaysia |
| Hospital Tunku Azizah | Kuala Lumpur | 50300 | Malaysia |
| Hospital Tengku Ampuan Afzan | Kuantan | 25100 | Malaysia |
| Hospital Umum Sarawak | Kuching | 93586 | Malaysia |
| Hospital Ampang | Pandan Indah | 68000 | Malaysia |
| Hospital Pulau Pinang | Pulau Pinang | 10990 | Malaysia |
| Amsterdam Universitair Medisch Centrum, Locatie AMC | Amsterdam | 1105 AZ | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584 CX | Netherlands |
| Erasmus MC | Westzeedijk 353 | 3015 AA | Netherlands |
| King Abdullah International Medical Research Center | Riyadh | 14611 | Saudi Arabia |
| King Khalid University Hospital | Riyadh | 90210 | Saudi Arabia |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Universitario Virgen Arrixaca | Murcia | 30120 | Spain |
| Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Phramongkutklao Hospital | Bangkok | 10400 | Thailand |
| Ramathibodi Hospital | Bangkok | 10400 | Thailand |
| Faculty of Medicine Siriraj Hospital | Bangkok | 10700 | Thailand |
| Maharaj Nakorn Chiang Mai Hospital | Chiang Mai | 50200 | Thailand |
| Srinagarind Hospital, Khon Kaen University | Khon Kaen | 40000 | Thailand |
| Naresuan University Hospital | Mueang Phitsanulok | 65000 | Thailand |
| King Chulalongkorn Memorial Hospital | Pathum Wan | Thailand |
| Acibadem Adana Hospital | Adana | 1130 | Turkey (Türkiye) |
| Akdeniz University Faculty of Medicine | Antalya | 07059 | Turkey (Türkiye) |
| Çukurova University | Balcalı | 01330 | Turkey (Türkiye) |
| Ege University Faculty of Medicine | Bornova | 35040 | Turkey (Türkiye) |
| Istanbul University Faculty of Medicine | Fatih | 34093 | Turkey (Türkiye) |
| Hacettepe University | Mersin | Turkey (Türkiye) |
| Burjeel Medical City | Abu Dhabi | United Arab Emirates |
| Imperial College Healthcare NHS Trust - Hammersmith Hospital | London | W12 0HS | United Kingdom |
| University College London | London | WC1E 6BT | United Kingdom |
| Safety Analysis Set | Safety Analysis Set: all participants who received at least 1 dose of study treatment. If a participant randomized to placebo received at least 1 dose of mitapivat in the double-blind period, then the participant is classified to the mitapivat arm. One participant, randomized to placebo, received mitapivat and was classified in the mitapivat arm in the safety analysis set. |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Full analysis set (FAS) included all participants who were randomized.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Mitapivat | Participants randomized to receive mitapivat 100 mg, orally, BID for 48 weeks in double-blind period. |
| BG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in double-blind period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Double-blind Period: Percentage of Participants Who Achieved Transfusion Reduction Response (TRR) | TRR is defined as ≥50% reduction in transfused red blood cells (RBC) units with a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline transfusion burden standardized to 12 weeks. Baseline transfusion burden standardized to 12 weeks= (12/24) × total number of RBC units transfused during 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 12 (Day 85) were considered nonresponders. | FAS included all participants who were randomized. | Posted | Number | percentage of participants | Double-blind Period: Baseline through Week 48 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Percentage of Participants Who Achieved TRR2 | TRR2, defined as a ≥50% reduction in transfused RBC units in any consecutive 24-week period through Week 48 compared with the 24-week baseline transfusion burden, is reported. Baseline transfusion burden standardized to 24 weeks is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 24 (Day 169) were considered nonresponders. | FAS included all participants who were randomized. | Posted | Number | percentage of participants | Double-blind period: Baseline through Week 48 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Percentage of Participants Who Achieved TRR3 | TRR3, defined as a ≥33% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks= (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders. | FAS included all participants who were randomized. | Posted | Number | percentage of participants | Double-blind period: Baseline up to Week 13 through Week 48 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Percentage of Participants Who Achieved TRR4 | TRR4, defined as a ≥50% reduction in transfused RBC units from Week 13 through Week 48 compared with the baseline transfusion burden standardized to 36 weeks, is reported. Baseline transfusion burden standardized to 36 weeks = (36/24) × total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or the start of study treatment for participants randomized and dosed. Participants withdrawn from the study before Week 48 were considered nonresponders. | FAS included all participants who were randomized. | Posted | Number | percentage of participants | Double-blind period: Baseline up to Week 13 through Week 48 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Percent Change From Baseline in Transfused RBC Units | Transfusion burden from Week 13 through Week 48 standardized to 36 weeks is defined as number of transfused RBC units from Day 85 through Week 48 in the Double-blind Period ×36/(Number of days from Day 85 through Week 48 in the Double-blind Period/7). Baseline transfusion burden standardized to 36 weeks= (36/24)× is the total number of RBC units transfused during the 24-week period before the randomization date for participants randomized and not dosed or within 168 days before the start of study treatment for participants 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 | percent change | Double-blind Period: Baseline, Week 13 through Week 48 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Percentage of Participants Who Achieved Transfusion-Independence | Transfusion-independence is defined as transfusion-free for ≥8 consecutive weeks through Week 48 in the double-blind period. | FAS included all participants who were randomized. | Posted | Number | percentage of participants | Double-blind Period: Baseline through Week 48 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Change From Baseline in Iron Levels | Iron metabolism was assessed based on Iron 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 | micromoles per liter (µmol/L) | Double-blind Period: Baseline through Week 48 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Change From Baseline in Serum Ferritin Levels | 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 | micrograms per liter (µg/L) | Double-blind Period: Baseline through Week 48 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Change From Baseline in Total Iron Binding Capacity | Iron metabolism was assessed based on 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 | µmol/L | Double-blind Period: Baseline through Week 48 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Change From Baseline in Transferrin Saturation (TSAT) Levels | 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 through Week 48 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | An 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) included 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. One subject, randomized to placebo, received mitapivat and was classified in the mitapivat arm in the safety analysis set. | Posted | Count of Participants | Participants | Double-blind Period: From first dose of study drug up to week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Open-label Extension Period: Number of Participants With TEAEs, Serious TEAEs, Related TEAEs, Related TEAEs and TEAEs With Severity of Greater Than or Equal to 3 | An 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 | Jun 2030 | Open-Label Extension Period: From Week 48 up to end of study (approximately 5 years) | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Plasma Concentrations of Mitapivat | Pharmacokinetic (PK) Analysis Set included a subset of the safety analysis set and included all participants with at least 1 mitapivat plasma concentration measurement ≥ lower limit of quantification (LLQ). 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 at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | PK analysis set is a subset of the safety analysis set and included all participants with at least 1 plasma mitapivat 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*nanograms per milliliter (h*ng/mL) | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Maximum Observed Plasma Concentration (Cmax) of Mitapivat | PK analysis set is a subset of the safety analysis set and included all participants with at least 1 plasma mitapivat 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 | nanograms per milliliter (ng/mL) | Double-blind Period: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 36 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Time to Reach of Maximum Observed Plasma Concentration (Tmax) of Mitapivat | PK analysis set is a subset of the safety analysis set and included all participants with at least 1 plasma mitapivat 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 Week 36 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Time of Last Quantifiable Concentration (Tlast) of Mitapivat | PK analysis set is a subset of the safety analysis set and included all participants with at least 1 plasma mitapivat 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 Week 36 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Last Quantifiable Plasma Concentration (Clast) of Mitapivat | Clast is the last quantifiable concentration after a single dose or within the dosing interval (tau) for multiple doses. | PK analysis set is a subset of the safety analysis set and included all participants with at least 1 plasma mitapivat 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 Week 36 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Blood Concentration of Adenosine Triphosphate (ATP) | Pharmacodynamic (PD) analysis set is a subset of the safety analysis set and included all participants with at least 1 blood 2,3-diphosphoglycerate (DPG) or ATP concentration measurement ≥ LLQ. Number analyzed signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | µg/mL | Double-blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Double-blind Period: Blood Concentration of 2,3 - Diphosphoglycerate (2,3-DPG) | PD analysis set is a subset of the safety analysis set and included all participants with at least 1 blood 2,3-diphosphoglycerate (2,3-DPG) or adenosine triphosphate (ATP) concentration measurement ≥LLQ. Number analyzed signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | µg/mL | Double-blind Period: Pre-dose at Day 1; pre-dose at Week 12; pre-dose at Week 24; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose at Week 36 |
|
|
Double-blind period: From first dose of study drug up to week 48
AEs: Safety Analysis Set (SAS) was used. One participant, randomized to placebo, received mitapivat and is classified in the mitapivat arm in the SAS. All-Cause Mortality: FAS was used. Safety data are presented for Double-blind Period only. The OLE period is ongoing with anticipated completion in June 2029. Results for OLE will be reported separately by June 2030.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Mitapivat | Participants randomized to receive mitapivat 100 mg, orally, BID for 48 weeks in the double-blind period. | 0 | 171 | 19 | 172 | 122 | 172 |
| EG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the double-blind period. | 0 | 87 | 13 | 85 | 50 | 85 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Splenic haematoma | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Hypersplenism | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Mesenteric lymphadenitis | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Dengue fever | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cholangitis acute | Hepatobiliary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Arrhythmia supraventricular | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Hepatic cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 27.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Renal mass | Renal and urinary disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Ovarian cyst ruptured | Reproductive system and breast disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 27.0 | Systematic Assessment |
| |
| Limb deformity | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 27.0 | Systematic Assessment |
| |
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 27.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Initial insomnia | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Middle insomnia | Psychiatric disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 27.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 27.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Agios Medical Affairs | Agios Pharmaceuticals, Inc. | 833-228-8474 | medinfo@agios.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 14, 2022 | Apr 11, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C000634504 | mitapivat |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Black or African American |
|
| American Indian or Alaska Native |
|
| Native Hawaiian or Other Pacific Islander |
|
| Multiracial |
|
| Unknown |
|
| Not reported |
|
|
|
|
|
|
|
| Counts |
|---|
| Participants |
|
|
|
|
|
|
|
Participants randomized to receive mitapivat 100 mg, orally, BID for 48 weeks in the double-blind period.
| OG001 | Placebo | Participants randomized to receive placebo matching mitapivat, orally, BID for 48 weeks in the double-blind period. |
|
|
|
|
|
|
|
|
|
|