Sickle Cell Disease MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Mitapivat
Product Code: AG-348
Pharmaceutical Form: Tablet
INN or Proposed INN: Mitapivat
CAS Number: 2151847-10-6
Current Sponsor code: AG-348 sulfate hydrate
Other descriptive name: AG
Sponsors
Agios Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age =16 years; subjects age 16 or 17 years must physically have completed puberty. • Documented diagnosis of SCD (HbSS, HbSC, HbS/ß0-thalassemia, HbS/ß+ thalassemia, or other sickle cell syndrome variants). • At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months. • Hemoglobin =5.5 and =10.5 g/dL. • If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug. • Women capable of becoming pregnant and men with partners who are women that are capable of becoming pregnant must agree to use 2 forms of contraception. • Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? yes Number of subjects for this age range: 26 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: • Pregnant or breastfeeding. • Receiving regularly scheduled transfusions. • Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease. • Severe kidney disease. • Prior exposure to gene therapy or prior bone marrow or stem cell transplantation. • Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of such therapies must have been administered at least 90 days before starting study drug. • Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug. • Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial. • Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor). • Other protocol defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 2) To determine the recommended Phase 3 dose of mitapivat by evaluating the effect of 2 dose levels of mitapivat versus placebo on: • Anemia in subjects with sickle cell disease (SCD) • Safety Phase 3) To determine the effect of mitapivat versus placebo on: • Anemia in subjects with sickle cell disease (SCD) • Sickle cell pain crises (SCPCs) in subjects with SCD;Secondary Objective: Phase 2) To evaluate the effect of 2 doses of mitapivat versus placebo on: - Anemia - Markers of hemolysis and erythropoiesis - Patient-reported fatigue - Sickle cell pain crises (SCPCs). To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat. Phase 3) To evaluate the effect of mitapivat versus placebo on: • Anemia in subjects with SCD • Markers of hemolysis • Markers of erythropoiesis • Patient-reported fatigue • Additional clinical efficacy measures related to SCPC;Primary end point(s): Phase 2 Primary Endpoints: • Percentage of participants with hemoglobin (Hb) response • Percentage of participants with treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs) Phase 3 Primary Endpoints • Percentage of participants with hemoglobin (Hb) response • Annualized rate of Sickle Cell Pain Crises (SCPCs);Timepoint(s) of evaluation of this end point: Phase 2 primary endpoint of percentage of participants with Hb response: Week 12 Phase 2 primary endpoint of percentage of participants with treatment emergent AEs and treatment emergent SAEs: Up to Week 12 Phase 3 primary endpoint of percentage of participants with Hb response: Week 52 Phase 3 primary endpoint of annualized rate of sickle cell pain crises: Up to Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Phase 2 Endpoints #1,2,3,4,5,6,7: Baseline, Week 10 up to Week 12 Endpoint #8: Up to Week 12 Endpoints #9,10,11,12: Day 1 up to Week 8 Phase 3 Endpoints #1,2,3,4,6,7,8: Baseline, Week 24 up to Week 52 Endpoint #5,11,12,13,14: Up to Week 52 Endpoints #9,10: Baseline, Weeks 24, 28, 40, and 52 Endpoints #15,18,19: Baseline, Week 52 Endpoints #16,17: Baseline, Week 24 and 52 Endpoint #20: Up to 56 weeks Endpoints #21,22,23,24: Day 1 up to Week 40;Secondary end point(s): Phase 2 Secondary Endpoints 1. Change from baseline in Hb concentration 2. Change from baseline in indirect bilirubin 3. Change from baseline in lactate dehydrogenase (LDH) 4. Change from baseline in absolute reticulocyte count 5. Change from baseline in percent reticulocytes 6. Change from baseline in erythropoietin 7. Change from baseline in Patient-Reported Outcomes Measurement Information System® (PROMIS®) Fatigue 13a Short Form (SF) Score 8. Annualized Rate of SCPCs 9. Pharmacokinetic/Pharmacodynamic Relationship: Evaluate the Exposure of Mitapivat to the Change in Adenosine Triphosphate (ATP) and 2,3-Diphosphoglycerate (2,3-DPG) 10. Mitapivat Concentration Over Time 11. Mitapivat Area Under the Concentration-time curve 12. Mitapivat Maximum (Peak) Concentration Phase 3 Secondary Endpoints 1. Change From Baseline in Hb Concentration 2. Change From Baseline in Indirect Bilirubin 3. Change From Baseline in Percent Reticulocytes 4. Change From Baseline in PROMIS® Fatigue 13a SF Scores 5. Annualized Frequency of Hospitalizations for SCPC 6. Change From Baseline in LDH Concentration 7. Change From Baseline in Absolute Reticulocytes 8. Change From Baseline in Erythropoietin 9. Percentage of Participants With Improvement in the Patient Global Impression of Severity (PGIS) -Fatigue 10. Percentage of Participants With Improvement in the Patient Global Impression of Change (PGIC) -Fatigue 11. Time to First SCPC 12. Time to Second SCPC 13. Annuali | — |
Countries
Belgium, Brazil, Canada, Egypt, France, Germany, Israel, Italy, Kenya, Lebanon, Netherlands, Nigeria, Oman, Saudi Arabia, Turkey, United Kingdom, United States
Contacts
Public ContactDirector, Scientific Communications
Agios Pharmaceuticals, Inc.
Outcome results
None listed