A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT) (ENERGIZE)
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| ClinicalTrials.gov Identifier: NCT04770753 |
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Recruitment Status :
Recruiting
First Posted : February 25, 2021
Last Update Posted : February 13, 2023
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Sponsor:
Agios Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.
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Brief Summary:
The primary purpose of this study is to compare the effect of mitapivat versus placebo on anemia in participants with alpha- or beta-non-transfusion dependent thalassemia (NTDT).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-Transfusion-dependent Alpha-Thalassemia Non-Transfusion-dependent Beta-Thalassemia | Drug: Placebo Matching Mitapivat Drug: Mitapivat | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 171 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Mitapivat in Subjects With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (ENERGIZE) |
| Actual Study Start Date : | November 8, 2021 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2028 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Thalassemia
Drug Information available for:
Mitapivat
| Arm | Intervention/treatment |
|---|---|
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Experimental: Mitapivat
Double-blind Period: Participants will receive mitapivat 100 milligrams (mg), orally, twice daily (BID) for 24 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to continue to receive mitapivat for up to an additional 5 years after the Double-blind Period. |
Drug: Mitapivat
Tablets
Other Names:
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Placebo Comparator: Placebo
Double-blind Period: Participants will receive placebo matching mitapivat, orally, BID for 24 weeks. Open-label Extension Period: Participants who do not discontinue study drug may choose to receive mitapivat for up to an additional 5 years after the Double-blind Period. |
Drug: Placebo Matching Mitapivat
Tablets Drug: Mitapivat Tablets
Other Names:
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Primary Outcome Measures :
- Percentage of Participants With Hemoglobin (Hb) Response [ Time Frame: Baseline, Week 12 up to Week 24 ]Hb response is defined as a ≥1.0 gram per deciliter (g/dL) increase in average Hb concentration from Week 12 through Week 24 compared with baseline.
Secondary Outcome Measures :
- Change From Baseline in Average Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue Subscale Score from Week 12 through Week 24 [ Time Frame: Baseline, Week 12 up to Week 24 ]The 13-item FACIT-Fatigue subscale assesses severity and impact of fatigue. The subscale has a 7-day recall period, and total score ranges from 0 to 52, with a higher score indicating less fatigue.
- Change From Baseline in Average Hb Concentration From Week 12 through Week 24 [ Time Frame: Baseline, Week 12 up to Week 24 ]
- Percentage of Participants With Hb 1.5+ Response [ Time Frame: Baseline, Week 12 up to Week 24 ]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.
- Change From Baseline in Indirect Bilirubin at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Haptoglobin at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Reticulocytes at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Erythropoietin at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percentage of Participants With Improvement in the Patient Global Impression of Severity (PGIS) -Fatigue by at Least 1 Category at Weeks 12, 16, 20, and 24 Compared With Baseline, or "No Change" if No or Mild Fatigue at Baseline [ Time Frame: Baseline, Weeks 12, 16, 20, and 24 ]The PGIS-Fatigue assesses severity of fatigue (on a 4-point scale ranging from "None" to "Severe") over a 7-day recall period. Improvement in the PGIS-Fatigue by at least one category or no change if "None" or "Mild" PGIS-Fatigue response at baseline will be assessed separately at Weeks 12, 16, 20, and 24 compared to baseline.
- Percentage of Participants With Improvement in the Patient Global Impression of Change (PGIC) -Fatigue at Weeks 12, 16, 20, and 24, or "No Change" if No or Mild Fatigue at Baseline [ Time Frame: Weeks 12, 16, 20, and 24 ]The PGIC-Fatigue assesses change in fatigue compared with baseline (on a 5-point scale ranging from "Much better" to "Much worse"). Participants reporting improvement in the PGIC-Fatigue or reporting "No change" if "None" or "Mild" PGIS-Fatigue response at baseline will be assessed separately at Weeks 12, 16, 20, and 24.
- Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Serum Ferritin at Week 24 [ Time Frame: Baseline, Week 24 ]
- Change From Baseline in Transferrin Saturation (TSAT) at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 293 ]
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), Graded by Severity [ Time Frame: Up to Week 293 ]AEs and SAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; Version 4.03) from Grades 1 to 4 where Grade 1 is mild and Grade 4 is life-threatening.
- Percentage of Participants With Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug [ Time Frame: Up to Week 293 ]
- Percentage of Participants With Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug [ Time Frame: Up to Week 293 ]
- Plasma or Blood Concentrations Over Time for Mitapivat [ Time Frame: Pre-dose Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
- Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
- Maximum Plasma Concentration (Cmax) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
- Time of Maximum Plasma Concentration (Tmax) of Mitapivat [ Time Frame: Pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
- Blood Concentration of Adenosine Triphosphate (ATP) [ Time Frame: Pre-dose Day 1; pre-dose Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
- Blood Concentration of 2,3 - diphosphoglycerate (2,3-DPG) [ Time Frame: Pre-dose Day 1; pre-dose Week 12; pre-dose, 0.5, 1, 3, 5, 7 hours post-dose Week 20 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Documented diagnosis of thalassemia (β-thalassemia with or without α-globin gene mutations, hemoglobin E (HbE)/β-thalassemia, or α-thalassemia/hemoglobin H [HbH] disease) based on Hb electrophoresis, Hb high-performance liquid chromatography (HPLC)), and/or deoxyribonucleic acid (DNA) analysis;
- Hb concentration ≤10.0 grams per deciliter (g/dL) (100.0 grams per liter [g/L]), based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period;
- Non-transfusion-dependent, defined as ≤5 red blood cell (RBC) units during the 24-week period before randomization; and no RBC transfusions ≤8 weeks before providing informed consent and no RBC transfusions during the Screening Period;
- If taking hydroxyurea, the hydroxyurea dose must be stable for ≥16 weeks before randomization;
- Women of child-bearing potential (WOCBP) must be abstinent of sexual activities that may result in pregnancy as part of their usual lifestyle or agree to use 2 forms of contraception, one of which must be considered highly effective, from the time of providing informed consent, throughout the study, and for 28 days after the last dose of study drug. The second form of contraception can be an acceptable barrier method;
- Written informed consent before any study-related procedures are conducted and willing to comply with all study procedures for the duration of the study.
Exclusion Criteria:
- Pregnant, breastfeeding, or parturient
- Documented history of homozygous or heterozygous sickle hemoglobin (HbS) or hemoglobin C (HbC);
- 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 ≥18 weeks before randomization;
- Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered ≥18 weeks before randomization;
- History of malignancy, (active or treated) ≤5 years before providing informed consent;
- History of active and/or uncontrolled cardiac or pulmonary disease ≤6 months before providing informed consent, except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ;
- Hepatobiliary disorders;
- Estimated glomerular filtration rate <45 milliliters per minute (mL/min)/1.73 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) ≤16 weeks 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 ≥10 weeks before randomization;
- Known allergy 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 FD&C Blue #2]);
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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:
- Participants who are institutionalized by regulatory or court order
- Participants with any condition(s) that could create undue influence (including but not limited to incarceration, involuntary psychiatric confinement, and financial or familial affiliation with the Investigator or Sponsor)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04770753
Contacts
| Contact: Medical Affairs | 833-228-8474 | medinfo@agios.com |
Locations
Show 85 study locations
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
| Study Chair: | Medical Affairs | Agios Pharmaceuticals, Inc. |
| Responsible Party: | Agios Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT04770753 |
| Other Study ID Numbers: |
AG348-C-017 2021-000211-23 ( EudraCT Number ) |
| First Posted: | February 25, 2021 Key Record Dates |
| Last Update Posted: | February 13, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Thalassemia beta-Thalassemia alpha-Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic |
Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |