Purpose

This clinical trial is a Phase 2/3 study that will determine the recommended dose of mitapivat and evaluate the efficacy and safety of mitapivat in sickle cell disease by testing how well mitapivat works compared to placebo to increase the amount of hemoglobin in the blood and to reduce or prevent the occurrence of sickle cell pain crises. In addition, the long-term effect of mitapivat on efficacy and safety will be explored in an open-label extension portion.

Condition

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age 16 years or older (18 years or older [France and Germany]); participants age 16 or 17 years must physically have completed puberty; - Documented diagnosis of sickle cell disease (SCD) (HbSS, HbSC [combined heterozygosity for hemoglobins S and C], HbS/beta 0- thalassemia, HbS/ beta plus 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 at least 5.5 and 10.5 gram per deciliter (g/dL) at the most. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period; - 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.

Exclusion Criteria

  • Pregnant, breastfeeding, or parturient; - 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).

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 2: Mitapivat 50 mg BID
Double-blind Period: Mitapivat 50 milligrams (mg) twice daily (BID) for 12 weeks.
  • Drug: Mitapivat
    Mitapivat tablets
    Other names:
    • AG-348
    • Mitapivat Sulfate
Experimental
Phase 2: Mitapivat 100 mg BID
Double-blind Period: Mitapivat 100 mg BID for 12 weeks.
  • Drug: Mitapivat
    Mitapivat tablets
    Other names:
    • AG-348
    • Mitapivat Sulfate
Placebo Comparator
Phase 2: Placebo
Double-blind Period: Mitapivat-matching placebo for 12 weeks.
  • Other: Mitapivat-matching placebo
    Placebo to match 50 mg or 100 mg tablets
Experimental
Phase 2: Open-Label Extension Period
Participants who received mitapivat 50mg BID in the double-blind period may choose to receive mitapivat 50mg BID for 216 weeks after. Participants who received mitapivat 100mg BID in the double-blind period may choose to receive mitapivat 100 mg BID for 216 weeks after. Participants who received mitapivat-matching placebo in the double-blind period, may be randomized to receive either mitapivat 50 mg or 100 mg BID for 216 weeks after.
  • Drug: Mitapivat
    Mitapivat tablets
    Other names:
    • AG-348
    • Mitapivat Sulfate
Experimental
Phase 3: Mitapivat selected Phase 3 dose
Double-blind Period: Mitapivat selected Phase 3 dose (50 mg or 100 mg BID) for 52 weeks.
  • Drug: Mitapivat
    Mitapivat tablets
    Other names:
    • AG-348
    • Mitapivat Sulfate
Placebo Comparator
Phase 3: Placebo
Double-blind Period: Mitapivat-matching placebo selected Phase 3 dose (which can be either 50 mg or 100 mg BID based on the phase 2 results) for 52 weeks.
  • Other: Mitapivat-matching placebo
    Placebo to match selected Phase 3 dose tablets
Experimental
Phase 3: Open-Label Extension Period
Participants may choose to receive the selected Phase 3 mitapivat dose (which can be either 50 mg or 100 mg BID based on the phase 2 results) for 216 weeks after the Double-blind Period.
  • Drug: Mitapivat
    Mitapivat tablets
    Other names:
    • AG-348
    • Mitapivat Sulfate

Recruiting Locations

Boston Medical Center & Boston University School of Medicine
Boston, Massachusetts 02118

More Details

Status
Recruiting
Sponsor
Agios Pharmaceuticals, Inc.

Study Contact

Agios Medical Affairs
833-228-8474
medinfo@agios.com

Detailed Description

Mitapivat is a small molecule, oral activator of pyruvate kinase R (PKR). PKR is involved with maintaining health, energy, and longevity of red blood cells (RBCs). The study aims to evaluate the efficacy and safety of treatment with mitapivat in participants with sickle cell disease. The study is a Phase 2/3 study in which the recommended dose of mitapivat will be selected and further evaluated. The Phase 2 portion includes a 12-week randomized, placebo-controlled period in which participants will be randomized in a 1:1:1 ratio to receive 2 dose levels of mitapivat or placebo. The Phase 3 portion includes a 52-week randomized, placebo-controlled period in which participants will be randomized in a 2:1 ratio to receive the recommended mitapivat dose level or placebo. Participants who complete either the Phase 2 or Phase 3 portion will have the option to move into a 216-week open label extension period to receive mitapivat.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.