Mitapivat for Sickle Cell Disease

Not currently recruiting at 116 trial locations
AM
Overseen ByAgios Medical Affairs
Age: Any Age
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: Agios Pharmaceuticals, Inc.
Must be taking: Hydroxyurea
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests mitapivat, a medication that may benefit people with sickle cell disease by increasing hemoglobin (the protein in red blood cells that carries oxygen) and reducing painful crises. Participants will join different groups to receive either mitapivat or a placebo to determine which is more effective and safe over time. The trial seeks individuals with sickle cell disease who experience frequent pain crises and are not currently on certain treatments. As a Phase 2 and Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to advance treatment options.

Will I have to stop taking my current medications?

If you're taking hydroxyurea, you can continue as long as your dose is stable for 90 days before starting the study drug. If you're on other treatments for sickle cell disease, like voxelotor or crizanlizumab, you'll need to stop them at least 90 days before joining the trial. Some medications that affect liver enzymes (CYP3A4/5) might also need to be stopped, so discuss this with your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mitapivat is generally safe for people with sickle cell disease. One study found that many patients had better hemoglobin levels when taking mitapivat compared to a placebo, indicating the drug's effectiveness and tolerability. Another study tracked patients for about 2.5 years and found that mitapivat remained safe and beneficial. These benefits included improved hemoglobin levels and other health improvements related to sickle cell disease.

Overall, these studies demonstrate that mitapivat is well-tolerated. Patients did not report any unexpected or severe side effects over the long term, making mitapivat a promising treatment option for sickle cell disease.12345

Why do researchers think this study treatment might be promising for sickle cell disease?

Mitapivat is unique because it targets a different aspect of sickle cell disease compared to standard treatments like hydroxyurea or blood transfusions. Most treatments for sickle cell disease focus on managing symptoms or preventing complications. However, mitapivat works by activating an enzyme called pyruvate kinase-R, which can help improve red blood cell function directly. This novel mechanism offers the potential for a more direct approach in addressing the underlying issues in sickle cell disease, which excites researchers about its potential impact.

What evidence suggests that mitapivat could be an effective treatment for sickle cell disease?

Research has shown that mitapivat can greatly improve hemoglobin levels in people with sickle cell disease. In earlier studies, about 46% of patients taking a 50 mg dose of mitapivat experienced a significant increase in hemoglobin compared to those who took a placebo. This trial may administer either a 50 mg or 100 mg dose of mitapivat, or a mitapivat-matching placebo, to participants. Long-term use of mitapivat has demonstrated lasting benefits, such as reducing anemia and painful sickle cell crises. Over approximately 2.5 years of follow-up, patients continued to experience safety and improvements in blood health. These findings suggest that mitapivat could be a promising option for managing symptoms of sickle cell disease.12356

Are You a Good Fit for This Trial?

Adults and teens aged 16 or older with sickle cell disease (SCD) who've had 2-10 pain crises in the past year can join. They need stable hemoglobin levels between 5.5 and 10.5 g/dL, possibly on a steady dose of hydroxyurea for at least three months, and must use two forms of contraception if they can have children. People with severe liver, gallbladder, kidney diseases, prior gene therapy or transplants, recent other SCD treatments except hydroxyurea, or certain drug interactions are excluded.

Inclusion Criteria

My hydroxyurea dose has been the same for the last 90 days.
I am 16 or older and have completed puberty, or I am 18 or older.
I have been diagnosed with sickle cell disease.
See 3 more

Exclusion Criteria

I am not on strong CYP3A4/5 medications that can't be stopped before starting the study drug.
I do not have significant liver or gallbladder disease.
Pregnant, breastfeeding, or parturient
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Participants receive mitapivat 50 mg or 100 mg BID or placebo for 12 weeks

12 weeks

Phase 3 Treatment

Participants receive mitapivat 100 mg BID or placebo for 52 weeks

52 weeks

Open-label Extension

Participants may opt into receiving mitapivat 50 mg or 100 mg BID for 216 weeks

216 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Mitapivat
  • Mitapivat-matching placebo
Trial Overview The trial is testing Mitapivat against a placebo to see if it raises hemoglobin levels and reduces sickle cell pain crises. Participants will be randomly assigned to receive either Mitapivat or a matching dummy pill (placebo). The study includes an initial phase to set the right dose followed by a longer-term evaluation of its effects.
How Is the Trial Designed?
7Treatment groups
Experimental Treatment
Placebo Group
Group I: Phase 3: Open-Label Extension PeriodExperimental Treatment1 Intervention
Group II: Phase 3: Mitapivat 100 mg BIDExperimental Treatment1 Intervention
Group III: Phase 2: Open-Label Extension PeriodExperimental Treatment1 Intervention
Group IV: Phase 2: Mitapivat 50 mg BIDExperimental Treatment1 Intervention
Group V: Phase 2: Mitapivat 100 mg BIDExperimental Treatment1 Intervention
Group VI: Phase 2: PlaceboPlacebo Group1 Intervention
Group VII: Phase 3: PlaceboPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Agios Pharmaceuticals, Inc.

Lead Sponsor

Trials
55
Recruited
4,200+

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39644907/
Safety and efficacy of mitapivat in sickle cell disease (RISE ...Both treatment groups showed a statistically significant haemoglobin response rate versus placebo (12 [46%] of 26 patients in the mitapivat 50 ...
Long-term mitapivat treatment is safe and efficacious in ...Median of 2.53-year follow-up of mitapivat showed favorable safety and tolerability in patients with SCD. Sustained improvements in Hb, ...
Agios EHA 2025 Data RoomIn the study, mitapivat showed sustained efficacy and tolerability over three years, including improvements in anemia, hemolysis, painful vaso-occlusive crises ...
Long-term mitapivat treatment is safe and efficacious in ...Median of 2.53-year follow-up of mitapivat showed favorable safety and tolerability in patients with SCD. · Sustained improvements in Hb, hemolytic markers, and ...
Agios Completes Enrollment of Phase 3 RISE UP Study ...The RISE UP Phase 2 and 3 studies are evaluating the efficacy and safety of mitapivat in sickle cell disease patients who are 16 years of age ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37934880/
One-year safety and efficacy of mitapivat in sickle cell ...Cellularly, the ATP:2,3-DPG ratio and Hb-oxygen affinity significantly increased and RBC sickling (point of sickling) nonsignificantly reduced.
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