Mitapivat for Anemia

(SATISFY-CA Trial)

Overseen By Kevin Kuo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Folic acid

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pyruvate kinase deficiency, Hypertension, Heart failure, Diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new drug, mitapivat, for individuals with certain types of anemia, specifically RBC membranopathies and congenital dyserythropoietic anemia type II (CDAII). These conditions affect red blood cells, causing symptoms such as fatigue and possibly an enlarged spleen. Participants will take mitapivat over several weeks to determine if it improves their condition. This trial suits those diagnosed with these specific types of anemia who experience symptoms like fatigue due to red blood cell breakdown. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, such as strong inhibitors or inducers of CYP3A4, at least 5 days before starting the study treatment. Additionally, if you are on hematopoietic stimulating agents, you must stop them at least 28 days before the trial begins. You must also continue taking at least 0.8 mg of folic acid daily during the study.

Is there any evidence suggesting that mitapivat is likely to be safe for humans?

Research has shown that mitapivat is generally safe. In studies involving 155 participants taking mitapivat, most continued the treatment for over 24 weeks without major issues. Although some serious side effects, such as hemolytic anemia and sore throat, did occur, they were rare and affected only a few patients. Overall, mitapivat is considered relatively safe, and previous patients found it promising for treating anemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anemia?

Mitapivat is unique because it targets the root cause of certain types of anemia by activating an enzyme called pyruvate kinase. Unlike standard treatments like blood transfusions or erythropoiesis-stimulating agents, which mainly address symptoms, Mitapivat works at the cellular level to improve red blood cell function. Researchers are particularly excited about Mitapivat because it offers a new mechanism of action that could lead to more sustainable and long-term improvements in blood health for patients with anemia.

What evidence suggests that mitapivat might be an effective treatment for anemia?

Research has shown that mitapivat, the treatment under study in this trial, can improve anemia by increasing hemoglobin levels, which are crucial for oxygen transport in the blood. Studies have found that patients treated with mitapivat experienced better hemoglobin levels, leading to improved anemia symptoms. In patients with conditions like pyruvate kinase deficiency, mitapivat not only raised hemoglobin levels but also reduced red blood cell breakdown. These findings suggest that mitapivat could effectively treat rare types of anemia, such as CDAII, by enhancing the health and function of red blood cells. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with rare anemia types, specifically RBC membranopathies or CDAII. It's open to about 9 individuals from Princess Margaret who will undergo treatment and follow-up for a total of 58 weeks.

Inclusion Criteria

I am taking or will start taking daily folic acid as required.

Average hemoglobin (Hb) concentration must be less than 13.0 g/dL for males and 11.0 g/dL for females. Patients with average Hb >10.0 g/dL for males and females must meet additional criteria such as splenomegaly, fatigue attributed to hemolysis, or active hemolysis

Be willing and able to give written informed consent and to comply with all study procedures for the duration of the study

Exclusion Criteria

Positive test for HIV-1 or -2 antibodies

Current or recent history of psychiatric disorder that could compromise the ability to cooperate with study visits and procedures

Alcohol use disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

≤50 days

Dose Escalation

Participants receive an initial dose of 50 mg mitapivat BID, increased to 100 mg BID after 4 weeks unless dose limiting side effects occur

8 weeks

Regular visits for dose adjustment and monitoring

Fixed Dose Period 1

Participants receive a fixed dose of mitapivat

24 weeks

Regular visits for monitoring

Fixed Dose Period 2

Continuation of fixed dose of mitapivat

24 weeks

Regular visits for monitoring

Dose Taper

Participants undergo dose tapering

1 week

Final visit for dose tapering

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mitapivat

Trial Overview The study tests Mitapivat's safety and effectiveness in treating certain anemias. Participants will have an initial dose escalation period of 8 weeks, followed by a fixed dose for 48 weeks, and finally a tapering week.

How Is the Trial Designed?

Group I: Mitapivat Experimental Treatment 1 Intervention

All patients will receive the drug Mitapivat

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Agios Pharmaceuticals, Inc.

Industry Sponsor

Trials

55

Recruited

4,200+

Citations

1. ashpublications.org ashpublications.org/ashclinicalnews/news/8478/Study-Confirms-Safety-Efficacy-of-Mitapivat-to

Study Confirms Safety, Efficacy of Mitapivat to Improve Anemia ... Mitapivat was efficacious in improving anemia; significantly higher rates of hemoglobin response were observed in patients who received 50 mg ...

2. pubmed.ncbi.nlm.nih.gov pubmed.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 ...

3. investor.agios.com investor.agios.com/news-releases/news-release-details/agios-presents-positive-results-phase-3-energize-t-study

Agios Presents Positive Results from Phase 3 ENERGIZE ... The results demonstrated that mitapivat improves hemolytic anemia and quality-of-life related measures, as measured by significant reductions ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2116634

Mitapivat versus Placebo for Pyruvate Kinase Deficiency In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050598425000149

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 ...

6. pyrukynd.com pyrukynd.com/hcp/pyrukynd-safety/

Safety Profile | PYRUKYND® (mitapivat) tablets PYRUKYND® (mitapivat) demonstrated safety profile. 1​​ Among 155 who received PYRUKYND in clinical trials, 79% were exposed for longer than 24 weeks.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1902678

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/216196s000lbl.pdf

PYRUKYND® (mitapivat) tablets, for oral use Untreated PK deficiency in pregnant women may precipitate acute hemolysis, pre-term labor, miscarriage and severe anemia requiring frequent transfusion.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31483964/

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency The most common serious adverse events, hemolytic anemia and pharyngitis, each occurred in 2 patients (4%). A total of 26 patients (50%) had an ...