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Allosteric Activator

Long-Term Mitapivat for Sickle Cell Disease

Phase 1 & 2

Waitlist Available

Led By Julia Z Xu, M.D.

Research Sponsored by National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

1.6 For women of reproductive potential, have a negative serum pregnancy test during the screening period. Women of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not been naturally postmenopausal (i.e., who have not menstruated at all for at least the preceding 1 year prior to signing informed consent unrelated to hormonal contraception).

f. Activated partial thromboplastin time and international normalized ratio <=1.5 x ULN, unless the subject is receiving therapeutic anticoagulants.

Must not have

a. Poorly controlled hypertension (defined as systolic blood pressure [BP] >150 mmHg or diastolic BP >90 mmHg) refractory to medical management.

g. Iron overload sufficiently severe to result in a clinical diagnosis by the Investigator of cardiac (e.g., clinically significant impaired left ventricular ejection fraction), hepatic (e.g., fibrosis, cirrhosis), or pancreatic (e.g., diabetes) dysfunction.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 and 48 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the long-term tolerability and safety of mitapivat (or AG-348) in people with sickle cell disease.

Who is the study for?

Adults aged 18-70 with Sickle Cell Disease (SCD) who previously participated in NIH study #19H0097 and benefited from it. They must have stable organ function, no recent blood transfusions, and for women of childbearing potential, a commitment to use two forms of contraception. Exclusions include significant heart rhythm issues, uncontrolled medical conditions like hypertension or diabetes, active infections or certain drug allergies.

What is being tested?

The trial is testing the long-term safety and effectiveness of mitapivat tablets taken twice daily by people with SCD. It extends a previous study to see if benefits continue or improve over time. Participants will undergo various health assessments including physical exams, blood tests, heart checks (ECG), mobility tests (6-minute walk), echocardiograms for heart/lung function, bone scans (DXA), and health questionnaires.

What are the potential side effects?

While specific side effects are not listed here, participants will monitor any symptoms they experience in a study diary which may include typical drug-related reactions such as digestive discomforts, potential liver enzyme changes due to medication metabolism challenges or other common medication-induced complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a woman who can have children and have a negative pregnancy test.

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My blood clotting tests are within normal limits, unless I'm on blood thinners.

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My kidney function, measured by creatinine levels or filtration rate, is within the normal range.

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I am between 18 and 70 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My high blood pressure is not controlled by medication.

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I have been diagnosed with heart, liver, or pancreas problems due to high iron levels.

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I haven't had a severe infection or needed strong antibiotics in the last 8 weeks.

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I have had a bone marrow or stem cell transplant.

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I have stopped taking strong CYP3A4/5 inhibitors or inducers for the required time before giving consent.

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I have not used blood cell-boosting drugs in the last 90 days.

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I have a blood disorder other than mild issues from blood transfusions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 and 48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 and 48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 and 48 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

measure: Long-term safety and tolerability of mitapivat in subjects with stable sickle cell disease

Secondary study objectives

To evaluate hemoglobin (Hb) response, changes in hemolytic markers, functional status, cardiopulmonary function, and health-related quality of life in SCD subjects maintained on mitapivat long-term.

To evaluate the pharmacokinetic

To monitor SCD-related safety endpoints in SCD subjects maintained on mitapivat long-term.

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: 1Experimental Treatment1 Intervention

Subjects will be treated with a maintenance dose of mitapivat previously assessed for safety and tolerability in the Phase I study for an initial 48 weeks and undergo safety monitoring, evaluation of pharmacokinetics and pharmacodynamics, and assessment of secondary laboratory and clinical endpoints at pre-specified intervals during the study period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mitapivat

2023

Completed Phase 1

~20

0 / 11Eligibility criteria met