Mitapivat for Anemia, Sickle Cell

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Hôpital Erasme, Anderlecht, Belgium
Anemia, Sickle Cell+1 More
Mitapivat - Drug
Eligibility
Any Age
All Sexes
Eligible conditions
Select

Study Summary

A Study Evaluating the Efficacy and Safety of Mitapivat (AG-348) in Participants With Sickle Cell Disease

See full description

Eligible Conditions

  • Anemia, Sickle Cell
  • Sickle Cell Disease (SCD)

Treatment Effectiveness

Study Objectives

This trial is evaluating whether Mitapivat will improve 4 primary outcomes and 36 secondary outcomes in patients with Anemia, Sickle Cell. Measurement will happen over the course of Up to Week 12.

Week 12
Phase 2: Change From Baseline in Absolute Reticulocytes Count
Phase 2: Change From Baseline in Erythropoietin
Phase 2: Change From Baseline in Hb Concentration
Phase 2: Change From Baseline in Indirect Bilirubin
Phase 2: Change From Baseline in Lactate Dehydrogenase (LDH)
Phase 2: Change From Baseline in Patient-Reported Outcomes Measurement Information System® (PROMIS®) Fatigue 13a Short Form (SF) Score
Phase 2: Change From Baseline in Percent Reticulocytes
Week 24
Phase 3: Change From Baseline in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact
Phase 3: Change From Baseline in PROMIS Pain Intensity
Week 52
Phase 3: Change From Baseline in Absolute Reticulocytes
Phase 3: Change From Baseline in Erythropoietin
Phase 3: Change From Baseline in Hb Concentration
Phase 3: Change From Baseline in Indirect Bilirubin
Phase 3: Change From Baseline in LDH Concentration
Phase 3: Change From Baseline in PROMIS® Fatigue 13a SF Scores
Phase 3: Change From Baseline in Percent Reticulocytes
Baseline, Week 52
Phase 3: Change From Baseline in 6-Minute Walk Test (6MWT)
Phase 3: Change From Baseline in PGIS of Pain
Phase 3: PGIC of Pain
Week 24
Phase 3: Percentage of Participants With Improvement in the Patient Global Impression of Change (PGIC) -Fatigue
Phase 3: Percentage of Participants With Improvement in the Patient Global Impression of Severity (PGIS) -Fatigue
Week 40
Phase 3: Mitapivat Area Under the Concentration Curve
Phase 3: Mitapivat Concentration Over Time
Phase 3: Mitapivat Maximum (Peak) Concentration
Phase 3: Pharmacokinetic/Pharmacodynamic Relationship: Evaluate the Exposure of Mitapivat to the Change in ATP and 2,3-DPG Levels
Week 8
Phase 2: Mitapivat Area Under the Concentration
Phase 2: Mitapivat Concentration Over Time
Phase 2: Mitapivat Maximum (Peak) Concentration
Phase 2: Pharmacokinetic/Pharmacodynamic Relationship: Evaluate the Exposure of Mitapivat to the Change in Adenosine Triphosphate (ATP) and 2,3-Diphosphoglycerate (2,3-DPG)
Up to 56 weeks
Phase 3: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious AEs (SAEs)
Up to Week 12
Phase 2: Annualized Rate of SCPCs
Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious AEs (SAEs)
Up to Week 52
Phase 3: Annualized Frequency of Hospitalizations for SCPC
Phase 3: Annualized Rate of Emergency Room Visits for SCPC
Phase 3: Annualized Rate of Hospitalization Days for SCPC
Phase 3: Annualized Rate of Sickle Cell Pain Crises (SCPCs)
Phase 3: Time to First SCPC
Phase 3: Time to Second SCPC
Week 12
Phase 2: Percentage of Participants With Hemoglobin (Hb) Response
Week 52
Phase 3: Percentage of Participants With Hb Response

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

7 Treatment Groups

Phase 2: Open-Label Extension Period
1 of 7
Phase 3: Mitapivat selected Phase 3 dose
1 of 7
Phase 2: Mitapivat 50 mg BID
1 of 7
Phase 2: Mitapivat 100 mg BID
1 of 7
Phase 3: Open-Label Extension Period
1 of 7
Phase 2: Placebo
1 of 7
Phase 3: Placebo
1 of 7
Experimental Treatment
Non-Treatment Group

This trial requires 267 total participants across 7 different treatment groups

This trial involves 7 different treatments. Mitapivat is the primary treatment being studied. Participants will be divided into 5 treatment groups. Some patients will receive a placebo treatment. The treatments being tested are in Phase 2 & 3 and have had some early promising results.

Phase 2: Open-Label Extension Period
Drug
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.
Phase 3: Mitapivat selected Phase 3 dose
Drug
Double-blind Period: Mitapivat selected Phase 3 dose (50 mg or 100 mg BID) for 52 weeks.
Phase 2: Mitapivat 50 mg BID
Drug
Double-blind Period: Mitapivat 50 milligrams (mg) twice daily (BID) for 12 weeks.
Phase 2: Mitapivat 100 mg BID
Drug
Double-blind Period: Mitapivat 100 mg BID for 12 weeks.
Phase 3: Open-Label Extension Period
Drug
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.
Phase 2: Placebo
Other
Double-blind Period: Mitapivat-matching placebo for 12 weeks.
Phase 3: Placebo
Other
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.

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline, weeks 24, 28, 40, and 52
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly baseline, weeks 24, 28, 40, and 52 for reporting.

Closest Location

Penn Medicine - University of Pennsylvania Health System - Philadelphia, PA

Eligibility Criteria

This trial is for patients born any sex of any age. There are 6 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
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.

Patient Q&A Section

What are common treatments for sickle cell disease (scd)?

"A wide variety of medications are used to treat children and adults with SCD. The use of hydroxycarbamide, splenectomy, bone marrow transplantation, and regular medical exam and evaluation are common. Physicians must be aware of this variety of treatments for SCD." - Anonymous Online Contributor

Unverified Answer

What causes sickle cell disease (scd)?

"It is a genetic trait with different probabilities of developing sickle cell syndromes that is often unexposed to environmental hazards or drugs of abuse. It is caused by a mutation (a change of one or more nucleotides in the DNA of a cell) in one of the genes of sickle hematopoietic cells leading to their production." - Anonymous Online Contributor

Unverified Answer

How many people get sickle cell disease (scd) a year in the United States?

"About 40,000 children under 15 years of age have SCD at some time, of which 24,000 will have an affected parent. The number of children in the United States with SCD will diminish over the next decade, probably due to increased surveillance of SCD and improved treatment of newborns by universal screening." - Anonymous Online Contributor

Unverified Answer

What is sickle cell disease (scd)?

"In infants and children, SCD is marked by anemia, thrombocytopenia and vascular and organ damage due to sickling. In adults, SCD is a serious disease caused mainly by the progressive destruction and disability of the vasculature, heart, brain, liver, kidneys and joints. The average life expectancy in the developed world for people with a single SCD allele is now more than half that of the general population." - Anonymous Online Contributor

Unverified Answer

What are the signs of sickle cell disease (scd)?

"In this population, symptoms of SCD are likely to have been present during childhood, and they include a history of painful crises, splenomegaly, and hepatomegaly; or a previous history of one, two, or three episodes during childhood. It is possible to diagnose SCD based on examination of a peripheral blood smear." - Anonymous Online Contributor

Unverified Answer

Can sickle cell disease (scd) be cured?

"SCD is a chronic autoimmune disorder and therefore it is impossible to alter the number of blood cells in the peripheral blood stream or to totally remove all cells affected by autoimmunity." - Anonymous Online Contributor

Unverified Answer

Does sickle cell disease (scd) run in families?

"SCD is inherited in families. The likelihood of developing SCD in a sibling of a parent with SCD is significantly higher than previously accepted. Results from a recent paper of this study suggest that there are at least two genetic factors that play a role in SCD. Such factors should be identified as molecular markers of SCD to enable the prediction of a genetic predisposition for future development of SCD." - Anonymous Online Contributor

Unverified Answer

What are the common side effects of mitapivat?

"Mitapivat was well tolerated, and the side effects profile generally mirrored that of a non-cancer drug of this class. However, the occurrence of mild and transient reductions in red blood cell counts has been observed in some studies and warrants further investigation in clinical trial cohorts." - Anonymous Online Contributor

Unverified Answer

Is mitapivat safe for people?

"Mitapivat showed high blood pressure and high levels of creatinine and a low haematocrit, which may interfere with the clinical effects of mitapivat. The safety of mitapivat has not been established for people with SCD, and mitapivat should be used with care in this group. More evidence of safety in people with SCD is also warranted to establish mitapivat as a reasonable first-line treatment in this group." - Anonymous Online Contributor

Unverified Answer

Does mitapivat improve quality of life for those with sickle cell disease (scd)?

"Mitapivat significantly reduced the perceived burden and impairment in quality of life for both children with SCD and their caregivers. Parents of patients with SCD are also highly supportive of this medication." - Anonymous Online Contributor

Unverified Answer

How serious can sickle cell disease (scd) be?

"There is a substantial mortality during the course of the disease after the acute event is gone and the disease is stable even in the absence of treatments. This highlights the potential of this disease to become a burden for developing countries, especially in people of African derivation." - Anonymous Online Contributor

Unverified Answer

Has mitapivat proven to be more effective than a placebo?

"Recent findings of the present trial show that MPA was effective in decreasing the frequency of adverse clinical events, a decrease in sickle cell crisis, and a higher percentage of patients who achieved a 50% reduction in the frequency of painful crises. Recent findings show that MPA can be effective in controlling thalassemia pain." - Anonymous Online Contributor

Unverified Answer
Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.
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