NCT05031780

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

A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Sickle Cell Disease

• Status: Active Not Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 286 (actual)
• Sponsor: Agios Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Mitapivat	Mitapivat tablets
OTHER	Mitapivat-matching placebo	Placebo to match 50 mg or 100 mg tablets
OTHER	Mitapivat-matching placebo	Placebo to match 100 mg tablets

Timeline

• Start date: 2022-02-11
• Primary completion: 2025-10-30
• Completion: 2030-02-01
• First posted: 2021-09-02
• Last updated: 2026-03-30

Locations

91 sites across 16 countries: United States, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Kenya, Lebanon, Netherlands, Nigeria, Oman, Saudi Arabia, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study