An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE Study).

December 26, 2024| Ongoing Project | Reading time: 8 min

Introduction

Kintampo Health Research Centre (KHRC) is carrying out this Phase 2 PRAISE study to explore a new treatment for sickle cell disease (SCD). This study is funded by Novo Nordisk A/S and seeks to test the effectiveness and safety of a drug called FT-4202 in adolescents and adults with sickle cell disease (SCD). The study will compare the effects of FT-4202 to a placebo (a treatment with no active ingredients) in people aged 12 to 65 who have SCD.

Investigators

Dr. Seyram Kaali, Dr. Kwaku Poku Asante, Dr. Samuel Harrison, Dr. Prince Darko Agyapong, Dr. Cynthia Yaa Bema, Dr. Felicia Serwah, Dr. Afia Korkor Opare Yeboah, Dr. David Dosoo, Mr. Kingsley Kayan, Mr. Elvis Ato Wilson, Mr. Zakariah Buwah, Mr. Francis Mensah Kornu.

Background

Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). It is the most common inherited hemolytic anemia, affecting approximately 100,000 patients in the United States (US) (CDC 2020). The global burden is even greater and is expected to continue to rise. The disease is characterized by polymerization of HbS in RBCs when HbS is in the deoxygenated state,resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises resulting in tissue ischemia, infarction, and long-term tissue damage. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia.

Finally, damaged RBCs have abnormal surfaces that adhere to and damage vascular endothelium, provoking a proliferative/inflammatory response that underlies large-vessel stroke and potentially pulmonary- artery hypertension. Collectively, these contribute to the significant morbidity and increased mortality associated with this disease.

Currently, therapeutic treatment of SCD is inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies, are invasive andsuch high-risk procedures are limited to only a subset of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. While inducing HbF can be effective therapeutically, HU can be myelosuppressive and is a teratogen (Sampson et al. 2010). Although HU is considered to have an acceptable therapeutic index, the myelosuppressive and teratogenic risks limit its effectiveness.

Objectives
The main objectives of the study are:

1. To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in haemoglobin (Hb).

2. To assess the efficacy of FT-4202 as compared to placebo on the annualized Vaso-occlusive crisis (VOC) rate.

Study Methodology
This study is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study of patients, age 12 to 65 years (inclusive), with SCD. Participants under rigorous screening to select only those who meet strict eligibility criteria. Following eligibility assessment, patients are randomized to receive the FT-4202 or pacebo. In the phase portion of the study, a randomization ratio of 1:1:1 to one of two dose levels of FT-4202 or placebo (dose determination portion) was used. The higher dosing regimen was selected for further evaluation in the phase 3 portion of the study. Participants are currently being enrolled into the phase 3 component. Overall study duration is 104 weeks including a 52-week double blind phase and another 52-week open-label extension phase.

Expected Outcomes
The study is expected to show whether FT-4202 can increase hemoglobin levels at week 24 (increase of > 1 g/dL from baseline) during the blinded treatment period and reduce the number of painful episodes over the course of the 52-week blinded treatment period.

Funder
Sanofi Pasture Inc.

Study Duration
Study Duration: Three (3) Years
Start Date: July 2023
End Date: November 2026