A Global Phase 3, Randomized, Double-Blind and Placebo-Controlled Study Evaluating the Efficacy and Safety of Etavopivat in Adolescents and Adults with Sickle Cell Disease (HIBISCUS 2 Study)
December 26, 2024| Ongoing Project | Reading time: 8 min
Introduction
Kintampo Health Research Centre (KHRC) is about to start this Phase 3 HIBISCUS 2 study as a follow up to the Phase 2 study to test the effectiveness and safety of the etavopivat (FT-4202) drug in a larger population of adolescents and adults with sickle cell disease (SCD). This four-year study, also funded by Novo Nordisk A/S is trying to find new ways to treat SCD, which is a serious genetic condition that affects millions of people worldwide, including Ghana.
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 (SCD) is a group of genetic disorders of red blood cells characterized by the presence of two abnormal haemoglobins, one of which is haemoglobin S. SCD is inherited in an autosomal recessive pattern in which an individual inherits 2 copies of any combination of abnormal haemoglobin genes. The annual prevalence of SCD among newborns is approximately 2%, and 20% of the Ghanaian population carry the sickle cell trait. The abnormal HBS causes haemoglobin polymerization which distorts erythrocyte membrane leading to sickling and impaired flow and deformability. These changes make the RBCs fragile, easily destroyed, and unable to move smoothly within small blood vessels, thus blocking and depriving organs of blood and oxygen. Currently, there is no cure for SCD. This study aims to test a new disease-modifying drug for the treatment of sickle disease is adolescents and adults.
Objectives
The main objectives of the study are:
1. To demonstrate superiority of treatment with etavopivat versus placebo in adolescents and adults with SCD.
2. To evaluate clinical efficacy measures of etavopivat
treatment versus placebo in adolescents and adults with SCD.
Study Methodology
This is an interventional, multi-national, multi-center, randomized (2:1), double-blind, placebo- controlled phase 3 study in participants aged12 and older with SCD, who had 2−15VOCs in the year prior to screening
and who have moderate to severe anemia.
Participants will be randomized in a blinded fashion (2:1) to the etavopivat or placebo dosing groups. A totalof 408 participants are expected to be enrolled in the study and receive treatment for 52 weeks in the double-blind treatment period. A maximum of 100 participants will be adolescents (12 to 17 years).A maximum of 50% of participants enrolled will have 2−3 VOC in the 12 months prior to screening and a minimum of 50% of participants enrolled will have 4−15 VOCs in the 12 months prior to screening.
Participants will be stratified by age at randomization (12 to 17 or 18 years and older), number of VOCs in the preceding 12 months (2−3, or 4−15) and concomitant disease modifying treatment (e.g., HU or l-glutamine [Endari®]) use at the time of screening (Yes or No). Following randomization, all participants enrolled will continue blinded treatment for 52 weeks.
Following the 52 weeks of double-blind treatment, participants will enter a 52-weeks etavopivat OLE treatment period. Thus, the maximum duration of the treatment period for an individual participant is 104weeks. Participants who do notfinish the 52 double-blind treatment period may not enter the OLE period.
Expected Outcomes
The expected outcomes include a reduction in the number of adjudicated Vaso-occlusive crisis (VOC) event with a medical contact from baseline to week 52 during the blinded treatment period, as well as a change
in hemoglobin (Hb), Change in lactate dehydrogenase (LDH), Change in absolute reticulocyte count, Change in indirect bilirubin from Baseline (week 0) to week 52.
Funder
Novo Nordisk A/S.
Study Duration
Four (4) Years