A Study of Etavopivat in Patients With Thalassemia or Sickle Cell Disease (GLADIOLUS)

A Phase 2 Open-Label Study to Evaluate Safety and Clinical Activity of Etavopivat in Patients With Thalassemia or Sickle Cell Disease

This clinical trial is a Phase 2 study that will evaluate the safety and clinical activity of etavopivat in patients with thalassemia or sickle cell disease and test how well etavopivat works to lower the number of red blood cell transfusions required and increase hemoglobin.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Thalassemia
• Intervention / Treatment: Drug: Etavopivat tablets

Detailed Description

Etavopivat is a potent, selective, orally bioavailable, small-molecule activator of pyruvate kinase red blood cell (PKR) being developed by Forma Therapeutics, Inc and is intended for use as a treatment for patients with sickle cell disease (SCD) or other inherited hemoglobinopathies or refractory anemias. This study is a multicenter, Phase 2, open-label, multiple-cohort study examining the safety and efficacy of etavopivat for the treatment of patients, age 12 to 65 years, with SCD or thalassemia. Three treatment cohorts based on the patients hemoglobinopathy (SCD or thalassemia) and transfusion requirements will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L4W 4XI
      • Master Centre for Canada
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network - Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine Mother and Child University Hospital
• Egypt
  • Cairo, Egypt, 12613
    • Cairo University
  • Cairo, Egypt, Egypt, 4241317
    • Abu El-Reesh El-Mounira Children University Hospital
• Italy
  • Genova, Italy, 16128
    • Galliera Hospital Centro Anemie Congenite
  • Milan, Italy, 20122
    • Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
  • Naples, Italy, 80138
    • A.O.U. Università Studi della Campania "Luigi Vanvitelli"
  • Napoli, Italy, 80131
    • AORN A. Cardarelli
• Lebanon
  • Baabda, Lebanon, RGWX 4CG
    • Chronic Care Center
  • Tripoli, Lebanon, 1434
    • Hospital Nini
• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Sandwell and West Birmingham NHS Trust SCAT/ haematology
  • London, United Kingdom, SE5 9RS
    • Kings College London
  • London, United Kingdom, E1 1FR
    • Barts Health NHS Trust - The Royal London Hospital
  • London, United Kingdom, NW1 2PG
    • University College Hospital - University College London Hospitals NHS Foundation Trust
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital - London
  • Manchester, United Kingdom, M13 9WL
    • Manchester University Nhs Foundation Trust
• United States
  • California
    • Cerritos, California, United States, 90703
      • TOI Clinical Research
    • Los Angeles, California, United States, 90027
      • [Legal] Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90095
      • University of Californ LA-UCLA
    • Oakland, California, United States, 94609
      • UCSF Oakland Benioff ChildHosp
    • Orange, California, United States, 92868
      • UCI Health
    • Orange, California, United States, 92868
      • [Legal] Children's Hospital of Orange County on behalf of CHOC Children's Hospital of Orange County
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Health Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Hospital of Atlanta
  • Michigan
    • Detroit, Michigan, United States, 48201-2018
      • [Legal] Dr. Vince Clinical Research, LLC and Dr. Vince Clinical Research, P.A.
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Greenville, North Carolina, United States, 27858
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • [Legal] Children's Hospital Medical Center dba Cincinnati Children's
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hosptl Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of consent
• Female patients of childbearing potential must use acceptable methods of contraception, male patients are willing to use barrier methods of contraception

Cohort A (Sickle Cell Disease Transfusion Cohort)

• Confirmed diagnosis of sickle cell disease
• Chronically red blood cell transfused (sample or exchange [manual or via electrophoresis]) for primary stroke prevention or due to previous stroke. Chronic red blood cell transfusion is defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period
• At least 24 months of chronic monthly red blood cell transfusions for secondary stroke prevention/treatment of primary stroke (initial completed overt clinical stroke with documented infarction on brain computed tomography [CT] or magnetic resonance imaging [MRI])
• Prior to screening OR at least 12 months of chronic RBC transfusions for primary stroke prevention (abnormal TCD) prior to screening
• Documented adequate monthly transfusions with average HbS ≤ 45% (the upper limit of the established academic community standard) for the previous 12 weeks of red blood cell transfusions before the first dose of study treatment

Cohort B (Thalassemia Transfusion Cohort)

• Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant
• Chronically transfused, defined as: ≥ 6 red blood cell units in the previous 24 weeks before the first dose of study treatment and no transfusion-free period for > 35 days during that period

Cohort C (Thalassemia Non-transfused Cohort)

• Documented diagnosis of β-thalassemia, Hemoglobin E/ β-thalassemia or Hemoglobin H (α-thalassemia), or other thalassemia variant
• Hemoglobin ≤ 10 g/dL

Exclusion Criteria:

• Female who is breast feeding or pregnant

• Hepatic dysfunction characterized by:

  • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN)
  • Direct bilirubin > 3.0 × ULN
  • History of cirrhosis
• Known human immunodeficiency virus (HIV) positivity
• Active hepatitis B or hepatitis C infection
• Severe renal dysfunction or on chronic dialysis

• History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation.

  • Patients with malignancy considered surgically cured are eligible (eg, non- melanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [Stage 1], Grade 1 endometrial cancer)

• History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:

  • Unstable angina pectoris or myocardial infarction or elective coronary intervention
  • Congestive heart failure requiring hospitalization
  • Uncontrolled clinically significant arrhythmias
  • Symptomatic pulmonary hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etavopivat 400 mg daily - SCD with transfusions; Patients with sickle cell disease on chronic red blood cell transfusions	Drug: Etavopivat tablets; Etavopivat 400 mg once daily; Other Names: FT-4202
Experimental: Etavopivat 400 mg daily - Thalassemia with transfusions; Patients with thalassemia on chronic red blood cell transfusions	Drug: Etavopivat tablets; Etavopivat 400 mg once daily; Other Names: FT-4202
Experimental: Etavopivat 400 mg daily - Thalassemia; Patients with thalassemia not on chronic red blood cell transfusions	Drug: Etavopivat tablets; Etavopivat 400 mg once daily; Other Names: FT-4202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts A: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history	Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history	12 weeks
Cohorts B: Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history	Proportion of patients with ≥ 20% reduction in red blood cell transfusions over a continuous 12-week treatment period versus baseline red blood cell transfusion history	12 weeks
Cohort C: Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)	Hemoglobin response rate at Week 12 (increase of ≥ 1.0 g/dL from baseline)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort A: Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history	Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history	12 weeks
Cohort B: Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history	Proportion of patients with ≥ 33% reduction in red blood cell transfusion over a continuous 12-week treatment period versus baseline red blood cell transfusion history	12 weeks
Cohort A: Reduction in red blood cell transfusions over 12 weeks	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Cohort A: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Cohort A: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Cohort B: Reduction in red blood cell transfusions over 12 weeks	Reduction in red blood cell transfusions over 12 weeks	12 weeks
Cohort B: Reduction in red blood cell transfusions over 24 weeks	Reduction in red blood cell transfusions over 24 weeks	24 weeks
Cohort B: Reduction in red blood cell transfusions over 48 weeks	Reduction in red blood cell transfusions over 48 weeks	48 weeks
Cohort C: Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).	Hemoglobin response rate at Week 24 (increase of ≥ 1.0 g/dL from baseline).	24 weeks
Cohort C: Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).	Hemoglobin response rate at Week 48 (increase of ≥ 1.0 g/dL from baseline).	48 weeks
Change from baseline in hemoglobin over 12 weeks	Change from baseline in hemoglobin over 12 weeks	12 weeks
Change from baseline in hemoglobin over 24 weeks	Change from baseline in hemoglobin over 24 weeks	24 weeks
Change from baseline in hemoglobin over 48 weeks	Change from baseline in hemoglobin over 48 weeks	48 weeks
Changes in serum ferritin levels at 12 weeks versus baseline	Changes in serum ferritin levels at 12 weeks versus baseline	12 weeks
Changes in serum ferritin levels at 24 weeks versus baseline	Changes in serum ferritin levels at 24 weeks versus baseline	24 weeks
Changes in serum ferritin levels at 48 weeks versus baseline	Changes in serum ferritin levels at 48 weeks versus baseline	48 weeks
Changes in liver iron concentration at 48 weeks versus baseline	Changes in liver iron concentration at 48 weeks versus baseline	48 weeks

Collaborators and Investigators

• Sponsor: Forma Therapeutics, Inc.
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Publications and helpful links

Helpful Links

• https://gladiolusstudy.com

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Actual): September 3, 2025
• Study Completion (Actual): September 24, 2025

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Estimated): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hemoglobin; vaso-occlusive crisis; anemia; transfusions; sickle cell disease; transfusion; SCD; sickle cell anemia; VOC; sickle cell; pain crisis; pyruvate kinase; thalassemia; hematologic disease; hemolytic; hemoglobinopathy; beta-thalassemia; vaso-occlusive events; sickle cell crisis; pain episode; congenital anemia; hemolytic anemia; hemoglobinopathies; genetic disease; inborn disease; sickle cell trait; PKR; alpha-thalassemia; hemoglobin H; transfusion-dependent; non-transfusion dependent; hemoglobin E
• Additional Relevant MeSH Terms: Pathologic Processes; Anemia, Hemolytic, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Anemia, Sickle Cell; Thalassemia; beta-Thalassemia; Anemia; alpha-Thalassemia; Hemolysis; Hematologic Diseases; Hemoglobinopathies; Anemia, Hemolytic; Sickle Cell Trait; Vaso-Occlusive Crises
• Other Study ID Numbers: 4202-HEM-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No