A Study of Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)
- Conditions
- Very Low Risk, Low Risk, or Intermediate Risk MDS Per IPSS-R
- Interventions
- Registration Number
- NCT05568225
- Lead Sponsor
- Forma Therapeutics, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of etavopivat (FT-4202) for the treatment of anemia in adult patients with very low risk, low risk, or intermediate risk MDS.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Etavopivat 400 mg QD daily Etavopivat Non-transfusion dependent (NTD), Low transfusion burden (LTB) , and High transfusion burden (HTB) patients
- Primary Outcome Measures
Name Time Method Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment From Baseline to Week 24 This outcome measure reported on the combined incidence of NTD, LTB and HTB in terms of (HI-E) response for \>=8 weeks duration in participants with myelodysplastic syndromes (MDS) within 24 weeks. The participants were allocated to the following arms which were defined as: 1) NTD: \>=1.5 grams per deciliter (g/dL) increase in haemoglobin (Hb) from baseline maintained \>=8 consecutive weeks and no transfusion of RBC units for anemia over a continuous 8-week treatment period; 2) LTB: absence of any transfusion for \>=8 consecutive weeks; and 3) HTB: reduction by \>=50 percent (%) of RBC units for \>=8 consecutive weeks.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Hematologic Improvement-Erythroid (HI-E) Response for =>8 Weeks Within 16 and 48 Weeks of Etavopivat 48 weeks This outcome measure focused on the combined incidence of NTD, LTB and HTB participants, evaluating HI-E lasting =\>8 weeks in individuals with MDS within 16 weeks and 48 weeks. Participant's response were defined as follows: 1) NTD: an increase of =\>1.5 g/dL in Hb maintained for =\>8 consecutive weeks without any RBC transfusions for anemia; 2) LTB: no transfusions over =\>8 consecutive weeks; and 3) HTB: a reduction of =\>50% in RBC units for =\>8 consecutive weeks.
Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for =>16 Weeks Within 24 and 48 Weeks of Etavopivat 48 weeks This outcome measure focused on the combined incidence of NDT, LTB and HTB participants, evaluating HI-E response lasting =\>16 weeks in individuals with MDS within 24 weeks and 48 weeks. Participant's response were defined as follows: 1) NTD: an increase of =\>1.5 g/dL in Hb maintained for =\>16 consecutive weeks without any RBC transfusions for anemia; 2) LTB: no transfusions over =\>16 consecutive weeks; and 3) HTB: a reduction of =\>50% in RBC units for =\>16 consecutive weeks.
Number of All Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Related to Etavopivat From baseline up to 48 weeks This outcome measures the total number of AEs and SAEs in participants, including AEs related to etavopivat. AEs are any unfavorable medical occurrences in participants taking the medicinal product, regardless of causality. They include new or worsening symptoms, abnormal lab findings, and exacerbations of existing conditions, documented from the first dose through 28 days after the last dose. SAEs are severe AEs that result in death, are life-threatening, require hospitalization, lead to significant disability, or involve congenital anomalies. Important medical events posing risks to the participants are also classified as SAEs. Treatment Emergent Adverse Events (TEAEs) are AEs occurring after treatment initiation, aiding in the safety assessment of etavopivat. TEAEs will be considered drug-related if assessed by the Investigator as possibly related or related, or if relationship is missing.
Overall Response Rate Up to 48 weeks The Overall Response Rate (ORR) is defined as the percentage of participants who achieve a predefined level of response according to the 2006 International Working Group (IWG) criteria, assessed at each scheduled evaluation.
Number of Premature Discontinuations, Dose Interruptions, and Dose Reductions Within 48 weeks The outcome measures the total number of premature discontinuations, dose interruptions and dose reductions. Premature discontinuation was defined as any discontinuation prior to week 48. A dose interruption is a temporary halt in treatment due to an AE, while a dose reduction involves lowering the dosage of the drug when AEs occur. If a participant tolerates a reduced dose for 14 days, a rechallenge with the original dose may occur after a clinic visit, but any new Grade 3 or higher AEs require treatment discontinuation and consultation with the Global Medical Monitor before resuming.
Percent Change From Baseline in RBC Transfusion Independence for =>8 Weeks in Participants With LTB or HTB at Study Entry Up to 48 weeks This outcome measure is percent change in RBC transfusion by 8-week interval in participants with LTB and HTB. Percent reduction from baseline in RBC transfusion burden is defined as -100×(Total RBC Units Transfused During Interval)/(Baseline RBC Units Transfused Per 8 Weeks).
Duration of Response Up to 48 weeks This outcome measure reported duration of response which was defined as duration of response will be summarized with quantiles based on product limit estimates (ie, Kaplan-Meier). Duration of response is defined as the time from date of first known incidence of a 2006 IWG criteria response to the most recent date that the 2006 IWG (International Working Group) criteria is not met following the initial response. If the participant has met IWG criteria throughout the period following the initial response, the participant will be censored at the latest date of end of study, loss to follow-up, or death.
Reduction in RBC Transfusions for >=8 Weeks in Participants With LTB or HTB at Study Entry Up to 48 weeks This outcome measure reports reduction in RBC transfusion by 8-week interval in participants with LTB and HTB.
Change From Baseline in Neutrophils and/or Platelets Counts Baseline (week 0), week 48 This outcome measure reports the change from baseline in neutrophils and/or platelets counts from baseline to week 48
Overall Survival Within 48 weeks Overall survival is defined as the time from first dose to date of death. If the participant was alive at last contact, the end date will be censored at the latest of either end of study, loss to follow-up, or study discontinuation.
Decrease in Ferritin and Transferrin Saturation (TSAT) Up to 48 weeks This outcome measure were to report decrease in ferritin and TSAT from baseline to Week 48.
Decrease in Iron Chelation Therapy up to 48 weeks This outcome measure were to report decrease of Iron chelation therapy and will be recorded at Screening and on an ongoing basis throughout the study.
Etavopivat Plasma Concentrations Weeks 1 and 4 pre-dose, post-dose 1, 2, 4, 6 hours.Week 2 and EOT (week 48):pre-dose, post-dose 1, 2 hours This outcome measure reported Etavopivat plasma concentrations in order to assess the PK properties of etavopivat in participants with MDS. PK parameters included but not limited to were: Time to maximum observed plasma concentration, area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last), from time zero to infinity (AUC0-inf), for a dosing interval (AUCtau/AUC0-24).) However due to early termination of the study, the PK parameters were not assessed and only the plasma concentrations could be assessed.
RBC 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) Levels Over Time Within 48 weeks Etavopivat plasma concentrations were collected in order to assess the pharmacodynamic (PD) properties of etavopivat in participants with MDS.
Trial Locations
- Locations (18)
University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
Ocala Oncology
🇺🇸Ocala, Florida, United States
Cedars-Sinai Medical Center
🇺🇸Plainsboro, New Jersey, United States
Northwell Health
🇺🇸Plainsboro, New Jersey, United States
Northwestern Memorial Hospital
🇺🇸Plainsboro, New Jersey, United States
The Ohio State University Medical Center
🇺🇸Plainsboro, New Jersey, United States
NYU Langone Health
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
University of British Columbia - St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Nice University Hospital - Hôpital de l'Archet
🇫🇷Route de Saint-Antoine, Nice, France
Scroll for more (8 remaining)University of Miami Hospital and Clinics🇺🇸Miami, Florida, United States