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Futility assessment concluded low likelihood of the trial showing meaningful patient benefit.
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Etavopivat 400 mg QD daily | Experimental | Non-transfusion dependent (NTD), Low transfusion burden (LTB) , and High transfusion burden (HTB) patients |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Etavopivat | Drug | 400 mg once daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment | 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. | From Baseline to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Hematologic Improvement-Erythroid (HI-E) Response for =>8 Weeks Within 16 and 48 Weeks of Etavopivat | 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. |
Not provided
INCLUSION CRITERIA:
Patient has provided documented informed consent; the informed consent form (ICF) must be reviewed and signed by each patient prior to any study-related assessments/procedures being conducted.
Age ≥ 18 years at time of first dose.
Patients, if female and of childbearing potential, must agree to use acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.
Documented diagnosis of idiopathic/de novo MDS according to World Health Organization (WHO) classification that meets the IPSS-R classification of very low, low, or intermediate risk disease, and:
Anemia defined as:
OR
Serum erythropoietin level > 200 U/L, OR, if ≤ 200 U/L, subject is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents, or erythropoiesis-stimulating agents are contraindicated or unavailable.
ECOG performance status of ≤ 2
Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is contraindicated or not indicated.
No alternative treatment options are available and/or appropriate for the subject, at the discretion of the investigator.
Patient is willing and able to adhere to the study visit schedule and other protocol requirements
EXCLUSION CRITERIA:
[MDS History]
MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality
Therapy-associated MDS (eg. t-MDS) that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases
Known history of acute myeloid leukemia (AML)
[Medical Conditions]
Female who is breast feeding or pregnant
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
Absolute neutrophil count < 500/µL (0.5 x 10^9/L)
Platelet count < 50,000/µL (50 x 10^9/L) without transfusion support within 2 weeks
Hepatic dysfunction characterized by:
Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m^2 ) or on chronic dialysis.
Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection.
Note: Infection prophylaxis is allowed.
Known human immunodeficiency virus (HIV) positivity
Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive)
Active hepatitis C infection
History of malignancy, other than MDS, within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation.
History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
Uncontrolled hypertension, defined as repeated elevation of diastolic blood pressure ≥ 100 mmHg despite adequate treatment
Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).
[Prior/Concomitant Therapy]
Prior treatment with azacitidine (injectable or oral) or decitabine
Use of erythropoietin, other hematopoietic growth factor treatment or lenalidomide within 30 days of starting study treatment or anticipated need for such agents during the study.
Prior use of luspatercept:
Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP)3A4/5 (see Appendix F) within 2 weeks of starting study treatment or anticipated need for such agents during the study.
Prior allogeneic or autologous stem cell transplant
Initiation of a new chelation therapy within 3 months before the first dose of study treatment.
[Prior/Concurrent Clinical Study Experience]
Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).
[Other Exclusions]
Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Transparency (dept. 2834), MD | Novo Nordisk A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Hospital and Clinics | Miami | Florida | 33136 | United States | ||
| Ocala Oncology |
The study was planned for 58 weeks, including 6 weeks for screening, 24 weeks for treatment, 24 weeks for extension, and 4 weeks for follow-up. It was terminated early after meeting a predefined quality tolerance limit (QTL). Of the 45 participants targeted, only 24 were screened, and 17 were enrolled into three groups: Non-transfusion dependent (NTD) N=3, Low transfusion burden (LTB) N=5, and High transfusion burden (HTB) N=9. Each participant received 400 mg of etavopivat daily.
The trial was conducted at 10 sites in 4 countries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Non-transfusion Dependent | Non transfusion dependent participants who had received less than equal to <= 2 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| FG001 | Low Transfusion Burden |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Primary Treatment Period |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 31, 2023 | Jul 15, 2025 |
Not provided
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| 48 weeks |
| Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for =>16 Weeks Within 24 and 48 Weeks of Etavopivat | 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. | 48 weeks |
| Number of All Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Related to Etavopivat | 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. | From baseline up to 48 weeks |
| Number of Premature Discontinuations, Dose Interruptions, and Dose Reductions | 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. | Within 48 weeks |
| Overall Response Rate | 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. | Up to 48 weeks |
| Duration of Response | 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. | Up to 48 weeks |
| Reduction in RBC Transfusions for >=8 Weeks in Participants With LTB or HTB at Study Entry | This outcome measure reports reduction in RBC transfusion by 8-week interval in participants with LTB and HTB. | Up to 48 weeks |
| Percent Change From Baseline in RBC Transfusion Independence for =>8 Weeks in Participants With LTB or HTB at Study Entry | 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). | Up to 48 weeks |
| Change From Baseline in Neutrophils and/or Platelets Counts | This outcome measure reports the change from baseline in neutrophils and/or platelets counts from baseline to week 48 | Baseline (week 0), week 48 |
| Decrease in Ferritin and Transferrin Saturation (TSAT) | This outcome measure were to report decrease in ferritin and TSAT from baseline to Week 48. | Up to 48 weeks |
| Decrease in Iron Chelation Therapy | 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. | up to 48 weeks |
| Overall Survival | 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. | Within 48 weeks |
| Etavopivat Plasma Concentrations | 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. | 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 |
| RBC 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) Levels Over Time | Etavopivat plasma concentrations were collected in order to assess the pharmacodynamic (PD) properties of etavopivat in participants with MDS. | Within 48 weeks |
| Ocala |
| Florida |
| 34474 |
| United States |
| Cedars-Sinai Medical Center | Plainsboro | New Jersey | 08536 | United States |
| Northwell Health | Plainsboro | New Jersey | 08536 | United States |
| Northwestern Memorial Hospital | Plainsboro | New Jersey | 08536 | United States |
| The Ohio State University Medical Center | Plainsboro | New Jersey | 08536 | United States |
| NYU Langone Health | New York | New York | 10016 | United States |
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
| University of British Columbia - St. Paul's Hospital | Vancouver | British Columbia | V6Z 2K5 | Canada |
| Nice University Hospital - Hôpital de l'Archet | Route de Saint-Antoine | Nice | 06200 | France |
| Hopital Saint Louis | Paris | France |
| Master centre for France | Paris La Défense | 92936 | France |
| Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-1 | Pessac | 33600 | France |
| Universitoetsklinikum Heidelberg | Heidelberg | Germany |
| Charite Universitätsmedizin Berlin | Mainz | 55124 | Germany |
| Universitätsklinikum Leipzig, Klinik und Poliklinik | Mainz | 55124 | Germany |
| Universitaetsklinikum Muenster | Münster | Germany |
| Universitoetsklinikum Halle (Saale) | Münster | Germany |
Low transfusion burden participants who had received 3 to 7 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| FG002 | High Transfusion Burden | High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| Efficacy Evaluable Set (EES) |
|
| Safety Population |
|
| Full Analysis Set (FAS) |
|
| Pharmacokinetic (PK) Set |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Extension Treatment Period |
|
|
FAS included all participants who signed the informed consent and received at least 1 dose of etavopivat.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Non-transfusion Dependent | Non transfusion dependent participants who had received less than equal to <= 2 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| BG001 | Low Transfusion Burden | Low transfusion burden participants who had received 3 to 7 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| BG002 | High Transfusion Burden | High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment | 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. | EES: All participants in the FAS who have completed the week 24 response visit and who have a baseline record of the primary endpoint. | Posted | Number | Percentage of participants | From Baseline to Week 24 |
|
|
| ||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Hematologic Improvement-Erythroid (HI-E) Response for =>8 Weeks Within 16 and 48 Weeks of Etavopivat | 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. | FAS: All participants who signed the informed consent and received at least 1 dose of etavopivat. Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in statistical analysis plan (SAP). | Posted | 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for =>16 Weeks Within 24 and 48 Weeks of Etavopivat | 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. | FAS: All participants who signed the informed consent and received at least 1 dose of etavopivat. Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of All Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Related to Etavopivat | 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. | Safety population includes all participants who received at least one dose of etavopivat (including partial dosing). | Posted | Number | Events | From baseline up to 48 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Premature Discontinuations, Dose Interruptions, and Dose Reductions | 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. | Safety population included all participants who receive at least one dose of etavopivat (including partial dosing). | Posted | Number | Events | Within 48 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Overall Response Rate | 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. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | Up to 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Duration of Response | 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. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | Up to 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Reduction in RBC Transfusions for >=8 Weeks in Participants With LTB or HTB at Study Entry | This outcome measure reports reduction in RBC transfusion by 8-week interval in participants with LTB and HTB. | EES: All participants in the FAS who have completed the week 24 response visit and who have a baseline record of the primary endpoint. n (number analysed) = Participants with available data for a specified category. | Posted | Mean | Standard Deviation | Total RBS units | Up to 48 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Percent Change From Baseline in RBC Transfusion Independence for =>8 Weeks in Participants With LTB or HTB at Study Entry | 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). | EES: All participants in the FAS who have completed the week 24 response visit and who have a baseline record of the primary endpoint. n (number analysed) = participants with available data for a specified category. | Posted | Mean | Standard Deviation | Percent change of total RBC units | Up to 48 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Neutrophils and/or Platelets Counts | This outcome measure reports the change from baseline in neutrophils and/or platelets counts from baseline to week 48 | The Safety Set includes all participants who receive at least one dose of etavopivat (including partial dosing). Here, n (number analysed) = Participants with available data for a specified category. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline (week 0), week 48 |
| |||||||||||||||||||||||||||||||||
| Secondary | Decrease in Ferritin and Transferrin Saturation (TSAT) | This outcome measure were to report decrease in ferritin and TSAT from baseline to Week 48. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | Up to 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Decrease in Iron Chelation Therapy | 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. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | up to 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | 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. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | Within 48 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Etavopivat Plasma Concentrations | 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. | The PK set includes all safety set participants who have at least one evaluable concentration for etavopivat at a scheduled PK time point after the start of dosing. Here, n (number analysed) = Participants with available data for a specified category. | Posted | Mean | Standard Deviation | ng/mL | 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 |
| |||||||||||||||||||||||||||||||||
| Secondary | RBC 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) Levels Over Time | Etavopivat plasma concentrations were collected in order to assess the pharmacodynamic (PD) properties of etavopivat in participants with MDS. | Data for this outcome is not analyzed due to early study termination and have been excluded from planned analyses as prespecified in SAP. | Posted | Within 48 weeks |
|
Up to 48 weeks
All presented AEs are treatment emergent AEs (TEAE). TEAE is defined as any adverse event that emerges or worsens in the period from first dose of study drug to 28 days after the last dose of study drug. Safety population includes all participants who receive at least one dose of etavopivat (including partial dosing).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Non-transfusion Dependent | Non transfusion dependent participants who had received less than equal to <= 2 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG001 | Low Transfusion Burden | Low transfusion burden participants who had received 3 to 7 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. | 0 | 5 | 0 | 5 | 5 | 5 |
| EG002 | High Transfusion Burden | High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. | 0 | 9 | 3 | 9 | 8 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina pectoris | Cardiac disorders | MedDRA 25 | Systematic Assessment |
| |
| Arterial rupture | Vascular disorders | MedDRA 25 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 25 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 25 | Systematic Assessment |
| |
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA 25 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 25 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 25 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 25 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Atrioventricular block second degree | Cardiac disorders | MedDRA 25 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 25 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 25 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| External ear inflammation | Ear and labyrinth disorders | MedDRA 25 | Systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Haemosiderosis | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 25 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Hypervolaemia | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 25 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 25 | Systematic Assessment |
| |
| Iron overload | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Lip infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Mucosal dryness | General disorders | MedDRA 25 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 25 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 25 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25 | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 25 | Systematic Assessment |
| |
| Troponin I increased | Investigations | MedDRA 25 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 25 | Systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA 25 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 25 | Systematic Assessment |
|
The futility assessment concluded low likelihood of the trial showing meaningful participant benefit. The decision was based on a predefined QTL that required 5 or more participants to complete 16 weeks of treatment or not having 8 or more consecutive weeks of primary endpoint data. However 7 participants did not fulfill this requirement, leading to the early termination of the study.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Reporting Office (2834) | Novo Nordisk A/S | (+1) 866-867-7178 | clinicaltrials@novonordisk.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 23, 2024 | Jul 15, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| Lack of Efficacy |
|
| Male |
|
| Race: Not reported |
|
| Ethnicity: Hispanic or Latino |
|
| Ethnicity: Not Reported |
|
| High Transfusion Burden |
High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
| High Transfusion Burden |
High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
Low transfusion burden participants who had received 3 to 7 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks.
| OG002 | High Transfusion Burden | High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
|
| High Transfusion Burden |
High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
|
| Participants |
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
| OG002 | High Transfusion Burden | High transfusion burden participants who had received greater than equal >= 8 RBC transfusions for anaemia within the prior 16 weeks, orally received 400 mg of etavopivat once daily for up to 48 weeks. |
|
|
| Units | Counts |
|---|---|
| Participants |
|