A Study of Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)

• ClinicalTrials.gov Identifier: NCT05568225
• Recruitment Status: Recruiting
• First Posted: October 5, 2022
• Last Update Posted: April 10, 2024
• Sponsor: Forma Therapeutics, Inc.
• Information provided by (Responsible Party): Novo Nordisk A/S ( Forma Therapeutics, Inc. )

Tracking Information

• First Submitted Date: September 15, 2022
• First Posted Date: October 5, 2022
• Last Update Posted Date: April 10, 2024
• Actual Study Start Date: November 22, 2022
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2022)

The hematologic improvement based on an erythroid response (HI -E) ≥ 8 weeks duration in patients with MDS after 16 weeks of etavopivat treatment [ Time Frame: 16 weeks ]

Measure in number of patient incidence This endpoint will be based on the combined incidence of:

• Non-transfusion dependent (NTD) patients: ≥ 1.5 g/dL increase in hemoglobin (Hb) from baseline maintained ≥ 8 consecutive weeks
• Low transfusion burden (LTB) patients: absence of any transfusion for ≥ 8 consecutive weeks
• High transfusion burden (HTB) patients: reduction by ≥ 50% of red blood cell (RBC) units for ≥ 8 consecutive weeks

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 30, 2022)

• The HI-E ≥ 8 weeks duration in this population of patients after 24 and 48 weeks of etavopivat treatment [ Time Frame: 24 and 48 weeks ]
  Measure in number of patient incidence This endpoint will be based on the combined incidence of:

  • Non-transfusion dependent (NTD) patients: ≥ 1.5 g/dL increase in hemoglobin (Hb) from baseline maintained ≥ 8 consecutive weeks
  • Low transfusion burden (LTB) patients: absence of any transfusion for ≥ 8 consecutive weeks
  • High transfusion burden (HTB) patients: reduction by ≥ 50% of red blood cell (RBC) units for ≥ 8 consecutive weeks
• The HI-E ≥ 16 weeks duration in this population of patients after 24 and 48 weeks of etavopivat treatment [ Time Frame: 24 and 48 weeks ]
  Measure in number of patient incidence This endpoint will be based on the combined incidence of:

  • Non-transfusion dependent (NTD) patients: ≥ 1.5 g/dL increase in hemoglobin (Hb) from baseline maintained ≥ 16 consecutive weeks
  • Low transfusion burden (LTB) patients: absence of any transfusion for ≥ 16 consecutive weeks
  • High transfusion burden (HTB) patients: reduction by ≥ 50% of red blood cell (RBC) units for ≥ 16 consecutive weeks
• Incidence of AEs, serious adverse events (SAEs), and AEs related to etavopivat [ Time Frame: 4(first 6 participants), 16, 24, and 48 weeks ]
  Measure in number of patient incidences
• Number of premature discontinuations, dose interruptions, and dose reductions [ Time Frame: 4(first 6 participants), 16, 24, and 48 weeks ]
  Measure in number of patient incidences
• Overall response rate for MDS [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in number of patient incidence, per Chelson, 2006 International Working Group [IWG] Criteria
• Duration of response [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in number of days, per 2006 IWG Criteria
• Percentage of participants who achieved RBC transfusion independence in participants with LTB or HTB at study entry [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in percentage
• Change from baseline in RBC units transfused in patients with NTD, LTB or HTB at study entry [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in RBC units
• Participants who achieved a hematologic improvement in neutrophil [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in number of patient incidence
• Participants who achieved a hematologic improvement in platelet response [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in number of patient incidence
• Change from baseline in mean serum ferritin [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in ng/mL
• Change from baseline in mean daily dose of iron chelation therapy [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in dose unit
• Overall survival [ Time Frame: 16, 24, and 48 weeks. ]
  Measure in number of patient incidence

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)
• Official Title: A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Very Low Risk, Low Risk, or Intermediate Risk MDS Per IPSS-R

Intervention

Drug: Etavopivat

400 mg once daily

Other Name: FT-4202

Study Arms

Experimental: Etavopivat 400 mg QD daily

Non-transfusion dependent (NTD), Low transfusion burden (LTB) , and High transfusion burden (HTB) patients

Intervention: Drug: Etavopivat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 30, 2022): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

1. 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.
2. Age ≥ 18 years at time of first dose.
3. 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.

4. 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:

   • < 5% blasts in bone marrow based on local pathology review
   • < Intermediate risk cytogenetic abnormalities per IPSS-R

5. Anemia defined as:

   • Non-transfusion dependent (NTD): Subjects with mean Hb concentration < 10.0 g/dL of 2 measurements (1 performed within 3 days prior to Day 1 and the other performed 7 to 28 days prior to Day 1, not influenced by RBC transfusion within 7 days of measurement) and < 3 RBC transfusions for anemia in the prior 16 weeks before Day 1 of etavopivat dosing

   OR

   • Transfusion dependent (TD): Subjects having received ≥ 3 units of RBCs for the treatment of anemia within 16 weeks prior to Day 1
6. 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.
7. ECOG performance status of ≤ 2
8. Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is contraindicated or not indicated.
9. No alternative treatment options are available and/or appropriate for the subject, at the discretion of the investigator.
10. Patient is willing and able to adhere to the study visit schedule and other protocol requirements

EXCLUSION CRITERIA:

[MDS History]

1. MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality
2. 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

3. Known history of acute myeloid leukemia (AML)

   [Medical Conditions]

4. Female who is breast feeding or pregnant
5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
6. Absolute neutrophil count < 500/µL (0.5 x 10^9/L)
7. Platelet count < 50,000/µL (50 x 10^9/L) without transfusion support within 2 weeks

8. Hepatic dysfunction characterized by:

   • Alanine aminotransferase (ALT) > 5.0 × upper limit of normal (ULN)
   • Total bilirubin > 3.0 × ULN
   • History of cirrhosis
9. 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.

10. Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection.

    • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay Screening/ enrollment until active therapy has been completed.
    • Patients with acute viral infections without available therapies (eg, coronavirus disease 2019 [COVID-19]) should delay Screening/ enrollment until the acute infection has resolved.

    Note: Infection prophylaxis is allowed.

11. Known human immunodeficiency virus (HIV) positivity
12. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive)
13. Active hepatitis C infection

14. History of malignancy, other than MDS, 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, carcinoma in situ of the cervix, or carcinoma in situ of the breast)
    • Patients with incidental histologic findings of prostate cancer (T1a or T1b) are eligible

15. 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
    • Heart disease, heart failure as classified by the New York Heart Association classification 3 or higher, or significant arrhythmia requiring treatment,
    • Pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, ≥ Grade 3 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (or higher)
16. Uncontrolled hypertension, defined as repeated elevation of diastolic blood pressure ≥ 100 mmHg despite adequate treatment

17. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).

    [Prior/Concomitant Therapy]

18. Prior treatment with azacitidine (injectable or oral) or decitabine
19. 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.

20. Prior use of luspatercept:

    • NTD patients must not have received luspatercept within 30 days prior to Day 1 treatment
    • TD patients must not have received luspatercept within 16 weeks prior to Day 1 treatment
21. 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.
22. Prior allogeneic or autologous stem cell transplant

23. Initiation of a new chelation therapy within 3 months before the first dose of study treatment.

    [Prior/Concurrent Clinical Study Experience]

24. 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]

25. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novo Nordisk; (+1) 866-867-7178; clinicaltrials@novonordisk.com

• Listed Location Countries: Canada, France, Germany, United States

Administrative Information

• NCT Number: NCT05568225
• Other Study ID Numbers: 4202-ONC-203
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novo Nordisk A/S ( Forma Therapeutics, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Forma Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Transparency (dept. 2834), MD; Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: April 2024