A Study of Momelotinib in Participants With Low-risk Myelodysplastic Syndrome

NCT06847867 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2235842024-519928-24
• Study Type: interventional
• Target: 80
• Locations: 9 countries
• Sites: 39

Brief Summary

The goal of this clinical trial is to determine if momelotinib is safe and effective for people with low-risk myelodysplastic syndromes (LR-MDS). The trial will also examine how the body processes the drug. The study is comprised of two parts: Part 1: Participants will receive different doses of momelotinib to find the best dose by evaluating effectiveness in improving red blood cell transfusion requirements and safety. Part 2: Participants will receive dose selected from Part 1 to assess its impact on improving red blood cell transfusion requirements and safety in LR-MDS.

Conditions

Myelodysplastic Syndromes

Keywords

Momelotinib; Low-risk Myelodysplastic Syndrome; MIDAS

Outcome Measures

Primary Outcomes (5)

• Part 1: Percentage of participants with Red Blood Cells - transfusion independence (RBC-TI) for at least 12 weeks, rolling over 24 weeks

  RBC-TI defined as not requiring RBC transfusions (except in the case of clinically overt bleeding). Percentage of participants with RBC-TI will be measured for any consecutive 12-week interval over 24-week duration.

  Up to 24 weeks

• Part 1: Number of participants with Grade 3 Adverse events (AEs), AE leading to treatment discontinuation and AEs leading to dose modifications

  Up to approximately 104 weeks

• Part 1: Maximum plasma concentration (Cmax) of momelotinib and major metabolite of momelotinib (M21)

  Up to 24 weeks

• Part 1: Area under the plasma concentration versus time curve (AUC) of momelotinib and M21

  Up to 24 weeks

• Part 2: Percentage of participants with ≥12 weeks of RBC-TI by the end of Week 24

  RBC-TI defined as not requiring RBC transfusions (except in the case of clinically overt bleeding). Percentage of participants with RBC-TI will be measured for any consecutive ≥12-week interval by the end of Week 24.

  At week 24

Secondary Outcomes (16)

• Part 1: Percentage of participants with ≥12 weeks of RBC-TI by the end of Week 24

  At week 24

• Part 1: Number of participants with AEs, Serious adverse events (SAEs), AEs leading to treatment discontinuation, and AEs leading to dose modifications

  Up to approximately 183 weeks

• Part 1: Number of participants with AEs, SAEs, AEs leading to treatment discontinuation, and AEs leading to dose modifications by Severity

  Up to approximately 183 weeks

• Part 1: Number of participants with clinically significant changes in laboratory parameters

  Up to approximately 183 weeks

• Part 1: Number of participants with clinically significant changes in vital signs

  Up to approximately 183 weeks

Study Arms (2)

Part 1- Dose Optimisation: Momelotinib

EXPERIMENTAL

Drug: Momelotinib

Part 2- Dose Exploration: Momelotinib

EXPERIMENTAL

Drug: Momelotinib

Interventions

Momelotinib DRUG

Momelotinib will be administered.

Also known as: GSK3070785

Part 1- Dose Optimisation: Momelotinib; Part 2- Dose Exploration: Momelotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years or of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent form (ICF).
• Documented diagnosis of MDS according to the World Health Organization classifications with an Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease, with an overall risk score ≤3.5.
• \- Refractory to prior treatment: documentation of loss of erythroid (E) response or never achieved HI-E response as defined by the IWG 2018 criteria.
• \- Intolerant to prior treatment: documentation of reasons for discontinuation of prior ESA containing regimen, either as single agent or combination (e.g., G-CSF) or luspatercept due to intolerance or adverse event.
• Red blood cell transfusion dependence, defined as requiring an average of ≥4 units of Packed red blood cells (pRBC) transfused over an 8-week period during the 16 weeks preceding randomization. Documentation of a participant's transfusion policy during this 16-week period is required.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
• a. Is a woman of non-childbearing potential (WONCBP). OR b. Is a woman of childbearing potential (WOCBP) and using a contraceptive method.
• Is capable of giving signed informed consent.
• Eastern Cooperative Oncology Group performance status ≤2.
• Adequate organ function.

You may not qualify if:

• Prior treatment with the following with noted time periods:
• Janus kinase (JAK)1/2 inhibitors; ACTRIIb IMiDs (iif ≤1 week of treatment received; provided last dose was ≥8 weeks from randomization
• ACTRIIb receptor ligand trap other than luspatercept
• Hypomethylating agents or other disease modifying agents (i.e., IMiDs) and immunosuppressive therapy for MDS
• ESA within 4 weeks, or 8 weeks for long-acting ESA.
• Growth factors (i.e., G-CSF, GM-CSF) within 4 weeks.
• Luspatercept within 8 weeks.
• Investigational agents within 4 weeks or 5 half-lives, whichever is longer.
• Corticosteroids for treatment of the underlying disease within 28 days. Supportive care use of steroids for non-MDS indications may be used provided participant is on a stable dose equivalent to ≤10 mg prednisone per day.
• Other active anti-MDS therapy not otherwise listed within 28 days or 5 half-lives whichever is longer.
• Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of momelotinib.
• Has received a live vaccine within 30 days. • Prior allogeneic or autologous stem cell transplant. • Has had any major surgery within 28 days prior to randomization. • Ongoing adverse reaction(s) from prior therapy that have not recovered to ≤Grade 1 or to the baseline status preceding prior therapy, except if the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• MDS associated with del 5q cytogenetic abnormality.
• Secondary MDS (i.e., MDS that is known to have arisen as the result of chemical injury, treatment with chemotherapy, and/or radiation for other diseases).
• Known history of diagnosis of acute myeloid leukemia.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (39)

GSK Investigational Site

Goodyear, Arizona, 85338, United States

RECRUITING

GSK Investigational Site

Duarte, California, 91010-3012, United States

RECRUITING

GSK Investigational Site

Irvine, California, 92618, United States

RECRUITING

GSK Investigational Site

New Haven, Connecticut, 06519-1110, United States

RECRUITING

GSK Investigational Site

Canton, Ohio, 44718, United States

RECRUITING

GSK Investigational Site

Houston, Texas, 77030, United States

RECRUITING

GSK Investigational Site

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

GSK Investigational Site

Le Mans, Sarthe, 72000, France

RECRUITING

GSK Investigational Site

Nice, 06202, France

RECRUITING

GSK Investigational Site

Paris, 75010, France

RECRUITING

GSK Investigational Site

Poitiers, 86021, France

RECRUITING

GSK Investigational Site

Toulouse, 31059, France

RECRUITING

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

GSK Investigational Site

Dresden, 01307, Germany

RECRUITING

GSK Investigational Site

Leipzig, 04103, Germany

RECRUITING

GSK Investigational Site

Udine, Friuli Venezia Giulia, 33100, Italy

RECRUITING

GSK Investigational Site

Rozzano, Milan, 20089, Italy

RECRUITING

GSK Investigational Site

Catania, 95123, Italy

RECRUITING

GSK Investigational Site

Florence, 50134, Italy

RECRUITING

GSK Investigational Site

Milan, 20122, Italy

RECRUITING

GSK Investigational Site

Orbassano to, 10043, Italy

RECRUITING

GSK Investigational Site

Katowice, 40-523, Poland

RECRUITING

GSK Investigational Site

Warsaw, 02-172, Poland

RECRUITING

GSK Investigational Site

Seongnam-si Gyeonggi-do, 13620, South Korea

RECRUITING

GSK Investigational Site

Seoul, 03080, South Korea

RECRUITING

GSK Investigational Site

Seoul, 05505, South Korea

RECRUITING

GSK Investigational Site

Seoul, 06591, South Korea

RECRUITING

GSK Investigational Site

Barcelona, 8035, Spain

RECRUITING

GSK Investigational Site

Barcelona, 8907, Spain

RECRUITING

GSK Investigational Site

Madrid, 28027, Spain

RECRUITING

GSK Investigational Site

Málaga, 29010, Spain

RECRUITING

GSK Investigational Site

Ourense, 032005, Spain

RECRUITING

GSK Investigational Site

PamplonaNavarra, 31008, Spain

RECRUITING

GSK Investigational Site

Salamanca, 37007, Spain

RECRUITING

GSK Investigational Site

Valencia, 46010, Spain

RECRUITING

GSK Investigational Site

Lincoln, LN2 4AX, United Kingdom

RECRUITING

GSK Investigational Site

London, SE5 9RS, United Kingdom

RECRUITING

GSK Investigational Site

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: February 26, 2025
• Study Start: June 5, 2025
• Primary Completion (Estimated): July 14, 2027
• Study Completion (Estimated): December 29, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); DE (3); ES (8); IT (6); PL (2); FR (5); KR (4); CA (2); GB (3)