A Phase 2 Study of Momelotinib in Participants with low-risk myelodysplastic syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Aug 2025 → ongoing

Decision date (initial)

2025-08-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

GlaxoSmithKline Research & Development Limited

External identifiers

EU CT number

2024-519928-24-00

ClinicalTrials.gov

NCT06847867

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

Part 1
To identify the RP2D
Part 2
To assess the effect of momelotinib on RBC TI response by Week 24

Secondary objectives 6

1. Part 1 - To assess the effect of momelotinib on RBC-TI response by Week 24
2. - To characterize the safety and tolerability of momelotinib at Dose Level 1 and Dose Level 2 inparticipants with LR-MDS
3. - To describe the exposure of momelotinib and M21
4. Part 2 - To assess the effect of momelotinib on other anemia-related improvement measures
5. - To further characterize the safety and tolerability of momelotinib at RP2D in LR-MDS
6. - To describe the exposure of momelotinib and M21

Conditions and MedDRA coding

Myelodysplastic Syndrome

Study design 8 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants are eligible to be included in the study only if all of the following criteria apply. 1. 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 ICF.
2. 2. Documented diagnosis of MDS according to the World Health Organization classifications [Arber, 2016] with an IPSS-R classification of very low, low, or intermediate risk disease, with an overall risk score ≤3.5 [Greenberg, 2012].
3. 3. Received ESA OR luspatercept and/or other therapies approved by health authorities and available for the treatment of LR-MDS-related anemia that is relapsed/refractory or intolerant to the most recent therapy prior to screening. −Relapse/Refractory to most recent prior treatment: documentation of loss of erythroid (E) response or never achieved hematologic improvement (HI-E) response as defined by the IWG 2018 criteria [Platzbecker, 2019]. If the most recent prior treatment is ESA or Luspatercept.
4. 4. Red blood cell transfusion dependence, defined as requiring an average of ≥4 units of pRBC transfused over an 8-week period during the 16 weeks preceding randomization. Documentation of a participant’s transfusion policy during this 16week period is required.
5. 5. 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) (as defined in Section 10.4), OR b. Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency (as described in Section 10.4) 28 days prior to and during the study intervention period and for at least 1 week after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
6. 6. Is capable of giving signed informed consent as described in Section 10.1, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
7. 7. Eastern Cooperative Oncology Group performance status ≤2 (see Section 10.7)
8. 8. Adequate organ function as defined in Table 8.

Exclusion criteria 20

1. Participants are excluded from the study if any of the following criteria apply. 1. Prior treatment with the following at any time: a. Hypomethylating agents or other disease modifying agents (i.e., IMiDs) and immunosuppressive therapy for MDS Note: Exception to this exclusion is if ≤1 week of treatment received; provided last dose was ≥8 weeks from randomization
2. 2. Use of the following treatments within the noted time periods referenced from date of randomization: a. ESA within 4 weeks, or 8 weeks for long-acting ESA b. Growth factors (i.e., G-CSF, GM-CSF) within 4 weeks c. Luspatercept within 8 weeks d. Imetelstat within 8 weeks e. Investigational agents within 4 weeks or 5 half-lives, whichever is longer f. 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 g. Other active anti-MDS therapy not otherwise listed within 28 days or 5 halflives whichever is longer h. Potent cytochrome P450 3A4 (CYP3A4) inducers, except for rifampin and rifampicin, within 14 days prior to the first dose of momelotinib i. Has received a live vaccine within 30 days
3. 3. Prior allogeneic or autologous stem cell transplant
4. 4. Has had any major surgery within 28 days prior to randomization
5. 5. 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.
6. 6. MDS associated with del 5q cytogenetic abnormality
7. 7. 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).
8. 8. Known history of diagnosis of acute myeloid leukemia.
9. 9. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, gastrointestinal bleeding, or thalassemia.
10. 10. Diagnosis of invasive malignancy or history of invasive malignancy other than the disease under study within the last 5 years, except as noted below: a. History of an invasive malignancy for which the participant was definitively treated, and in which the participant has been disease free for at least 2 years, and which, in the opinion of the principal investigator and medical monitor, is not expected to affect the evaluation of the effects of the study intervention on the currently targeted disease under study b. Curatively treated basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, and/or in situ breast cancer may be enrolled c. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM clinical staging system)
11. 11. Uncontrolled intercurrent illness including, but not limited to: a. Active uncontrolled infection (participants receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the trial); or b. Significant active or chronic bleeding event ≥Grade 2 per CTCAE v5.0 within 4 weeks prior randomization c. Uncontrolled acute and chronic liver disease (e.g., Child-Pugh score ≥10) OR has current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria
12. 12. Any of the following conditions within 6 months prior to randomization: a. Unstable angina pectoris b. Symptomatic congestive heart failure c. Uncontrolled cardiac arrhythmia
13. 13. QTc interval >480 msec (corrected using Fridericia formula).
14. 14. Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor.
15. 15. Presence of peripheral neuropathy ≥Grade 2 per CTCAE v5.0.
16. 16. Known positive status for HIV.
17. 17. Hepatitis A, B, or C status as defined below: a. Chronic active or acute viral hepatitis A. b. Active Hepatitis B infection indicated by the presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to the first dose of study intervention. c. Positive hepatitis C antibody test result at screening or within 3 months before the first dose of study intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained.
18. 18. Has any clinically significant gastrointestinal conditions or abnormalities that may alter absorption, e.g., uncontrolled nausea, vomiting, malabsorption syndrome or major resection of the stomach and/or bowels.
19. 19. Is unable to swallow and/or retain oral medications
20. 20. Known contraindication or hypersensitivity to momelotinib and its metabolites, or any of their excipients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Percentage of participants with RBC-TI (rolling 12 weeks)
2. 2. Selected safety endpoints: Grade >= 3 AE, AEs leading to treatment discontinuation and/or dose modifications
3. 3. Pharmacokinetic parameters of momelotinib and M21 (e.g., Cmax, AUC), as data permit

Secondary endpoints 4

1. 1. Percentage of participants with ≥12 weeks of RBC-TI by the end of Week 24
2. 2. Incidence and severity of AEs and SAEs, and AEs leading to treatment discontinuation or dose modifications by the end of Week 24 and longer term
3. 3. Clinically important changes in laboratory parameters and vital signs by the end of Week 24 and longer term
4. 4. Plasma concentration of momelotinib and M21

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 12

Locations

5 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications