INCB000928 for Myelodysplastic Syndrome

(LIMBER Trial)

No longer recruiting at 20 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Incyte Corporation

Must not be taking: ESAs, Immunomodulatory drugs

Disqualifiers: Stem cell transplant, Major surgery, Cardiac disease, Chronic liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately up to 7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called INCB000928 (also known as Zilurgisertib) for individuals with Myelodysplastic Syndromes (MDS) or Multiple Myeloma (MM) who require regular blood transfusions or have anemia (low red blood cell count). Researchers seek to determine the safety and effectiveness of this treatment when used alone. The study is open to those with MDS who haven't responded to other anemia treatments and those with MM who have tried standard treatments without success. Participants should experience symptoms that affect daily life, such as frequent fatigue due to anemia. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications before joining the trial. Specifically, you cannot have had chemotherapy, immunomodulatory drugs, or other specified treatments within 28 days or 5 half-lives before starting the study drug. Also, you cannot be on certain other medications like strong CYP3A4/5 inhibitors or inducers during the study.

Is there any evidence suggesting that INCB000928 is likely to be safe for humans?

Research has shown that INCB000928, also known as zilurgisertib, is being tested for safety in people with myelodysplastic syndrome (MDS) and multiple myeloma (MM). Early results suggest that the treatment is generally well-tolerated. Recent studies have focused on safety, with researchers closely monitoring how the body processes the drug and any side effects. While detailed safety information is still being collected, ongoing research supports further development of INCB000928. Participants in earlier studies reported no major side effects, indicating a promising safety profile so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelodysplastic syndrome?

Unlike the standard treatments for Myelodysplastic Syndrome (MDS), which often focus on managing symptoms or supporting blood production, INCB000928 is unique because it targets the underlying causes of anemia in patients who are transfusion-dependent. This drug works by addressing the specific pathways involved in the production of red blood cells, potentially reducing the need for blood transfusions. Researchers are excited about INCB000928 because it represents a new approach to treating MDS, offering hope for better management of anemia and improving patients' quality of life.

What evidence suggests that INCB000928 might be an effective treatment for Myelodysplastic Syndrome?

Research has shown that INCB000928 is being tested in this trial to assist people with myelodysplastic syndrome (MDS) and multiple myeloma (MM) who have anemia. Early results suggest that INCB000928 might alleviate anemia, a common issue in these conditions. The treatment targets specific processes involved in blood cell production. Initial studies examined its effectiveness in reducing the need for blood transfusions in patients. Although further research is necessary, this trial aims to confirm its ability to improve blood counts and reduce anemia symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Ekatarine Asatiani, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for adults with Myelodysplastic Syndromes (MDS) or Multiple Myeloma (MM) who need regular blood transfusions or have anemia symptoms. MDS patients must have tried other anemia treatments without success and can't be on certain therapies. MM patients should have already tried standard treatments without success. Participants must not be pregnant, planning to become pregnant, or father a child.

Inclusion Criteria

Agreement to avoid pregnancy or fathering children

I have MDS and only use hydroxyurea for treatment.

I need regular blood transfusions or have symptoms of anemia.

Exclusion Criteria

I haven't taken any blood cell-boosting drugs in the last 28 days.

I have a serious heart condition that is not under control.

You have had or currently have a significant heart rhythm problem as determined by the study doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INCB000928 as monotherapy to evaluate safety, tolerability, PK, PD, and efficacy

Approximately up to 7 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• INCB000928

Trial Overview The study tests INCB000928's safety and how well it works as a single therapy in people with MDS or MM who are dependent on transfusions or suffer from symptomatic anemia. It's a Phase 1/2 trial where researchers will also look at how the body processes the drug and its effects on the disease.

How Is the Trial Designed?

Group I: INCB000928 Experimental Treatment 1 Intervention

INCB000928 will be administered in participants with MDS or MM who are transfusion-dependent or present with symptomatic anemia.

INCB000928 is already approved in United States for the following indications:

Approved in United States as Zilurgisertib for:

• Fibrodysplasia ossificans progressiva (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

Several new therapeutic agents are being developed for myelodysplastic syndromes (MDS), including clofarabine, ezatiostat, tipifarnib, laromustine, and histone deacetylase inhibitors, each with different mechanisms of action.

Despite the challenges of MDS, which often leads to complications within 3 to 5 years of diagnosis, the ongoing clinical trials suggest that new treatment options may become available in the next 5 to 10 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for myelodysplastic syndromes. Steensma, DP.[2018]

Myelodysplastic syndrome (MDS) is a complex blood disorder with a significant risk of progressing to acute myeloid leukemia (AML) and currently lacks a proven curative treatment.

Emerging biological therapies that target both the cancerous blood cells and their surrounding environment show promise in overcoming resistance to existing treatments and may improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New options in the treatment of myelodysplastic syndrome. Grudeva-Popova, J.[2007]

Citations

1. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.7017

Phase 1/2 study of the activin receptor-like kinase (ALK) The primary endpoint is safety and tolerability. Secondary endpoints include efficacy (per anemia response parameters), pharmacokinetics, and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04582539?cond=multiple+myeloma&aggFilters=status%3A%2Cphase%3A

NCT04582539 | To Assess the Safety and Tolerability of ... This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 ...

3. library.ehaweb.org library.ehaweb.org/eha/2021/eha2021-virtual-congress/324301/jean-marie.michot.a.phase.1.2.open-label.multicenter.study.of.incb000928.html?f=listing%3D3%2Abrowseby%3D8%2Asortby%3D1%2Amedia%3D1

A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY OF ... The primary objective is to evaluate the safety and tolerability of INCB000928 monotherapy in pts with MDS or MM who present with transfusion- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431260/

P1022: PHASE 1/2 STUDY OF THE ACTIVIN RECEPTOR ... The primary endpoint is safety and tolerability. Secondary endpoints include efficacy (per anemia response parameters), pharmacokinetics, and pharmacodynamics ( ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/39/NCT04582539/SAP_001.pdf

INCB 00928-105 Statistical Analysis Plan Am 1 29 AUG 2024 To determine the efficacy of INCB000928 in participants with MDS or MM. For both MDS and MM disease groups: • For transfusion-independent ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7017

2 inhibitor zilurgisertib (INCB000928, LIMBER-104) as ... The primary endpoint is safety and tolerability. Secondary endpoints include efficacy (per anemia response parameters), pharmacokinetics, and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11802711/

Pharmacokinetics of Zilurgisertib With and Without Food from ... These pharmacokinetic and safety data support further clinical development of zilurgisertib, which is being studied for the treatment of patients with FOP ...

8. withpower.com withpower.com/trial/phase-2-preleukemia-7-2021-17f7f

INCB000928 for Myelodysplastic Syndrome (LIMBER Trial) This trial tests a new drug, INCB000928, for patients with MDS or MM who need regular blood transfusions or have severe anemia.

9. medchemexpress.com medchemexpress.com/zilurgisertib.html?srsltid=AfmBOoqcNo6ZVgx0rcmrR0w5TOE4-Y3t_DbMbPOrDcTWRUIWIr5wrnoN

Zilurgisertib (INCB-000928) | ALK2 Inhibitor Zilurgisertib (INCB-000928; NBU-928) is a selective ALK2 inhibitor with an IC50 value of 15 nM. Zilurgisertib inhibits SMAD1/5 phosphorylation with an IC50 ...