DISC-0974 for Myelofibrosis

Recruiting at 14 trial locations

Overseen By Disc Medicine Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Disc Medicine, Inc

Must be taking: JAK inhibitors

Must not be taking: Iron chelation

Disqualifiers: Hereditary hemochromatosis, Hemoglobinopathy, others

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

Compensation: Varies

Number of Visits: 7

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called DISC-0974 in people with myelofibrosis or myelodysplastic syndrome who also have anemia. Researchers seek to determine how well the drug alleviates anemia and its overall impact on participants. The treatment will be administered as an injection under the skin every four weeks. This trial may suit individuals with anemia and myelofibrosis or myelodysplastic syndrome who regularly need blood transfusions or have low hemoglobin levels, which is the part of blood that carries oxygen. As a Phase 1, Phase 2 trial, it 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. There is a required washout period (time without taking certain medications) of at least 28 days for specific treatments like androgens, erythropoietin, and others. If you are on JAK inhibitors or hydroxyurea, a 60-day washout period is needed if you discontinue them before screening.

Is there any evidence suggesting that DISC-0974 is likely to be safe for humans?

Research has shown that DISC-0974 is generally safe and well-tolerated. In studies where patients received it as a monthly injection under the skin, all tested doses were well-managed. No serious safety issues arose. This treatment also positively affected anemia, a condition characterized by fewer healthy red blood cells. It lowered hepcidin, a protein that can affect iron levels, and helped improve anemia symptoms. Overall, the evidence suggests that DISC-0974 is safe for use in these studies. ^{1 2 3 4 5}

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

Unlike standard treatments for myelofibrosis, which often focus on managing symptoms with medications like JAK inhibitors, DISC-0974 works differently by targeting hepcidin regulation. Hepcidin is a key hormone involved in iron metabolism, and by modulating its levels, DISC-0974 aims to address anemia, a common challenge in myelofibrosis patients. This novel mechanism of action offers a fresh approach that could potentially improve treatment outcomes and enhance quality of life for patients. Researchers are excited about the potential of DISC-0974 to provide a more effective and targeted treatment option for myelofibrosis.

What evidence suggests that DISC-0974 might be an effective treatment for myelofibrosis?

Research has shown that DISC-0974, which participants in this trial will receive, may help treat anemia in people with myelofibrosis. Studies have found that DISC-0974 lowers hepcidin, a protein that affects iron levels in the body. Lowering hepcidin can increase iron levels, which is important for making healthy red blood cells. In earlier studies, about 50% of patients experienced major improvements in their blood counts. This suggests that DISC-0974 could help reduce anemia symptoms in people with myelofibrosis. ^{1 2 4 6 7}

Who Is on the Research Team?

Will Savage, MD PhD

Principal Investigator

Disc Medicine

Are You a Good Fit for This Trial?

Adults over 18 with myelofibrosis and anemia can join this trial. They should have a certain level of disease severity, be able to perform daily activities, and have kidneys that work well enough. Participants need to stop some treatments before joining and meet specific blood count criteria. People who've had recent major surgery or other cancers (with exceptions), active infections, or severe heart problems cannot join.

Inclusion Criteria

I can take care of myself and perform daily activities.

My bone marrow biopsy shows I have a high-risk form of myelofibrosis.

I am not expected to have a stem cell transplant within the next 8 months.

Exclusion Criteria

I do not have severe allergies, heart issues, active Hepatitis B or C, or uncontrolled HIV.

Laboratory Exclusions like peripheral blood myeloblasts, positive direct antiglobulin test

I haven't had recent iron removal treatment or changed my blood thinner regimen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b: Dose Escalation

DISC-0974 is administered subcutaneously every 4 weeks to assess safety, tolerability, pharmacokinetics, and pharmacodynamics

8-12 weeks

3 visits (in-person)

Phase 2: Expansion

DISC-0974 is administered subcutaneously every 4 weeks to evaluate effects on anemia response

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DISC-0974

Trial Overview The study is testing DISC-0974's safety and how it affects the body in patients with myelofibrosis-related anemia. It's an early-stage trial where everyone gets the drug; there are no comparison groups.

How Is the Trial Designed?

Group I: Phase 2: Expansion Experimental Treatment 1 Intervention

In the Phase 2 (expansion) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.

Group II: Phase 1b: Dose Escalation Experimental Treatment 1 Intervention

In the Phase 1b (dose-escalation) portion of the study, DISC-0974 will be administered subcutaneously every 4 weeks.

Who Is Running the Clinical Trial?

Disc Medicine, Inc

Lead Sponsor

Trials

6

Recruited

580+

Published Research Related to This Trial

In a study comparing 100 patients with primary myelofibrosis (PMF) treated with ruxolitinib to 350 patients from the dynamic IPSS (DIPSS) study, those receiving ruxolitinib had a significantly longer survival time of 5 years compared to 3.5 years for the DIPSS cohort.

The analysis indicated that ruxolitinib may alter the natural progression of PMF, with a hazard ratio of 0.61 suggesting a 39% reduction in the risk of death compared to the DIPSS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts. Passamonti, F., Maffioli, M., Cervantes, F., et al.[2021]

In a study of 172 patients with primary myelofibrosis, several time-dependent factors were identified as significant predictors of death and blast phase (BP) progression, including the onset of anemia, leukocytosis, and thrombocytopenia.

Leukocytosis was particularly notable, as its occurrence during follow-up was linked to a higher risk of BP, suggesting that patients with this condition should be closely monitored to better assess disease severity and inform treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification during the follow-up of time-dependent prognostic factors for the competing risks of death and blast phase in primary myelofibrosis: a study of 172 patients. Morel, P., Duhamel, A., Hivert, B., et al.[2021]

In a study of 205 patients with lower-risk myelofibrosis (MF), it was found that over half had low hemoglobin and hematocrit levels, indicating significant blood-related issues, and nearly all patients had comorbid conditions, with hypertension being the most common.

At the time of enrollment, 55.6% of patients were on MF-directed treatment, primarily hydroxyurea and ruxolitinib, highlighting the common treatment patterns for managing lower-risk MF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Myelofibrosis Enrolled in the MOST Study. Gerds, AT., Lyons, RM., Colucci, P., et al.[2022]

A study of 802 patients with primary myelofibrosis (PMF) showed that those diagnosed between 1996 and 2007 had a median survival of 6.5 years, compared to 4.6 years for those diagnosed from 1980 to 1995, indicating a significant improvement in survival rates over time.

Patients diagnosed more recently also exhibited fewer severe symptoms, such as marked anemia and high leukocyte counts, suggesting that while overall survival has improved, those in high-risk categories still face challenges that need to be addressed with new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving survival trends in primary myelofibrosis: an international study. Cervantes, F., Dupriez, B., Passamonti, F., et al.[2012]

In a study of 270 Chinese patients with myelofibrosis (MF), the median overall survival for primary MF was 66 months, with age over 65, low platelet count, and leukemic transformation identified as significant negative prognostic factors.

The study found that unfavorable karyotypes and circulating blasts greater than 1% were also associated with poorer leukemia-free survival, indicating that these factors could help predict outcomes in MF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic features and prognostic indicators in Chinese patients with myelofibrosis. Gill, H., Leung, AY., Chan, CC., et al.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/657/530242/A-Phase-1b-Study-of-DISC-0974-an-Anti-Hemojuvelin

A Phase 1b Study of DISC-0974, an Anti-Hemojuvelin ... Treatment with DISC-0974 resulted in meaningful and sustained hepcidin reductions with mean change from baseline (mean 88.2 ng/mL; range [8.7, ...

2. ir.discmedicine.com ir.discmedicine.com/news-releases/news-release-details/disc-medicine-presents-positive-updated-results-phase-1b-trial

News Release Details Treatment with DISC-0974 results in substantial reductions in hepcidin and increases in iron levels translating to positive impact on clinically meaningful ...

3. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)02138-X/fulltext

MPN-757: A Phase 1b Trial of DISC-0974, an Anti- ... Major hematologic responses were achieved in 50% of non-TD participants, with overall response of 59%. All TD-Low and 60% of TD-High participants had ≥50% ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124034049

A Phase 1b Study of DISC-0974, an Anti-Hemojuvelin ... Hepcidin, a central regulator of iron homeostasis, is pathologically elevated in patients with myelofibrosis (MF) and anemia. Chronic hepcidin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05320198

NCT05320198 | Study of DISC-0974 (RALLY-MF) in ... This phase 1b/2a open-label study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of DISC-0974 as well as categorize the effects ...

6. discmedicine.com discmedicine.com/wp-content/uploads/2024/06/P1059_Gangat_final_5.24.2024.pdf

A Phase 1b Trial of DISC-0974 in Patients with ... DISC-0974 demonstrated acceptable safety and tolerability at all evaluated dose levels. • DISC-0974 dosing resulted in decreased hepcidin and increased ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20536443

Study Of DISC-0974 In Participants With Myelofibrosis Or ... This phase 1b/2a open-label study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of DISC-0974 as well as categorize the effects on ...