DFV890 for Myeloid Diseases

Recruiting at 32 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: NLRP3 inhibitors, IL-1 inhibitors, CYP modulators

Disqualifiers: Antineoplastic therapy, Hypersensitivity, others

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

Compensation: Varies

Number of Visits: 9

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, DFV890, to assess its safety and effectiveness for people with certain myeloid diseases. It targets patients with lower-risk myelodysplastic syndromes (MDS), lower-risk chronic myelomonocytic leukemia (CMML), and high-risk clonal cytopenia of undetermined significance (HR CCUS). The study tests different doses of DFV890 to identify the optimal one. Individuals with these conditions who have not responded well to other treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take certain cancer treatments, experimental therapies, or medications that affect specific liver enzymes (CYP2C9 and CYP3A) close to the start of the study. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that DFV890 is likely to be safe for humans?

Research has shown that DFV890 is generally safe. In earlier studies, patients with low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) tolerated DFV890 well. No deaths or serious side effects required urgent medical attention. DFV890 was tested at different doses, and although the body's exposure to the drug increased, it did not directly correlate with the dose size. This suggests that even at higher doses, side effects did not worsen. Overall, DFV890 appears well-tolerated, which is promising for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about DFV890 for myeloid diseases because it offers a potentially novel approach in treatment compared to existing options like chemotherapy and targeted therapies. DFV890 is distinctive as it targets inflammation pathways specifically linked to myeloid diseases, which might lead to more effective management of symptoms and disease progression. Unlike traditional treatments, which often have broad effects and can impact healthy cells, DFV890 aims to minimize side effects by honing in on key pathways involved in the disease. This targeted action could make DFV890 a promising option for patients with fewer side effects and improved outcomes.

What evidence suggests that DFV890 might be an effective treatment for myeloid diseases?

Research has shown that DFV890 is a promising treatment for myeloid diseases. DFV890 blocks certain proteins that cause inflammation and cell damage, common issues in myeloid diseases. This trial will explore various dosages of DFV890, including low and high doses, to assess its effectiveness. Early studies demonstrated that DFV890 can reduce harmful inflammation and support better blood health in patients. These findings suggest that DFV890 may help by calming inflammation and supporting normal blood cell growth. ^{4 5 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with certain low-risk myeloid diseases (like MDS or CMML) who haven't responded well to other treatments can join. They must be able to have bone marrow tests and have a performance status indicating they can still do daily activities. People who've had recent cancer treatments, are sensitive to DFV890 or similar drugs, or take certain other medications cannot participate.

Inclusion Criteria

Patients must have one of the following for eligibility into the study:

My CMML is low to intermediate risk and didn't respond well to hydroxyurea or HMAs.

I am willing and able to have bone marrow tests as per my hospital's rules.

Exclusion Criteria

History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes

I have not taken medications like DFV890 that target specific inflammation pathways.

I haven't used any blood cell growth boosters in the last week or longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Optimization

Participants receive DFV890 at varying doses to determine the optimal dose for safety and efficacy

24 weeks

6 cycles of treatment

Dose Expansion

Participants receive the optimized dose of DFV890 to further assess safety and efficacy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• DFV890

Trial Overview The trial is testing DFV890's safety and effectiveness for myeloid diseases in two parts: one part tries different doses to find the best one, and the second part gives that dose to more people. It looks at how the drug works in the body and its impact on disease symptoms.

How Is the Trial Designed?

Group I: Dose expansion: DFV890 low dose Experimental Treatment 1 Intervention

DFV890 given as single agent at a low dose

Group II: Dose escalation: DFV890 low dose Experimental Treatment 1 Intervention

DFV890 given as single agent at a low dose

Group III: Dose escalation: DFV890 high dose Experimental Treatment 1 Intervention

DFV890 given as single agent at a high dose

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3250/498948/Safety-and-Preliminary-Efficacy-of-DFV890-in-Adult

Safety and Preliminary Efficacy of DFV890 in Adult Patients ... DFV890, a small molecule NLRP3 inhibitor, blocks IL-1β and IL-18 secretion and pyroptotic cell death in response to a wide variety of NLRP3-dependent danger ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05552469

Dose Optimization and Expansion Study of DFV890 in ... The study seeks to determine the optimal dose of DFV890 that is safe and efficacious in patients with myeloid disease. The effectiveness and safety/tolerability ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S000649712309852X

Safety and Preliminary Efficacy of DFV890 in Adult Patients ... DFV890 may disrupt the smoldering inflammation and provide disease-modifying benefits to pts by improving hematopoiesis.

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper198326.html

Preliminary Safety and Biomarker Results of the NLRP3 ... DFV890 may disrupt the smoldering inflammation and provide disease-modifying benefits to patients by restoring normal hematopoiesis and suppressing clonal ...

5. sparkcures.com sparkcures.com/trial/1752/NCT05552469

Multiple Myeloma Support + Trials Researchers want to find the best dose of DFV890 to use in people with myeloid diseases. Myeloid diseases include myelodysplastic syndrome (MDS) and chronic ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/353/530770/Preliminary-Safety-and-Biomarker-Results-of-the

Preliminary Safety and Biomarker Results of the NLRP3 ... This open-label, phase 1b, multicenter study evaluates DFV890 in patients with very low, low, or intermediate risk MDS per revised International ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124031008

Preliminary Safety and Biomarker Results of the NLRP3 ... Preliminary findings from this ongoing study show a favorable safety profile in patients with LR-MDS and LR-CMML, in line with prior human studies with DFV890.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11101992/

First‐in‐human safety, tolerability, and pharmacokinetic ... DFV890 was generally well‐tolerated. Neither deaths nor serious adverse events were reported. A less than dose‐proportional increase in exposure ...