JNJ-88549968 for Myeloproliferative Disorder

Recruiting at 33 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Recent malignancies, Organ transplant, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

100 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 determine the optimal dose of a new treatment called JNJ-88549968, an experimental therapy. It targets individuals with specific blood disorders, such as essential thrombocythemia or myelofibrosis, particularly those with a CALR gene mutation. The study begins by gradually increasing the dose to identify the right amount, then continues with the optimal dose to assess its effectiveness and safety. Individuals with these conditions that affect daily life may find this trial suitable. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that JNJ-88549968 is likely to be safe for humans?

Research has shown that JNJ-88549968 is a treatment for certain blood disorders. This new drug is designed to help the immune system target cancer cells. As this is the first time it is being tested in humans, detailed safety information is limited. The trial is in its early stages, with the main goal of determining the drug's safety and the optimal dose for future studies.

Early-stage trials like this one focus on safety. Researchers closely monitor participants' reactions to the treatment and any side effects. The trial's progression suggests initial tests have shown some safety. This is just the beginning of the research, and more information will become available as the study continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for myeloproliferative disorders, which often focus on managing symptoms or slowing disease progression, JNJ-88549968 is unique because it targets the underlying mechanisms of the disease. Researchers are excited about this treatment because it involves a new active ingredient designed to modify disease activity at a molecular level, potentially offering a more precise intervention. This approach could lead to improved outcomes by directly addressing the root causes rather than just alleviating symptoms.

What evidence suggests that JNJ-88549968 might be an effective treatment for myeloproliferative disorder?

Research has shown that JNJ-88549968 delivers promising results in lab studies. The treatment effectively killed cancer cells with specific changes, known as CALR mutations, found in certain blood disorders. These results appeared across various CALR mutations, suggesting broad potential. Additionally, similar early-stage treatments for these blood disorders have often progressed successfully to later development stages. Although human study data remains limited, these early signs offer hope for its effectiveness. Participants in this trial will receive JNJ-88549968 in a dose escalation phase to determine the optimal dosing schedule, followed by a dose expansion phase at the recommended phase 2 dose. ^{1 3 4 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with a specific mutation called CALR in their blood cells, leading to conditions like thrombocytosis and myelofibrosis. They should be able to perform daily activities with ease or only have slight limitations (ECOG <=2). The study excludes details not provided.

Inclusion Criteria

I am at least 18 years old or the legal age of majority where the study is conducted.

My blood disorder is due to a specific CALR mutation.

I can take care of myself and am up and about more than half of my waking hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-88549968 with dose escalation to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule based on safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy

Approximately 5 weeks

Multiple visits (in-person)

Dose Expansion

Participants receive JNJ-88549968 at the RP2D regimen determined in dose escalation

Up to 2 years

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• JNJ-88549968

Trial Overview The trial tests JNJ-88549968's safety and the best dose for treating certain blood disorders. It has two parts: finding the right dose (Dose Escalation) and then seeing how safe it is at that dose (Cohort Expansion).

How Is the Trial Designed?

Group I: Dose Escalation (Part 1) and Dose Expansion (Part 2) Experimental Treatment 1 Intervention

In dose escalation (Part 1), participants will receive JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule(s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. In dose expansion (Part 2), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1).

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

JAK inhibitors, particularly ruxolitinib, have become essential in treating classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) like primary myelofibrosis (PMF) and polycythemia vera (PV), showing significant efficacy over the past several years.

Newer JAK inhibitors, such as pacritinib and Itacitinib, are being explored for their potential benefits, including reduced side effects and improved treatment outcomes, particularly in managing anemia associated with myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium. Griesshammer, M., Sadjadian, P.[2021]

The JAK2 V617F mutation is commonly found in patients with myeloproliferative neoplasms and leukemias, making Janus kinases important targets for new cancer therapies.

Ruxolitinib (Jakafi®) is the first approved JAK inhibitor that effectively targets JAK2 V617F signaling, and the review discusses potential combination therapies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms. Gäbler, K., Behrmann, I., Haan, C.[2023]

INCB018424, a JAK2 inhibitor, has shown significant clinical activity in treating myelofibrosis (MF), leading to rapid reductions in spleen size and improvements in symptoms for patients taking 10-25 mg twice daily.

The treatment was generally well tolerated, with reversible thrombocytopenia occurring in 30% of patients at the higher dose, while it was not observed at the lower dose, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK2 inhibitors: A reality? A hope? Apostolidou, E., Kantarjian, HM., Verstovsek, S.[2023]

Crizotinib effectively suppresses the proliferation of cells and JAK/STAT signaling in myeloproliferative neoplasms (MPN), showing preclinical efficacy in patient samples and mouse models with JAK2 mutations.

The combination of crizotinib with JAK inhibitors like ruxolitinib can overcome resistance to treatment, suggesting that crizotinib may be a promising option for patients with MPN who experience persistence with JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms. Gurska, LM., Okabe, R., Schurer, A., et al.[2023]

The study analyzed 60 cases of myeloproliferative neoplasms (MPN) with both JAK2 V617F and BCR-ABL mutations, highlighting that these mutations can coexist, particularly in patients with chronic myelogenous leukemia (CML).

It was found that polycythemia vera (PV) was the most common type of MPN associated with these mutations, emphasizing the importance of simultaneous testing for both mutations to ensure accurate diagnosis and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of Clinical Characteristics of JAK2 V617F and BCR-ABL Double-Mutant Myeloproliferative Neoplasms]. Yan, J., Ding, YW., Wang, PY., et al.[2022]

Ruxolitinib (RUX), a JAK2 inhibitor, has shown significant efficacy in treating myelofibrosis (MF) and polycythemia vera (PV), achieving a spleen volume response in over 60% of advanced MF patients and hematocrit control in about 60% of PV cases.

While RUX is effective with mild toxicity, long-term treatment may lead to a loss of spleen volume response in MF patients, and monitoring for side effects like decreased hemoglobin/platelet levels and skin tumors is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of JAK2 inhibitors in MPNs 7 years after approval. Passamonti, F., Maffioli, M.[2021]

In a study of 1811 patients with myeloproliferative neoplasms (MPNs), the JAK2 p.V617F mutation was found in 96.7% of those with JAK2 mutations, confirming its status as the most common mutation associated with these conditions.

The study also identified several non-p.V617F JAK2 mutations in a small percentage of patients, indicating the presence of genetic diversity in MPNs that may have implications for diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. Alghasham, N., Alnouri, Y., Abalkhail, H., et al.[2016]

ZT55 is a highly selective inhibitor of the JAK2V617F mutation, showing a potent effect with an IC50 value of 0.031 μM, which leads to significant inhibition of the JAK-STAT signaling pathway.

In both in vitro and in vivo studies, ZT55 effectively induced apoptosis in JAK2V617F-expressing cells and suppressed tumor growth, demonstrating its potential as a therapeutic option for myeloproliferative neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2V617F against myeloproliferative neoplasms. Hu, M., Xu, C., Yang, C., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06150157

A Study of JNJ-88549968 for the Treatment of Calreticulin ... The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968, ...

2. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/jnj-88549968-johnson-johnson-myeloproliferative-disorders-likelihood-of-approval/

JNJ-88549968 by Johnson & Johnson for ... According to GlobalData, Phase I drugs for Myeloproliferative Disorders have an 83% phase transition success rate (PTSR) indication benchmark ...

3. isrctn.com isrctn.com/ISRCTN79300015

A study of JNJ-88549968 for the treatment of calreticulin ... To evaluate effectiveness of drug JNJ-88549968 in participants with diseases essential thrombocythemia (ET) in which the bone marrow produces too many platelets ...

4. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper173430.html

Paper: Discovery of JNJ-88549968, a Novel, First-in-Class ... JNJ-88549968-mediated cytotoxicity was observed against all tested CALRmut CD34+ cancer cells and was independent of the type of CALR mutation.

5. clinicaltrials.jnj.com clinicaltrials.jnj.com/en/study-detail/NCT06150157?

J&J Study NCT06150157 - J&J Clinical Trials The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968, ...

6. synapse.patsnap.com synapse.patsnap.com/drug/3966ded2a80546448b97383d862be23a

JNJ-88549968 - Drug Targets, Indications, Patents A first-in-human study of the safety, pharmacokinetics, and pharmacodynamics of JNJ-88549968, a T-cell redirecting bispecific antibody for CALR-mutated ...