AJ1-11095 for Myelofibrosis

Recruiting at 12 trial locations

Overseen By David Steensma, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ajax Therapeutics, Inc.

Must be taking: Type I JAK2 inhibitors

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: Splenectomy, Hepatitis B/C, Chemotherapy, others

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

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, AJ1-11095, to determine its safety and effectiveness for people with myelofibrosis, a condition where scar tissue forms in the bone marrow. The study will explore different doses to assess the drug's effects on the body and its potential to reduce symptoms. It targets individuals with myelofibrosis who have not achieved desired results from previous treatments. Participants should have noticeable symptoms, such as an enlarged spleen or persistent discomfort. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop using a JAK2 inhibitor 10 days before starting the study drug and chemotherapy 4 weeks prior. You can continue using Hydrea until 5 days before starting the trial. If you are on a strong CYP3A4 inhibitor, you cannot participate in the trial.

Is there any evidence suggesting that AJ1-11095 is likely to be safe for humans?

Research shows that AJ1-11095 is undergoing its first human trials, so information about its safety remains limited. As a type II JAK2 inhibitor, researchers are closely monitoring how well participants tolerate it.

In studies of similar drugs, researchers identify side effects to determine the highest safe dose. This information helps them adjust the dose to find the safest and most effective amount.

Since AJ1-11095 is in early testing stages, the primary goal is to understand potential side effects and how the body processes the drug. Prospective participants should know that researchers are closely monitoring safety and will adjust doses to ensure the best outcomes. ^{1 2 3 4 5}

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

Researchers are excited about AJ1-11095 for myelofibrosis because it offers a new approach compared to standard treatments like ruxolitinib or fedratinib, which mainly target JAK2 signaling. AJ1-11095 may have a novel mechanism of action that targets different pathways involved in myelofibrosis, potentially leading to improved outcomes. Additionally, AJ1-11095 is administered orally, which is convenient for patients and could enhance compliance. This drug is being explored in multiple dosing cohorts, which helps determine the most effective and safe dose for patients.

What evidence suggests that this trial's treatment, AJ1-11095, could be effective for myelofibrosis?

Research has shown that AJ1-11095, a new medication, has produced promising results in early studies for treating myelofibrosis, a bone marrow disorder. These studies suggest it might outperform current treatments. In this trial, participants will receive different doses of AJ1-11095 to evaluate its effectiveness. AJ1-11095 may improve bone marrow health, reduce harmful genetic changes in cells, and support normal blood production. These early findings offer hope for its effectiveness in managing the symptoms and progression of myelofibrosis. ^{3 5 6 7 8}

Who Is on the Research Team?

John Mascarenhas, M.D.

Principal Investigator

Mt. Sinai

Are You a Good Fit for This Trial?

This trial is for adults with primary or secondary myelofibrosis who didn't respond well to a previous treatment with a type I JAK2 inhibitor. Participants must have certain spleen sizes, symptom scores, and blood counts, as well as an adequate kidney function.

Inclusion Criteria

ANC ≥1.0×10^9/L

Platelet count ≥75×10^9/L

AST and ALT ≤3.0 × ULN

Exclusion Criteria

I have had my spleen removed.

I have not had radiation to my spleen in the last 3 months.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of AJ1-11095 to evaluate safety and establish the maximum tolerated dose (MTD)

24 weeks

Weekly visits for dose escalation

Dose Expansion

Participants receive the recommended phase 2 dose (RP2D) to gather additional safety and efficacy data

24 weeks

Bi-weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AJ1-11095

Trial Overview The study tests AJ1-11095, a new oral medication intended to inhibit JAK2 differently than prior treatments. It's in phase 1 where the focus is on assessing safety, how the body processes it (PK), and its effects on the disease (PD).

How Is the Trial Designed?

Group I: Dose Expansion Cohort 2 Experimental Treatment 1 Intervention

Alternative candidate RP2D of AJ1-11095 taken orally by patients.

Group II: Dose Expansion Cohort 1 Experimental Treatment 1 Intervention

Candidate RP2D of AJ1-11095 taken orally by patients.

Group III: Cohort 5 Experimental Treatment 1 Intervention

Dose E of AJ1-11095 taken orally by patients.

Group IV: Cohort 4 Experimental Treatment 1 Intervention

Dose D of AJ1-11095 taken orally by patients.

Group V: Cohort 3 Experimental Treatment 1 Intervention

Dose C of AJ1-11095 taken orally by patients.

Group VI: Cohort 2 Experimental Treatment 1 Intervention

Dose B of AJ1-11095 taken orally by patients.

Group VII: Cohort 1 Experimental Treatment 1 Intervention

Dose A of AJ1-11095 taken orally by patients.

Who Is Running the Clinical Trial?

Ajax Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

Myelofibrosis (MF) is primarily treated with JAK inhibitors, which help reduce spleen size and alleviate symptoms, but these treatments have limitations and are not suitable for all patients.

Emerging novel JAK inhibitors and combination therapies aim to address unmet needs in MF treatment, potentially offering deeper responses and improved long-term outcomes for a wider range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis. Kuykendall, AT., Komrokji, RS.[2022]

Ruxolitinib, the first FDA-approved treatment for myelofibrosis, significantly reduced spleen volume by ≥ 35% in 42% of patients compared to only 1% in the placebo group, demonstrating its efficacy in treating this condition.

While ruxolitinib effectively improved symptoms and spleen size, it was associated with increased risks of severe anemia, thrombocytopenia, and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Deisseroth, A., Kaminskas, E., Grillo, J., et al.[2022]

BAY 94-9027, an extended-half-life recombinant factor VIII product, demonstrated a significantly higher pharmacokinetic profile compared to rFVIIIFc, with a higher area under the curve (AUClast) indicating better drug exposure in patients with hemophilia A.

The study, involving 18 patients aged 18-65, found no adverse events, suggesting that BAY 94-9027 is safe for use, and it also showed a longer time to reach FVIII threshold levels, which may benefit patients needing sustained factor levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A. Shah, A., Solms, A., Wiegmann, S., et al.[2023]

In a phase 2 trial involving 118 patients with myelofibrosis, jaktinib demonstrated significant efficacy, with 54.8% of patients on the 100 mg BID dosage achieving a ≥35% reduction in spleen volume at week 24, compared to 31.3% in the 200 mg QD group.

Jaktinib also improved hemoglobin levels in 35.6% of patients with low baseline hemoglobin and resulted in a ≥50% improvement in total symptom scores for 69.6% of patients in the BID group, indicating its potential as a well-tolerated treatment option for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naïve patients with myelofibrosis: Results of a phase II trial. Zhang, Y., Zhou, H., Jiang, Z., et al.[2023]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a randomized trial involving six hemophiliacs and 207 bleeding episodes, a minimum effective dose of 5.7 units/kg of factor-VIII concentrate successfully controlled 85% of spontaneous joint bleeds.

Using a lower dose of 3.0 units/kg significantly increased the risk of treatment failure, indicating that this dose is only suitable for mild bleeds as perceived by the patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimum effective dose of intermediate factor-VIII concentrate in haemophiliacs on home therapy. Stirling, ML., Prescott, RJ.[2019]

Ruxolitinib, a JAK1/2 inhibitor, is currently the only approved treatment for myelofibrosis, effectively reducing spleen size and improving symptoms, but it has limitations such as myelosuppression and the development of drug resistance.

Research is ongoing to identify new therapeutic targets for myelofibrosis, including JAK1, JAK2, and other related pathways, which may lead to more effective treatments and address the challenges posed by current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapies for Myelofibrosis. Pettit, K., Odenike, O.[2023]

BAY 94-9027 (damoctocog alfa pegol) demonstrated long-term safety in previously treated pediatric patients with severe hemophilia A, with no development of FVIII inhibitors or anti-PEG antibodies over a median treatment duration of 5 years.

The treatment significantly reduced the annualized bleeding rate (ABR), with a median ABR of 1.5 for patients under 6 years and 1.9 for those aged 6-12 years, and a spontaneous ABR of 0.0 in the last year of treatment, indicating effective bleed prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A. Mancuso, ME., Biss, T., Fischer, K., et al.[2021]

Rurioctocog alfa pegol (BAX 855) shows an extended half-life and good tolerability in patients with severe hemophilia A, with a significantly lower annualized bleeding rate in those receiving prophylactic treatment compared to on-demand treatment, based on a study of 137 patients.

The Japanese subpopulation demonstrated similar pharmacokinetic, safety, and efficacy profiles to the overall population, with no reported cases of FVIII inhibition or anaphylactic reactions, indicating that BAX 855 is a safe and effective treatment option across different populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of full-length pegylated recombinant factor VIII with extended half-life in previously treated patients with hemophilia A: comparison of data between the general and Japanese study populations. Nogami, K., Shima, M., Fukutake, K., et al.[2021]

BAY 94-9027 demonstrated effective bleed prevention in children with severe hemophilia A, with a median annualized bleeding rate of 2.9 in the first part of the study and 2.4 in the second part, indicating its efficacy across different age groups.

No patients developed FVIII inhibitors during the study, suggesting a favorable safety profile, although 12 patients discontinued treatment due to loss of efficacy or hypersensitivity, primarily in the younger cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PROTECT VIII Kids: BAY 94-9027 (PEGylated Recombinant Factor VIII) safety and efficacy in previously treated children with severe haemophilia A. Santagostino, E., Kenet, G., Fischer, K., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06343805?cond=Myotonia%20fluctuans%20OR%20%22exercise-induced%20delayed-onset%20myotonia%22%20OR%20%22%20Fluctuating%20myotonia%22%20OR%20%22%20MF%22&aggFilters=status:not%20rec&viewType=Table&rank=8

NCT06343805 | A Phase 1 Study of AJ1-11095 in Patients ... AJX-101 is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, ...

2. onclive.com onclive.com/view/type-ii-jak-inhibitor-aj1-11095-under-phase-1-investigation-in-myelofibrosis

Type II JAK Inhibitor AJ1-11095 Under Phase 1 ... - OncLive A phase 1 study (NCT06343805) will investigate the safety and efficacy of treatment with AJ1-11095 in patients with primary myelofibrosis, ...

3. targetedonc.com targetedonc.com/view/phase-1-study-of-type-ii-jak2-inhibitor-in-myelofibrosis-enrolls-first-patient

Phase 1 Study of Type II JAK2 Inhibitor in Myelofibrosis ... In preclinical studies, AJ1-11095 showed improved efficacy compared with type I JAK2 inhibitors and showed significant disease-modifying ...

4. ajaxtherapeutics.com ajaxtherapeutics.com/wp-content/uploads/2024/12/Ajax-Therapeutics-Abstract-3147-1-AJX-101-ASH-2024-TIPS-final.pdf

A Multicenter, Open-Label, Phase 1 Clinical Trial of AJ1- ... Myelofibrosis (MF) is a chronic hematologic malignancy with substantial symptom burden, splenomegaly, anemia, and reduced overall survival.

5. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/ajax-presents-phase-1-trial-results-for-myelofibrosis-treatment/

Ajax Presents Phase 1 Trial Results for Myelofibrosis ... Preclinical studies suggest AJ1-11095 may offer benefits such as reversing bone marrow fibrosis, reducing mutant allele burden, and maintaining ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06343805

NCT06343805 | A Phase 1 Study of AJ1-11095 in Patients ... The candidate RP2D will be based on AE pattern, PK and biomarker information, in addition to all available safety and efficacy data. Expansion cohorts will ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3147.1/529073/A-Multicenter-Open-Label-Phase-1-Clinical-Trial-of

A Multicenter, Open-Label, Phase 1 Clinical Trial of AJ1 ... AJ1-11095 is a novel orally bioavailable small molecule type II non ... safety/tolerability and pharmacokinetics data. Dose limiting ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093911

A Multicenter, Open-Label, Phase 1 Clinical Trial of AJ1- ... AJ1-11095 is a novel orally bioavailable small molecule type II non ... safety/tolerability and pharmacokinetics data. Dose limiting toxicities ...