AJ1-11095 for Myelofibrosis
Recruiting in Palo Alto (17 mi)
+11 other locations
Overseen byJohn Mascarenhas, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
Trial Summary
What is the purpose of this trial?AJX-101 is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), clinical activity and changes in biomarkers of an orally administered type II JAK2 inhibitor, AJ1-11095, in subjects with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.
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.
What data supports the effectiveness of the drug AJ1-11095 for treating myelofibrosis?
While there is no direct data on AJ1-11095, similar drugs like jaktinib and ruxolitinib, which are also JAK inhibitors, have shown effectiveness in reducing spleen size and improving symptoms in myelofibrosis patients.
12345Eligibility Criteria
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
+10 more
Exclusion Criteria
I have had my spleen removed.
I have not had radiation to my spleen in the last 3 months.
Pregnant or breastfeeding
+9 more
Trial Timeline
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
Participant Groups
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).
7Treatment groups
Experimental Treatment
Group I: Dose Expansion Cohort 2Experimental Treatment1 Intervention
Alternative candidate RP2D of AJ1-11095 taken orally by patients.
Group II: Dose Expansion Cohort 1Experimental Treatment1 Intervention
Candidate RP2D of AJ1-11095 taken orally by patients.
Group III: Cohort 5Experimental Treatment1 Intervention
Dose E of AJ1-11095 taken orally by patients.
Group IV: Cohort 4Experimental Treatment1 Intervention
Dose D of AJ1-11095 taken orally by patients.
Group V: Cohort 3Experimental Treatment1 Intervention
Dose C of AJ1-11095 taken orally by patients.
Group VI: Cohort 2Experimental Treatment1 Intervention
Dose B of AJ1-11095 taken orally by patients.
Group VII: Cohort 1Experimental Treatment1 Intervention
Dose A of AJ1-11095 taken orally by patients.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
David H. Koch Center for Cancer Care at Memorial Sloan KetteringNew York, NY
Stanford Cancer InstitutePalo Alto, CA
University of CincinnatiCincinnati, OH
Moffitt Cancer Cancer CenterTampa, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Ajax Therapeutics, Inc.Lead Sponsor
References
Novel Therapies for Myelofibrosis. [2023]The purpose of the review was to provide a contemporary update of novel agents and targets under investigation in myelofibrosis in the Janus kinase (JAK) inhibitor era.
JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis. [2022]Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by uncontrolled blood counts, constitutional symptoms, extramedullary hematopoiesis, and an increased risk of developing acute myeloid leukemia. Janus kinase (JAK) inhibitors are the most common treatment for MF due to their ability to reduce spleen size and improve disease-related symptoms; however, JAK inhibitors are not suitable for every patient and their impact on MF is limited in several respects. Novel JAK inhibitors and JAK inhibitor combinations are emerging that aim to enhance the treatment landscape, providing deeper responses to a broader population of patients with the continued hope of providing disease modification and improving long-term outcomes. In this review, we highlight several specific areas of unmet need within MF. Subsequently, we review agents that target those areas of unmet need, focusing specifically on the JAK inhibitors, momelotinib, pacritinib, itacitinib, and NS-018 as well as JAK inhibitor combination approaches using CPI-0610, navitoclax, parsaclisib, and luspatercept.
Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naïve patients with myelofibrosis: Results of a phase II trial. [2023]Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.
Janus activated kinase inhibition in myelofibrosis. [2021]Janus Activated Kinase (JAK) 2 plays an important role in the pathogenesis of myelofibrosis (MF). Ruxolitinib (INCB018424, Jakafi) is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.
U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. [2022]On November 16, 2011, the U.S. Food and Drug Administration (FDA) granted full approval to ruxolitinib, (Jakafi; Incyte Corp.), an inhibitor of the Janus kinases 1 and 2, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. This approval was based on the results of 2 large randomized phase III trials that enrolled patients with intermediate-2 or high-risk myelofibrosis and compared ruxolitinib with placebo (study 1) or best available therapy (study 2). The primary efficacy endpoint was the proportion of patients who experienced a reduction in spleen volume of ≥ 35% at 24 weeks (study 1) or 48 weeks (study 2). The key secondary endpoint in study 1 was the proportion of patients who experienced a ≥ 50% improvement from baseline in myelofibrosis total symptom score at 24 weeks. The results of these studies showed that a greater proportion of patients treated with ruxolitinib experienced a ≥ 35% reduction in spleen volume as compared with those treated with placebo (42% vs. 1%, P
PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A. [2021]BAY 94-9027 (damoctocog alfa pegol; an extended half-life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged
Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A. [2023]BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUClast, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUClast was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440-3550] IU h/dL versus 2360 [31.8, 2010-2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. ClinicalTrials.gov : NCT03364998.
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. [2021]Rurioctocog alfa pegol (BAX 855) is a novel third-generation recombinant factor VIII whose active ingredient is chemically modified with polyethylene glycol. A global multicenter phase 2/3 study of the product in 137 patients (including 11 patients from Japan) with severe hemophilia A aged 12-65 years, reported an extended half-life and a good tolerability profile, as well as a significantly lower annualized bleeding rate in the prophylactic treatment arm than in the on-demand treatment arm. Using descriptive statistics, a post hoc analysis was performed to compare the pharmacokinetics, safety, and efficacy profiles of the product in the Japanese subpopulation and the overall population. Extended half-life was demonstrated in the Japanese subpopulation. The mean [standard deviation (SD)] annualized bleeding rates in the prophylactic treatment arm were 3.7 (4.7) for the overall population (n = 120) and 4.0 (3.4) for the Japanese subpopulation (n = 11). The proportion of bleeds reported as excellent or good was 94.9% (149/157) in the overall population, whereas that in the Japanese subpopulation was 92.3% (12/13). No FVIII inhibition or anaphylactic reaction was reported in the Japanese subpopulation. The post hoc comparisons demonstrated similar pharmacokinetic, safety, and efficacy profiles between the overall population and the Japanese subpopulation.
PROTECT VIII Kids: BAY 94-9027 (PEGylated Recombinant Factor VIII) safety and efficacy in previously treated children with severe haemophilia A. [2020]BAY 94-9027, a site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII) with extended half-life, demonstrated efficacy for bleed prevention and treatment in previously treated adolescents and adults with severe haemophilia A.
Minimum effective dose of intermediate factor-VIII concentrate in haemophiliacs on home therapy. [2019]The minimum effective dose of intermediate factor-VIII concentrate required for the successful home treatment of spontaneous joint bleeds in six haemophiliacs has been investigated in a randomised trial. 207 episodes of bleeding were included. 5 . 7 units/kg controlled 85% of bleeds, but with a dose of 3 .0 units/kg the risk of failure doubled. This lower dose is inadequate for treatment of bleeds other than those regarded subjectively by the patient as mild. The implications of these findings in terms of availability and usage of factor VIII in this centre are discussed.