A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)

April 17, 2024 updated by: Ajax Therapeutics, Inc.

A Multicenter, Open-Label, Phase 1 Study of AJ1-11095 Administered as Oral Monotherapy in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)

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) and pharmacodynamics (PD) 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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 1, non-randomized, open-label study utilizing a 3+3 sequential dose escalation design followed by an expansion phase. The primary objective will be to evaluate the safety and tolerability of AJ1-11095, and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 2 dose (RP2D). The RP2D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP2D will be based on AE pattern, PK and PD information, in addition to all available safety and efficacy data. Expansion cohorts will be enrolled to gather additional safety and efficacy information and to further refine input for future RP2D discussions. Eligible participants will have PMF, PPV-MF or PET-MF and will have either have relapsed after a response, or be refractory to, at least one prior type I JAK2 inhibitor therapy, either administered as monotherapy or in combination with another drug.

Study Type

Interventional

Enrollment (Estimated)

76

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02115
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
        • Contact:
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Comprehensive Cancer Center
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 18 years of age or older.
  2. Diagnosis of PMF, post-PV MF, or post-ET MF.
  3. DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation status.
  4. Estimated spleen volume ≥450cm3.
  5. MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
  6. ECOG PS of 0, 1, 2, or 3.
  7. Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
  8. ANC ≥1.0×10^9/L.
  9. Platelet count ≥75×10^9/L.
  10. eGFR ≥40 mL/min.
  11. Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
  12. AST and ALT ≤3.0 × ULN.
  13. QTcF ≤480 msec.

Exclusion Criteria:

  1. Prior splenectomy.
  2. Splenic irradiation within 3 months prior to first dose of study drug.
  3. Ongoing use of systemic corticosteroids at dose equivalent to >10mg/day of prednisone.
  4. Uncontrolled intercurrent illness such as an acute infection.
  5. Chronic active or acute hepatitis B or C infection.
  6. Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is permitted until 5 days before starting protocol therapy).
  7. Use of a JAK2 inhibitor in the previous 10 days.
  8. Use of erythropoiesis stimulating agents (unless stable for >8 weeks).
  9. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
  10. Unable or unwilling to undergo CT or MRI for spleen size imaging.
  11. Pregnant or breastfeeding.
  12. Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a concomitant medication.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Dose A of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Cohort 2
Dose B of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Cohort 3
Dose C of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Cohort 4
Dose D of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Cohort 5
Dose E of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Dose Expansion Cohort 1
Candidate RP2D of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor
Experimental: Dose Expansion Cohort 2
Alternative candidate RP2D of AJ1-11095 taken orally by patients.
Drug: AJ1-11095
Type II JAK2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with Dose Limiting Toxicities (DLTs)
Time Frame: Baseline through study completion, an average of 1 year
Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals.
Baseline through study completion, an average of 1 year
To establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AJ1-11095
Time Frame: Baseline through study completion, an average of 1 year
Safety evaluations will occur consistently for each patient and across patients to assess MTD or RP2D. See description of safety evaluations described in outcomes 1 and 2 mentioned above.
Baseline through study completion, an average of 1 year
Number of patients with treatment-emergent adverse events as assessed by CTCAE v 5.0.
Time Frame: Baseline through study completion, an average of 1 year
Treatment Emergent AEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability of AJ1-11095.
Baseline through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess clinical response to AJ1-11095 evaluated by the Total Symptom Score (TSS).
Time Frame: Baseline through Week 24
Number and proportion of patients with an improvement of ≥50% from Baseline in Total TSS as well as time to TSS response and duration of TSS response using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. The TSS is a 7 question assessment form with lower scores indicating better outcomes.
Baseline through Week 24
To assess clinical response to AJ1-11095 evaluated by spleen volume assessments.
Time Frame: Baseline through Week 24
Spleen volume reduction (SVR) of ≥35% from Baseline measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Baseline through Week 24
To assess clinical response to AJ1-11095 evaluated by spleen length assessments.
Time Frame: Baseline through Week 24
Proportion of subjects with ≥50% reduction in length of spleen assessed by palpation.
Baseline through Week 24
To assess clinical response to AJ1-11095 evaluated through spleen size improvement.
Time Frame: Baseline through Week 24
Time to spleen size improvement response measured by patient and across all patients.
Baseline through Week 24
To evaluate the Area Under the Curve (AUC) of AJ1-11095
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated.
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Cmax of AJ1-11095
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
The maximum observed plasma concentration will be evaluated.
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Tmax of AJ1-11095
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
The duration of time taken to reach Cmax will be evaluated.
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the half-life of AJ1-11095
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).
The depletion of AJ1-00195 in the body will be observed over time.
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), Day 8, 15, 22, and Cycle 2 (Day 1 and 24 hrs post).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ajax Therapeutics, Inc.

Investigators

  • Principal Investigator: John Mascarenhas, M.D., Mt. Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 15, 2024

Primary Completion (Estimated)

August 15, 2026

Study Completion (Estimated)

February 15, 2027

Study Registration Dates

First Submitted

March 13, 2024

First Submitted That Met QC Criteria

March 26, 2024

First Posted (Actual)

April 3, 2024

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AJX-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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