A Phase 1 Study of LY5830966 in Participants 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)

September 14, 2026 updated by: Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

A Phase 1, Open-Label Study of LY5830966, a Type II JAK2 Inhibitor, in Patients With Myelofibrosis Previously Treated With a Type I JAK2 Inhibitor, JAK2 Inhibitor-Naïve Myelofibrosis, or High-risk Relapsed/Refractory Polycythemia Vera

J8G-MC-JDIA (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 Janus Kinase 2 (JAK2) inhibitor, LY5830966, in participants with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 LY5830966 and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 3 dose (RP3D). The RP3D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP3D will be based on adverse event (AE) pattern, pharmacokinetics (PK) and biomarker 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 RP3D 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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
256

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Paris, France
        • Recruiting
        • AP-HP Hopital Saint-Louis
        • Contact:
          • Jean-Jacques Kiladjian
  • Italy
    • Italy
      • Bologna, Italy, Italy
        • Not yet recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
        • Contact:
          • Francesca Palandri, MD
      • Milan, Italy, Italy
        • Not yet recruiting
        • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
        • Contact:
          • Francesco Passamonti, MD
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Clinic Barcelona
        • Contact:
          • Ana Moreno Triguero
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Ramon y Cajal
        • Contact:
          • Valentin Garcia-Gutierrez
    • Spain
      • Madrid, Spain, Spain
        • Recruiting
        • Hospital General Universitario Gregorio Marañón
        • Contact:
          • Santiago Osorio-Prendes, MD
          • Phone Number: 0034915868443
  • United Kingdom
    • UK
      • London, UK, United Kingdom
        • Not yet recruiting
        • Guy's Hospital
        • Contact:
          • Claire Harrison, MD
          • Phone Number: 07939059512
      • Oxford, UK, United Kingdom
        • Not yet recruiting
        • Genesis Cancer Care UK Limited - Oxford
        • Contact:
          • Adam Mead, MD
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford Cancer Institute
        • Contact:
          • William Shomali, MD
          • Phone Number: 650-498-6000
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Cancer Center
        • Contact:
          • Andrew Kuykendall, MD
          • Phone Number: 813-745-4639
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Contact:
          • Abdulraheem Yacoub, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Gabriela Hobbs, MD
          • Phone Number: 617-724-1124
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Dana Farber Cancer Institute
        • Contact:
          • Jacqueline Garcia, MD
          • Phone Number: 617-632-1906
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
          • Kristen Pettit, MD
          • Phone Number: 734-647-2829
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
          • Stephen Oh, MD
          • Phone Number: 314-362-8814
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
          • John Mascarenhas, MD
          • Phone Number: 212-241-8839
      • New York, New York, United States, 10021
        • Recruiting
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering
        • Contact:
          • Raajit Rampal, MD
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Levine Cancer Institute
        • Contact:
          • Michael Grunwald, MD
          • Phone Number: 980-442-4363
    • Ohio
      • Cincinnati, Ohio, United States, 45221
        • Recruiting
        • University of Cincinnati
        • Contact:
          • Eric Vick, MD
          • Phone Number: 513-213-3203
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Comprehensive Cancer Center
        • Contact:
          • Uma Borate, MD
          • Phone Number: 614-685-9828
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
          • Prithviraj Bose, MD
          • Phone Number: 713-792-7747

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of PMF, post-PV MF, or post-ET MF.
  • Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1, Intermediate-2 or High-risk MF with less than or equal to (≤)10% blasts, regardless of JAK2 mutation status.
  • Estimated spleen volume greater than or equal to (≥)450 cubic centimeter (cm ³)
  • Myelofibrosis Symptom Assessment Form, version 4.0 (MFSAF v.4.0) TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
  • Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1, 2, or 3.
  • Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
  • Absolute neutrophil count greater than or equal to 1,000 per microliter of blood (ANC ≥1.0×10^9/L).
  • Platelet count ≥75×10^9/L.
  • Estimated glomerular filtration rate greater than or equal to 45 milliliters per minute per 1.73 square meters (eGFR ≥45 mL/min/1.73m²).
  • Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit normal (ULN).
  • QTcF ≤470 msec.

Polycythemia vera (PV) Only

  • Confirmed diagnosis of PV
  • Participants must have high-risk disease as defined by 60 years of age or older and/or have prior history of thrombotic event
  • R/R or intolerant to at least one line of prior therapy including but not limited to interferon-based therapies, ruxolitinib, or hydroxyurea (HU) as defined by European LeukemiaNet (ELN) criteria

Exclusion Criteria:

  • Prior splenectomy or splenic irradiation within 3 months.
  • Ongoing use of systemic corticosteroids at dose equivalent to greater than (>) 20 milligrams per day (mg/day) of prednisone.
  • Active, uncontrolled systemic infection or active Hepatitis B or C
  • Chemotherapy in the previous 4 weeks or prior JAK2 inhibitor not discontinued per required washout prior to first dose
  • Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
  • Pregnant or breastfeeding: males planning to father a child during treatment and for 3 months after last dose.
  • Requirement for therapy with a medication that is a strong Cytochrome P450 3A4 CYP3A4 inhibitor as a concomitant medication.
  • Currently on an interventional therapeutic trial in the treatment phase.
  • Significant cardiovascular disease
  • Active second primary malignancy (or diagnosed within 2 years) at high risk of progression, with standard exceptions (treated skin cancer, in situ cervical cancer, curatively treated localized breast/prostate cancer)
  • Prolongation of the corrected QTcF ≥470 millisecond during screening
  • Individual with a history of (noninfectious) pneumonitis/interstitial lung disease.

First line (1L) MF only:

  • Prior treatment with JAK2 inhibitors

High-risk R/R PV only:

  • Prior PV-directed therapy without required washout
  • Active or chronic bleeding within 2 months prior to enrollment
  • Clinically significant thrombosis (e.g., pulmonary embolism, deep vein thrombosis, or splenic vein thrombosis) within 2 months prior to enrollment
  • Requires phlebotomy at hematocrit levels <45%.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Dose A of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Cohort 2
Dose B of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Cohort 3
Dose C of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Cohort 4
Dose D of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Cohort 5
Dose E of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Dose Expansion Cohort 1
Candidate RP3D of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Dose Expansion Cohort 2
Alternative candidate RP3D of LY5830966 taken orally by participants.
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Dose Exploration Cohort 1
Dose F of LY5830966 taken orally by participants
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Dose Exploration Cohort 2
Dose G of LY5830966 taken orally by participants
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095
Experimental: Dose Exploration Cohort 3
Dose H of LY5830966 taken orally by participants[
Drug: LY5830966
Type II JAK2 Inhibitor
Other Names:
  • AJ1-11095

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Number of patients with treatment-emergent adverse events (TEAEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI 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 LY5830966.
Baseline through study completion, an average of 1 year
To establish the maximum tolerated dose (MTD) and/or recommended phase 3 dose (RP3D) of LY5830966
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 RP3D. See description of safety evaluations described in outcomes 1 and 2 mentioned above.
Baseline through study completion, an average of 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To assess clinical response to LY5830966 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 LY5830966 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 LY5830966 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 LY5830966 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 LY5830966
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), 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), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Cmax of LY5830966
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), 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), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the Tmax of LY5830966
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), 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), and Cycle 2 (Day 1 and 24 hrs post).
To evaluate the half-life of LY5830966
Time Frame: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), 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), 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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 23, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 3, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 27978
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • AJX-101 (Other Identifier: Ajax Therapeutics, Inc.)
  • 2025-522033-64-00 (Ctis)
  • J8G-MC-JDIA (Other Identifier: Eli Lilly and Company)

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

product manufactured in and exported from the U.S.

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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