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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)

Sponsor: Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company

NCT ID: NCT06343805

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
LY5830966 (drug)
How long the study runs
Study runs about 50 months (dates as stated)
About the drug or intervention
LY5830966 — drug: Type II JAK2 Inhibitor
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
256
Started
2024-10-03
Last checked
2026-10

Plain English Summary

What is this study?

  • • Testing a new treatment for primary myelofibrosis
  • • Phase1 - 256 participants
  • • 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

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with primary myelofibrosis

Where?

  • • London - Guy's Hospital
  • • Oxford - Genesis Cancer Care UK Limited - Oxford

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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.

More detail

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.

Primary Myelofibrosis

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What we know so far

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Biomarkers mentioned

eGFR

Treatment history

Treatments you must have had:

  • ✓ at least 1 type I JAK2 inhibit
  • ✓ including but not limited to interferon-based therapies

What the study is looking for

  • ✓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...
  • ✓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...
  • ✓activity scale performance score (ECOG PS) of 0, 1, 2, or 3.

Who cannot take part

  • ✗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...
  • ✗Active, uncontrolled systemic infection or active Hepatitis B or C
  • ✗drug treatment 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).
See the full criteria
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%.

Where Is This Study? (2 UK sites)

Guy's Hospital

London, United Kingdom

NOT_YET_RECRUITING
Site contact (verified)
Claire Harrison, MD07939059512

Genesis Cancer Care UK Limited - Oxford

Oxford, United Kingdom

NOT_YET_RECRUITING
Hospital R&D contact (matched)

Research Support Team

research@oxfordhealth.nhs.uk01865 902401

How to Get in Touch

David Steensma, M.D.

Sponsor contact

CONTACT

917-410-7250 david@ajaxtherapeutics.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-10