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)
Recruiting
Phase 1Interventional Study
Primary MyelofibrosisPost-Essential Thrombocythemia MyelofibrosisPost-Polycythemia Vera MyelofibrosisPMFPPV-MFPET-MF
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
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At a Glance
Age
18 and older
Sex
Any
Trial phase
Phase 1
Study type
Interventional
Purpose
Treatment
Participants needed
76 (estimated)
Sponsor
Ajax Therapeutics, Inc. · Industry
Who this trial is looking for
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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.
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Eligibility Criteria
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 …
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 ≥45 mL/min/1.73m2.
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 Type I JAK2 inhibitor must have been discontinued for at least 5 days or 5 half-lives prior to dosing (whichever is longer).
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.
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