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)

Primary Myelofibrosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06343805
• Other study ID #: AJX-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 15, 2024
• Est. completion date: February 15, 2027

Study information

• Verified date: May 2024
• Source: Ajax Therapeutics, Inc.
• Contact: David Steensma, M.D.
• Phone: 917-410-7250
• Email: david[@]ajaxtherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 76
• Est. completion date: February 15, 2027
• Est. primary completion date: August 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• PMF
• Polycythemia
• Polycythemia Vera
• Post-Essential Thrombocythemia Myelofibrosis
• Post-Polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• AJ1-11095
Type II JAK2 Inhibitor

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ajax Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with treatment-emergent adverse events as assessed by CTCAE v 5.0.	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
Primary	Number of patients with Dose Limiting Toxicities (DLTs)	Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals.	Baseline through study completion, an average of 1 year
Primary	To establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AJ1-11095	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
Secondary	To assess clinical response to AJ1-11095 evaluated by the Total Symptom Score (TSS).	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
Secondary	To assess clinical response to AJ1-11095 evaluated by spleen volume assessments.	Spleen volume reduction (SVR) of =35% from Baseline measured by magnetic resonance imaging (MRI) or computed tomography (CT).	Baseline through Week 24
Secondary	To assess clinical response to AJ1-11095 evaluated by spleen length assessments.	Proportion of subjects with =50% reduction in length of spleen assessed by palpation.	Baseline through Week 24
Secondary	To assess clinical response to AJ1-11095 evaluated through spleen size improvement.	Time to spleen size improvement response measured by patient and across all patients.	Baseline through Week 24
Secondary	To evaluate the Area Under the Curve (AUC) of AJ1-11095	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).
Secondary	To evaluate the Cmax of AJ1-11095	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).
Secondary	To evaluate the Tmax of AJ1-11095	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).
Secondary	To evaluate the half-life of AJ1-11095	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).