A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 in Participants With Myelofibrosis

An Open-label, Phase IIa Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral GB2064 (a LOXL2 Inhibitor) in Participants With Myelofibrosis (MF)

This study is an open label, phase IIa trial in subjects with Myelofibrosis

Study Overview

• Status: Active, not recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: GB2064

Detailed Description

This study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of orally administered GB2064 a LOXL-2 inhibitor over 9 months. Subjects will receive doses of GB2064, given twice per day to participants with primary or secondary Myelofibrosis

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Canberra, Australia, 2605
    • Woden Dermatology
• Germany
  • Düsseldorf, Germany, 40225
    • Heinrich-Heine-University Dusseldorf
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Leipzig, Germany, 04103
    • Universität Leipzig
  • München, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universitaet Munchen
• Italy
  • Bologna, Italy, 40138
    • University of Bologna Sant Orsola Malpighi
  • Firenze, Italy, 50134
    • Azienda Ospedaliero-Universitaria Careggi
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero-Universitaria San Luigi Gonzaga di Orbassano
  • Varese, Italy, 21100
    • Azienda Socio-Sanitaria Territoriale dei Sette Laghi
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Andersson Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must satisfy all of the following criteria at the Screening visit:

1. Adult male or female participants ≥ 18 years of age at enrolment:

   1. Female participants may be of non-childbearing potential defined as permanently sterile or postmenopausal, or female participants considered to be of childbearing potential who agree to use highly effective birth control methods until 90 days after the follow-up visit. Female participants should refrain from ova donation from the date of Enrolment (Day -1) until 90 days after the follow-up visit.
   2. Male participants will agree to use contraception throughout the study and until 90-days after the Follow-up visit. Male participants must agree to refrain from sperm donation from the date of Enrolment (Day -1) until 90 days after the follow-up visit.
2. Diagnosis of PMF or SMF with intermediate -2 or high-risk disease according to the Dynamic International Prognostic Scoring System (DIPSS)-plus or if with low risk disease then with symptomatic splenomegaly as defined by sonographic assessment as spleen length of >12 cm or by physical examination as ≥ 5 cm below left costal margin.
3. Participants who are not currently taking a Janus kinase (JAK) inhibitor (e.g. ruxolitinib or fedratinib) and are therefore refractory, intolerant or ineligible for a JAK inhibitor according to appropriate guidelines (including local guidelines).
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

5. Required baseline laboratory status:

   1. Absolute platelet count (APC) ≥ 50 x 109/L
   2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mm3)
   3. Serum direct bilirubin ≤ 2.0 x ULN (upper limit of normal)
   4. AST (SGOT) or ALT (SGPT) [if both measured, then this applies to both measurements] ≤ 2.5 x ULN, except for participants with MF involvement of the liver who must have levels ≤ 5 x ULN
   5. Estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) (CrCl calculated by the Cockroft and Gault method) ≥ 30 ml/min/1.73 m2.
   6. Peripheral blood blasts <10%
6. Treatment-related toxicities from prior therapies must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1.
7. Participants must have a documented history of transfusion records (if there have been any such transfusions) in the preceding 12 weeks to Day 1.

Exclusion Criteria:

1. Current treatment with a JAK inhibitor (e.g. ruxolitinib or fedratinib) or a history of treatment with a JAK inhibitor within two weeks of enrolment.
2. Positive hepatitis panel and/or positive HIV test.
3. Any concurrent severe and/or uncontrolled medical conditions that could increase the participant's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities. Any planned major surgery during the study period

4. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

   1. History or presence of ventricular tachyarrhythmia.
   2. Presence of unstable atrial fibrillation (ventricular response > 100 bpm); Participants with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
   3. Clinically significant resting bradycardia (< 50 bpm) and use of a cardiac pacemaker or implantable cardioverter defibrillator.
   4. Angina pectoris or acute myocardial infarction ≤ 90 days prior to starting study drug.
   5. Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen).
5. Participants who are currently receiving chronic (> 14 days) treatment with corticosteroids at a dose > 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug.
6. Participants with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GB2064 as per physician's opinion.
7. Participants who received radiotherapy within the last month prior to screening procedures, or patients who received splenectomy in the previous three months or are scheduled for the procedure in the next three months.
8. Participants who had a history of malignancy in the past 3 years, except for treated early stage squamous, basal cell carcinoma or treated, localised prostate cancer.
9. Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy.
10. Previous history of Progressive Multifocal Leuko-encephalopathy (PML).
11. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive β- HCG laboratory test.
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment. Highly effective contraception methods must be used.
13. Sexually active males must use a condom during intercourse while taking the drug and for 90 days after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
14. Hypersensitivity to GB2064 and/or its excipients.
15. Participants unable or unwilling to comply with protocol requirements.
16. Participants related to PI/site staff.
17. Participants who have had a hematopoietic stem cell transplantation.
18. Participants who are eligible, have a donor and are willing to undergo a hematopoietic stem cell transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GB2064; GB2064 will be administered orally as 4 x 250 mg tablets twice a day.	Drug: GB2064; GB2064 (formerly PAT-1251) is a high-affinity, selective, mechanism-based, small molecule inhibitor of LOXL2, administered twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of GB2064: AE	Incidence and severity of adverse events as reported by investigators	9 Months

Collaborators and Investigators

• Sponsor: Galecto Biotech AB
• Collaborators: OPIS s.r.l
• Investigators: Principal Investigator: Richard F Schlenk, MD, Universitätsklinikum Heidelberg, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Myelofibrosis; GB2064; LOXL-2; PAT1251
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: MYLOX-1; 2020-003087-45 (EudraCT Number)

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