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

NCT04679870 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MYLOX-12020-003087-45
• Study Type: interventional
• Target: 21
• Locations: 4 countries
• Sites: 11

Brief Summary

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

Conditions

Myelofibrosis

Keywords

GB2064; Myelofibrosis; LOXL-2; PAT1251

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of GB2064: AE

  Incidence and severity of adverse events as reported by investigators

  9 Months

Study Arms (1)

GB2064

EXPERIMENTAL

GB2064 will be administered orally as 4 x 250 mg tablets twice a day.

Drug: GB2064

Interventions

GB2064 DRUG

GB2064 (formerly PAT-1251) is a high-affinity, selective, mechanism-based, small molecule inhibitor of LOXL2, administered twice a day

GB2064

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy all of the following criteria at the Screening visit:
• Adult male or female participants ≥ 18 years of age at enrolment:
• 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.
• 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.
• 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.
• 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).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Required baseline laboratory status:
• Absolute platelet count (APC) ≥ 50 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/mm3)
• Serum direct bilirubin ≤ 2.0 x ULN (upper limit of normal)
• 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
• Estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) (CrCl calculated by the Cockroft and Gault method) ≥ 30 ml/min/1.73 m2.
• Peripheral blood blasts \<10%
• Treatment-related toxicities from prior therapies must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1.

You may not qualify if:

• 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.
• Positive hepatitis panel and/or positive HIV test.
• 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
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of ventricular tachyarrhythmia.
• Clinically significant resting bradycardia (\< 50 bpm) and use of a cardiac pacemaker or implantable cardioverter defibrillator.
• Angina pectoris or acute myocardial infarction ≤ 90 days prior to starting study drug.
• 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).
• 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.
• Participants with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GB2064 as per physician's opinion.
• 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.
• 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.
• Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy.
• Previous history of Progressive Multifocal Leuko-encephalopathy (PML).
• 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.

Sponsors & Collaborators

• Galecto Biotech AB: lead
• OPIS s.r.l: collaborator

Study Sites (11)

MD Andersson Cancer Hospital

Houston, Texas, 77030, United States

Location

Woden Dermatology

Canberra, 2605, Australia

Location

Heinrich-Heine-University Dusseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universität Leipzig

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar der Technischen Universitaet Munchen

München, 81675, Germany

Location

University of Bologna Sant Orsola Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga di Orbassano

Orbassano, 10043, Italy

Location

Azienda Socio-Sanitaria Territoriale dei Sette Laghi

Varese, 21100, Italy

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Richard F Schlenk, MD

  Universitätsklinikum Heidelberg, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All subjects eligible for the study will receive GB2064 1000mg, twice a day

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 22, 2020
• Study Start: June 9, 2021
• Primary Completion: December 31, 2023
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); AU (1); IT (5); DE (4)