Myelofibrosis
Conditions
Keywords
GB2064, Myelofibrosis, LOXL-2, PAT1251
Brief summary
This study is an open label, phase IIa trial in subjects with Myelofibrosis
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
Interventions
DRUGGB2064
GB2064 (formerly PAT-1251) is a high-affinity, selective, mechanism-based, small molecule inhibitor of LOXL2, administered twice a day
Sponsors
OPIS s.r.l
Galecto Biotech AB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All subjects eligible for the study will receive GB2064 1000mg, twice a day
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of GB2064: AE | 9 Months | Incidence and severity of adverse events as reported by investigators |
Countries
Australia, Germany, Italy, United States
Outcome results
None listed