Chronic anemia due to ineffective erythropoiesis (IE) in subjects with ß thalassemia Thalassemia
Conditions
Interventions
Five PTG-300 dose levels/regimens are planned to be tested for each subpopulation of ß thalassemia (NTD and TD) on separate arms:
• Cohort 1: 3mg subcutaneous (SC) weekly (n = 6 subjects per subpopula
3mg subcutaneous (SC) weekly (n = 6 subjects per subpopulation)
10mg SC weekly (n = 6 subjects per subpopulation)
20mg SC weekly (n = 6 subjects per subpopulation)
40mg SC weekly (n = 6 subjects per subpopulation)
40mg SC every 2 weeks (n = 6 subjects per subpopulation)
Cohort 4a
Cohort 4b
Sponsors
Protagonist Therapeutics Inc
Eligibility
Sex/Gender
All
Age
12 Years to 65 Years
Inclusion criteria
Inclusion criteria: All subjects must meet ALL of the following inclusion criteria to be enrolled: 1. Male and female subjects aged 18 to 65 years, inclusive (Cohorts 1 4b). 2. Male and female subjects aged 12- 45 days. 2. Last RBC transfusion 5–10 days prior to dosing.
Exclusion criteria
Exclusion criteria: Subjects must meet NONE of the following exclusion criteria to be enrolled: 1. Subjects with the diagnosis of ß-thalassemia major (genotype homozygous ß0/ß0 or compound heterozygous ß0/ß+ with a major phenotype). 2. Infection requiring hospitalization or IV antimicrobial therapy, or opportunistic infection within 6 months of dosing, any infection requiring antimicrobial therapy within 2 weeks of dosing; history of infection with human immunodeficiency virus (HIV). 3. Subject has a concurrent clinically significant, unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic or other medical disorder that, in the opinion of the Investigator, might confound the results of the study or pose additional risk to the subject by their participation in the study. 4. Known primary or secondary immunodeficiency. 5. History within 6 months of screening of any of the following: myocardial infarction, unstable angina, transient ischemic attack, decompensated heart failure requiring hospitalization, congestive heart failure (New York Heart Association Class 3 or 4), uncontrolled arrhythmias, cardiac revascularization, stroke, uncontrolled hypertension (resting systolic blood pressure [BP] > 160mmHg or resting diastolic BP > 100mmHg on more than one occasion) or uncontrolled diabetes (Hgb A1c > 9% or > one episode of severe hypoglycemia). 6. Clinically meaningful laboratory abnormalities at screening including, but not limited to, the ranges below: a. Absolute neutrophil count 1.5 x ULN 7. Treatment with hydroxyurea = 24 weeks prior to randomization. 8. Use of erythropoiesis-stimulating agent (ESA) = 24 weeks prior to randomization. 9. Chronic use of systemic glucocorticoids (anti-inflammatory dose for more than 14 days) = 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed). 10. Pregnant or lactating females. 11. Any surgical procedure requiring general anesthesia within 1 month prior to screening or planned elective surgery during the study. 12. History of malignant neoplasms within 5 years prior to screening. Subjects who are cancer-free for the 5 years before screening may be enrolled. Subjects with carcinoma in situ, adequately treated non-metastatic basal cell skin cancer, or squamous cell skin cancer that has not recurred for at least 1 year prior to screening, may be enrolled. 13. Current or recent history of alcohol dependence or illicit drug use within 1 year prior to screening. 14. Subject is mentally or legally incapacitated at the time of screening visit or has a history of clinically significant psychiatric disorders that would impact the subject’s ability to participate in the trial according to the Investigator. Note: Subjects who have had situational depression or adjustment disorder or treated depression may be enrolled at the discretion of the Investigator. 15. Concurrent participation in any other interventional study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: NTD patients: Mean Hgb change from baseline;Timepoints: 4-week period under the same dose;Measure: Hemoglobin test at each dose ;Name: NTD subjects who achieve an increase in Hgb = 1.0 g/dL without transfusion ;Timepoints: 4-week period under the same dose.;Measure: Hemoglobin test at each dose ;Name: TD Patients: achieve = 20% reduction in the RBC units required over an 8 week period;Timepoints: 8 week period;Measure: RBC units transfused;Name: TD patients: Mean change from baseline in the number of units of RBC required under each dose ;Timepoints: 8 week period;Measure: RBC units transfused | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: NTD patients: Mean Hgb ;Timepoints: at the end of treatment;Measure: Hgb test;Name: Proportion of subjects who achieve an increase in Hgb = 1.5 g/dL ;Timepoints: at any time up to Week 12 in NTD;Measure: Hgb test;Name: Duration of response ;Timepoints: NTD: Hgb change of =1 g/dL without transfusion; or = 20% reduction in the RBC units required over an 8 week period in TD patients;Measure: Hbg test in NT; RBC units transfused in TD;Name: Time to response ;Timepoints: Hgb change of =1 g/dL without transfusion in NTD or = 20% reduction in the RBC units required over an 8 week period in TD;Measure: Hbg test in NT; RBC units transfused in TD;Name: TD patients: Mean number of RBC units required ;Timepoints: at each dose over the 16 week period;Measure: RBC units transfused;Name: Change from baseline in liver iron content ;Timepoints: Week 16 for TD or week 12 for NTD;Measure: LIC measured by MRI | — |
Countries
Greece, Italy, Lebanon, Malaysia, Thailand, Tunisia, Turkey, United Kingdom, United States of America
Contacts
Public ContactAziz Zoghbi
Regional Manager
Outcome results
None listed