ß-Thalassemia Subjects with Chronic Anemia (transfusion and non transfusion dependent) MedDRA version: 20.0 Level: PT Classification code 10043391 Term: Thalassaemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: PTG-300
Product Code: PN-8518A
Pharmaceutical Form: Injection
Current Sponsor code: PTG-300
Other descriptive name: 1-(3-METHYLBUTANOYL)-L-ASPARTYL-L-THREONYL-L-HISTIDYL-L-PHENYLALANYL-L
Sponsors
Protagonist Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 5–15 days prior to dosing. Are the trial subjects under 18? yes Number of subjects for this age range: 60 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects with Sickle Cell disease, Hgb H, Hb Bart’s hydrops foetalis or hemoglobin S 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 < 1000/µL b. Platelet count < 100,000/µL c. Estimated glomerular filtration rate (eGFR) < 60 d. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN) 7. Treatment with hydroxyurea = 24 weeks prior to screening (unless approved by the Medical Monitor). 8. Use of erythropoiesis-stimulating agent (ESA) = 24 weeks prior to screening. 9. Chronic use of systemic glucocorticoids (anti-inflammatory dose for more than 14 days) = 12 weeks prior to screening (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. 16. Having undergone splenectomy = 24 weeks prior to screening. 17. NTD subjects receiving iron chelation therapy (unless approved by the Medical Monitor). 18. TD subjects who started regular transfusions before age 2 years. 19. TD subjects who required more than 140 mL pure RBC/kg in the year prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of PTG-300 in subjects with NTD and TD ß-thalassemia. 2. To obtain preliminary evidence of PTG-300’s efficacy for treating chronic anemia in subjects with ß-thalassemia. 3. To identify the optimal starting dose, titration algorithm, dose range and dose regimen to be used in Phase 3 studies.;Secondary Objective: 1. To evaluate the pharmacokinetics (PK) of PTG-300. 2. To evaluate the pharmacodynamic (PD) effects of PTG-300. 3. To evaluate the immunogenicity of PTG-300.;Primary end point(s): NTD: • Proportion of responders, where responders are defined as: - Subjects who achieve an increase in Hgb = 1.0 g/dL without transfusion, confirmed by a successive measurement at least 1 week later • Hgb change from baseline TD: • Proportion of responders, where responders are defined as: - Subjects who achieve = 20% reduction in the RBC units required over an 8-week period • Change from baseline in the number of units of RBC required;Timepoint(s) of evaluation of this end point: NTD: Every Visit. TD: over an 8-week period under the same dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NTD: • Hgb level • Proportion of subjects who achieve an increase in Hgb = 1.5 g/dL without transfusion, confirmed by a successive measurement at least 1 week later • Duration of Hgb change of =1.0 g/dL from baseline without transfusion • Duration of Hgb change of =1.5 g/dL from baseline without transfusion • Change from baseline in the following PD parameters: serum iron, ferritin, transferrin saturation (TSAT) TD: • Proportion of subjects who achieve = 33% reduction in the RBC units required over an 8-week period • Duration of response (defined as = 20% reduction in the RBC units required over an 8-week period) • Percent change from baseline in the RBC units required • Best percent change from baseline in the RBC units required over an 8-week period • Number of RBC units required • Change from baseline to in the following PD parameters: serum iron, ferritin, transferrin, TSAT;Timepoint(s) of evaluation of this end point: NTD: Every Visit. TD: over an 8-week period under the same dose. | — |
Countries
Greece, Italy, Lebanon, Malaysia, Thailand, Tunisia, Turkey, United Kingdom, United States
Contacts
Public ContactClinical-Regulatory Info Group
Protagonist Therapeutics, Inc.
Outcome results
None listed