Study of PTG-300 in Non-Transfusion Dependent and Transfusion-Dependent Beta-Thalassemia Subjects With Chronic Anemia

A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects With Chronic Anemia

This is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort . The study is designed to monitor the PTG-300 safety profile, to obtain preliminary evidence of efficacy of PTG-300 for the treatment in β-thalassemia.

This is a Phase 2 open-label, single-arm design study with dose escalation by subject cohort and with the potential for individual titration (dose increase or decrease) within each cohort. The study is designed to monitor the PTG-300 safety profile, to obtain preliminary evidence of efficacy of PTG-300 for the treatment of chronic anemia in β-thalassemia and to evaluate the appropriate dosing regimen for PTG-300 in the target population

Main Inclusion Criteria:

1. Male and female subjects aged 18 to 65 years, inclusive (Cohorts 1-4b).
2. Male and female subjects aged 12-<18 years, with a minimum weight of 30 kg (Cohorts 5 and 6).
3. Documented diagnosis of β-thalassemia with no other Hgb abnormality.

Inclusion criteria applicable only for NTD β-thalassemia subjects:

1. Mean Hgb < 10.0 g/dL of two measurements (one performed 7-28 days prior to dosing and the other performed within 7 days prior to dosing).
2. Requirement of < 6 units RBC transfusion in a 24 week period with the last transfusion at least 8 weeks before screening.

Inclusion criteria applicable only for TD β-thalassemia subjects:

1. Transfusion requirement of at least 6 units of RBC in the 24 weeks prior to screening with no transfusion free period > 45 days.
2. Last RBC transfusion 5-10 days prior to dosing.

Main 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. Pregnant or lactating females.