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

This is a Phase 2 open-label, single-arm design with dose escalation by subject cohort and with the potential for individual titration (dose increase or decrease) within each cohort. Five PTG-300 dose levels/regimens are planned to be tested for each subpopulation of beta-thalassemia (NTD and TD) on separate arms: Cohort 1: 3mg subcutaneous (SC) weekly (n = 6 subjects per subpopulation) Cohort 2: 10mg SC weekly (n = 6 subjects per subpopulation) Cohort 3: 20mg SC weekly (n = 6 subjects per subpopulation) Cohort 4a: 40mg SC weekly (n = 6 subjects per subpopulation) Cohort 4b: 40mg SC every 2 weeks (n = 6 subjects per subpopulation) Two additional cohorts (Cohorts 5 and 6, n=6/cohort per subpopulation) will include subjects between 12- less than 18 years of age at a starting dose of 3mg and 10mg/weekly respectively, with the potential for individual titration (dose increase or decrease) based on the titration algorithm. A cohort may be enrolled at the maximum dose of 80mg if there is insufficient effect at 40mg. Additionally, up to approximately 12 subjects in each subpopulation may be enrolled if further data are required to identify a safe starting dose, dose frequency, dose escalation scheme or dose range. Furthermore, a lower dose than 40mg (e.g.20mg) may be tested with dosing every 2 weeks if data support it. On the contrary, a cohort may not be initiated if based on the analysis of the data from prior cohorts, additional benefit is not expected or a potential increased risk is anticipated. The duration of dosing is 12 weeks for the NTD and 16 weeks for the TD subjects. The different duration of treatment in each subpopulation is based on the expected time required to assess their specific endpoints. Study visits will occur at screening (Day -28 to -1) and weekly during the first 4 weeks of each dose for safety assessment. After the initial 4 weeks, visits will occur according to the study plan. After completing the Phase 2 study, subjects may elect to participate in a separate open label long term extension protocol. A follow-up visit will be scheduled 30 (±5) days after the last dose, for those subjects not continuing in the extension study.