E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
β-Thalassemia Subjects with Chronic Anemia (transfusion and non transfusion dependent) |
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E.1.1.1 | Medical condition in easily understood language |
Blood disease that reduces the production of hemoglobin (protein needed to carry oxygen in the red blood cells) causing anemia. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043391 |
E.1.2 | Term | Thalassaemia beta |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1.To assess the long-term safety and tolerability of PTG-300 in subjects with TD and NTD β-thalassemia |
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E.2.2 | Secondary objectives of the trial |
1.To assess the long-term efficacy of PTG-300 for treating chronic anemia in subjects with β-thalassemia
2.To assess pharmacokinetic (PK), pharmacodynamic (PD) and immunogenicity with the long-term administration of PTG-300
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.NTD and TD β-thalassemia subjects who completed Week 12 and Week 16 respectively in Study PTG-300-02.
2.Women of childbearing potential (WOCBP) and men agree to use a highly effective contraceptive measure (base on the Clinical Trial Facilitation Group [CTFG]) during the duration of the study and for 4 weeks after the last dose of study drug in the case of women and 90 days after the last dose of study drug in the case of men.
3.For WOCBP, a negative urine pregnancy test within 24 hours prior to the first dose of study medication in this study.
4.Subjects or legal guardians (in the case of minors) understand the study procedures and agree to participate in the study by giving written informed consent.
5.Subjects, or legal representative (in the case of minors) are willing and able to adhere to the study visit schedule and other protocol requirements.
6.Subjects between 12-<18 years of age understand and provide the assent to participate in the study, according to local guidelines.
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E.4 | Principal exclusion criteria |
1.Subjects who discontinued prematurely from study 300-02 (before Week 12 in NTD and Week 16 in TD)
2.Clinically meaningful laboratory abnormalities at Screening.
3.Pregnant or lactating females.
4.Current history of alcohol dependence or illicit drug use.
5.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.
6.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.
7.Concurrent participation in any other interventional study.
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E.5 End points |
E.5.1 | Primary end point(s) |
NTD:
•Proportion of responders, where responders are defined as subjects who achieve an increase in Hgb ≥1.0 g/dL from pre-treatment baseline without transfusion, confirmed by a successive measurement at least 1 week later
•Hgb change from pre-treatment baseline
TD:
•Subjects who achieve a ≥20% reduction in the red blood cell (RBC) units transfused over an 8 week period compared to pre-treatment baseline
•Change from pre-treatment baseline in the number of units of RBC required
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
NTD subjects: every 4 weeks until subject responds or reaches the maximum dose of 80 mg weekly.
TD subjects: every 8 weeks until subject responds or reaches the maximum dose of 80 mg weekly.
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E.5.2 | Secondary end point(s) |
NTD:
•Proportion of subjects who achieve an increase in Hgb ≥1.5 g/dL from pre-treatment baseline without transfusion, confirmed by a successive measurement at least 1 week later
•Proportion of subjects who achieve a maintenance dose (defined in Study Design and Plan)
•Hgb level
•Duration of Hgb change of ≥1.0 g/dL from pre-treatment baseline without transfusion
•Duration of Hgb change of ≥1.5 g/dL from pre-treatment baseline without transfusion
•Change from pre-treatment 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
•Proportion of subjects who achieve a maintenance dose (defined in Study Design and Plan)
•Duration of response (defined as ≥ 20% reduction in the RBC units required over an 8-week period)
•Number of RBC units required
•Percent change from pre-treatment baseline in the RBC units required.
•Hgb level
•Hgb change from pre-treatment baseline
•Hgbchange from pre-treatment baseline
•Change from baseline in the following PD parameters: serum iron, ferritin, TSAT
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
NTD subjects: The first two endpoints are evaluated every 4 weeks until the subject meets the endpoint or reaches the maximum dose of 80 mg weekly. The other endpoints are evaluated at Month 24.
TD subjects: The first two endpoints are evaluated every 8 weeks until the subject meets the endpoint or reaches the maximum dose of 80 mg weekly. The other endpoints are evaluated at Month 24. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Greece |
Italy |
Lebanon |
Malaysia |
Thailand |
Tunisia |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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When all subjects have completed all study assessments or withdrawn early. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 24 |