A clinical study to evaluate the safety and effect of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) ß-Thalassemia Patients with Chronic Anemia.
- Conditions
- ß-Thalassemia Subjects with Chronic Anemia (transfusion and non transfusion dependent)MedDRA version: 20.0Level: PTClassification code 10043391Term: Thalassaemia betaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2018-001984-21-GB
- Lead Sponsor
- Protagonist Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 192
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 ß-thalassemia.
4. Documented diagnosis of ß-thalassemia with no other Hgb abnormality.
5. Women of childbearing potential (WOCBP) and men agree to use a highly effective contraceptive measure (based on the Clinical Trial Facilitation Group [CTFG]) during the duration of the study and for 28 days 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, as described in Appendix 1.
6. For WOCBP, a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to the first dose of study medication.
7. 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.
8. Subjects, or legal representative (in the case of minors), are willing and able to adhere to the study visit schedule and other protocol requirements.
9. Subjects between 12-<18 years of age understand and provide the assent to participate in the study, according to local guidelines.
Inclusion criteria applicable only for NTD ß-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 ß-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 5–15 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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method