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Trial details
Trial details
A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects with Chronic Anemia
Current status:
Approved
|
Date registered:
26/03/2019
Trial version(s)
History: 02/01/2019
Current: 02/01/2019
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2019020179
Protocol number
PTG300-02
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
01/02/2019
Primary sponsor
Protagonist Therapeutics Inc
Primary sponsor: Country of origin
USA
Public title
A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects with Chronic Anemia
Acronym
Scientific title
A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects with Chronic Anemia
Acronym
Brief summary of the study: English
This is a Phase 2 open-label, single-arm study with dose escalation by subject cohort and with the potential for individual titration (dose increase or decrease) within each cohort. The primary objectives of the study is to evaluate the safety and tolerability of PTG-300 in subjects with Non-Transfusion Dependent (NTD) and Transfusion Dependent (TD) β-thalassemia. To obtain preliminary evidence of to obtain preliminary evidence of PTG-300’s efficacy for treating chronic anemia in subjects with β-thalassemia and to identify the optimal starting dose, titration algorithm, dose range and dose regimen to be used in Phase 3 studies.
Brief summary of the study: Arabic
دراسة مرحلة 2 فتح التسمية، وذراع واحد مع تصعيد الجرعة حسب الفئات الموضوع وإمكانية معايرة الفردية داخل كل فئة. أهداف الرئيسية لهذه الدراسة تقييم السلامة وقابليةالتحمل .المصابون بمرض بيتا ثلاسيميا المعتمد على نقل الدم و غير المعتمد على نقل الدم PTG-300 لعلاج .
Health conditions/problem studied: Specify
Chronic anemia due to ineffective erythropoiesis (IE) in subjects with β thalassemia
Interventions: Specify
Five PTG-300 dose levels/regimens are planned to be tested for each subpopulation of β 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-<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
Key inclusion and exclusion criteria: Inclusion criteria
All subjects must meet ALL of the following inclusion criteria to be enrolled: 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. 4. 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. 5. 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. 6. 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. 7. Subjects, or legal representative (in the case of minors), are willing and able to adhere to the study visit schedule and other protocol requirements. 8. 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 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 randomization with no transfusion free period > 45 days. 2. Last RBC transfusion 5–10 days prior to dosing.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
12
Key inclusion and exclusion criteria: Age maximum
65
Key inclusion and exclusion criteria: Exclusion criteria
Subjects must meet NONE of the following exclusion criteria to be enrolled: 1. Subjects with the diagnosis of β-thalassemia major (genotype homozygous β0/β0 or compound heterozygous β0/β+ with a major phenotype). 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) or direct bilirubin > 1.5 x ULN 7. Treatment with hydroxyurea ≤ 24 weeks prior to randomization. 8. Use of erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization. 9. Chronic use of systemic glucocorticoids (anti-inflammatory dose for more than 14 days) ≤ 12 weeks prior to randomization (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.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
N/A: Single arm study
Study design: Masking
Open (masking not used)
Study design: Control
Dose comparison
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
No
Name of IMP
PTG-300
Type of IMP
Cell therapy
Pharmaceutical class
PTG-300 is a peptidic agent structurally related to natural hepcidin that mimics its inhibitory activity on ferroportin.
Therapeutic indication
β thalassemia
Therapeutic benefit
Administration of PTG-300 may result in iron redistribution in β-thalassemia subjects with potentially beneficial effects on erythropoiesis and consequently improvements in chronic anemia. This improvement in ineffective erythropoiesis may result in a clinical benefit both in NTD and in TD β-thalassemia subjects, by improving the symptomatology of the chronic anemia and the complications of the extramedullary hematopoiesis in the first group and by decreasing the need for transfusions in the latter.
Biospecimen retention
Samples without DNA
Biospecimen description
Blood samples taken throughout the study will be shipped to ICON lab in Ireland for analysis. These samples will be then stored at ICON Lab by Protagonist Therapeutics for up to 10 years.
Target sample size
84
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
11/03/2019
Date of study closure: Type
Anticipated
Date of study closure: Date
21/07/2020
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Patients' full identity will not be on any of the study documents or samples collected and kept by the sponsor for their studies. The full or partial date of birth will only be collected if medically relevant to this study. Only a unique participant number for the study will link the data or samples to the patients. These data may contain your gender and race, as well as any medical and scientific data required by the study.
Additional data URL
none
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Food and Drug Administration
IND 137605
Sources of Monetary or Material Support
Name
Protagonist Therapeutics.inc
Secondary Sponsors
Name
Not applicable
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT-CRO, Berytech Technology and Health, 5th Floor Damascus Road, Beirut, Lebanon
Lebanon
009611612500
zog_az@mct-cro.com
Regional Manager
Scientific
Ali
Taher
Chronic Care Center, Hazmieh, Lebanon
Lebanon
009613755669
ataher@aub.edu.lb
PI
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Chronic Care Center
Dr. Ali Taher
Professor of Medicine, Hematology & Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Chronic Care Center
02/12/2018
Michele Abi Saad
cccmas@chroniccare.org.lb
05-455101
American University of Beirut Medical Center
18/02/2019
Dr. Deborah Mukherji
irb@aub.edu.lb
01-350000 ext 5445
Countries of Recruitment
Name
Lebanon
Thailand
United Kingdom
United States of America
Turkey
Tunisia
Malaysia
Greece
Italy
Health Conditions or Problems Studied
Condition
Code
Keyword
Thalassemia
Thalassaemia (D56)
Thalassemia
Interventions
Intervention
Description
Keyword
PTG300
3mg subcutaneous (SC) weekly (n = 6 subjects per subpopulation)
Cohort 1
PTG300
10mg SC weekly (n = 6 subjects per subpopulation)
Cohort 2
PTG300
20mg SC weekly (n = 6 subjects per subpopulation)
Cohort 3
PTG300
40mg SC weekly (n = 6 subjects per subpopulation)
Cohort 4a
PTG300
40mg SC every 2 weeks (n = 6 subjects per subpopulation)
Cohort 4b
Primary Outcomes
Name
Time points
Measure
NTD patients: Mean Hgb change from baseline
4-week period under the same dose
Hemoglobin test at each dose
NTD subjects who achieve an increase in Hgb ≥ 1.0 g/dL without transfusion
4-week period under the same dose.
Hemoglobin test at each dose
TD Patients: achieve ≥ 20% reduction in the RBC units required over an 8 week period
8 week period
RBC units transfused
TD patients: Mean change from baseline in the number of units of RBC required under each dose
8 week period
RBC units transfused
Key Secondary Outcomes
Name
Time points
Measure
NTD patients: Mean Hgb
at the end of treatment
Hgb test
Proportion of subjects who achieve an increase in Hgb ≥ 1.5 g/dL
at any time up to Week 12 in NTD
Hgb test
Duration of response
NTD: Hgb change of ≥1 g/dL without transfusion; or ≥ 20% reduction in the RBC units required over an 8 week period in TD patients
Hbg test in NT; RBC units transfused in TD
Time to response
Hgb change of ≥1 g/dL without transfusion in NTD or ≥ 20% reduction in the RBC units required over an 8 week period in TD
Hbg test in NT; RBC units transfused in TD
TD patients: Mean number of RBC units required
at each dose over the 16 week period
RBC units transfused
Change from baseline in liver iron content
Week 16 for TD or week 12 for NTD
LIC measured by MRI
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial