Clinical trial NCT03802201: Study of PTG-300 in Non-Transfusion Dependent and Transfusion-Dependent Beta-Thalassemia Subjects With Chronic Anemia
Official title: A Phase 2 Study of PTG-300 in Non-Transfusion Dependent (NTD) and Transfusion-Dependent (TD) β-Thalassemia Subjects With Chronic Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: β-thalassemia
Ineffective Erythropoiesis
Chronic Anemia
Keywords: chronic anemia
β-thalassemia
Lead sponsor: Protagonist Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 63
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Multiple PTG-300 dose levels/regimens are planned to be tested for each subpopulation of β thalassemia (NTD and TD) on separate arms:

* Cohort 1: 3 mg subcutaneous (SC) weekly
* Cohort 2: 10 mg SC weekly
* Cohort 3: 20 mg SC weekly
* Cohort 4a: 40 mg SC weekly
* Cohort 4b: 40 mg SC every 2 weeks
* Cohort 7: 80 mg SC weekly
* Cohort 8: 40 mg SC twice a week

Additional Cohorts (Cohorts 5,6,9,10, and 11) will include subjects between 12 years of age and less than 18 years of age.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: NTD: Proportion of responders at each dose
timeFrame: 4 week period
measure: TD: Proportion of clinical responders at each dose
timeFrame: 8 week period
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Hospital of The University of Pennsylvania
state: Pennsylvania
city: Patras
country: Greece
facility: University General Hospital of Patras
state: Achaia
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attiki
city: Athens
country: Greece
facility: Athens General Hospital 'G Gennimatas'
state: Attiki
city: Thessaloníki
country: Greece
facility: Hippokration Hospital
city: Brindisi
country: Italy
facility: Presidio Ospedaliero Antonio Perrino
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: AOU dell'Università degli Studi della Campania Luigi Vanvitelli
city: Beirut
country: Lebanon
facility: Chronic Care Center
city: Ampang
country: Malaysia
facility: Hospital Ampang
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
city: Kota Kinabalu
country: Malaysia
facility: Queen Elizabeth Hospital
city: Kuching
country: Malaysia
facility: Hospital Umum Sarawak
city: Bangkok
country: Thailand
facility: Chulalongkorn University
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Phitsanulok
country: Thailand
facility: Naresuan University
city: Sousse
country: Tunisia
facility: University Hospital Farhat Hached
city: Tunis
country: Tunisia
facility: Bone Marrow Transplant Center
city: Tunis
country: Tunisia
facility: Aziza Othmana Hospital
city: Tunis
country: Tunisia
facility: Principal Military Hospital
city: Adana
country: Turkey
facility: Acibadem Adana Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Mersin
country: Turkey
facility: Mersin University Medical Facult
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
Study officials:
References: