Study of PTG-300 in Non-Transfusion Dependent and Transfusion-Dependent Beta-Thalassemia Subjects With Chronic Anemia

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

Sponsors

Lead Sponsor: Protagonist Therapeutics, Inc.

Source Protagonist Therapeutics, Inc.
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

Overall Status Completed
Start Date December 19, 2018
Completion Date June 13, 2020
Primary Completion Date June 13, 2020
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
NTD: Proportion of responders at each dose 4 week period
TD: Proportion of clinical responders at each dose 8 week period
Enrollment 63
Condition
Intervention

Intervention Type: Drug

Intervention Name: PTG-300

Description: Subcutaneous (SC)

Arm Group Label: PTG-300

Other Name: PTG-300 Active

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.

Gender: All

Minimum Age: 12 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Location
Facility:
UCSF Benioff Children's Hospital | Oakland, California, 94609, United States
Boston Children's Hospital | Boston, Massachusetts, 02115, United States
Hospital of The University of Pennsylvania | Philadelphia, Pennsylvania, 19104, United States
University General Hospital of Patras | Patras, Achaia, Greece
Laiko General Hospital of Athens | Athens, Attiki, 11562, Greece
Athens General Hospital 'G Gennimatas' | Athens, Attiki, Greece
Hippokration Hospital | Thessaloníki, Greece
Presidio Ospedaliero Antonio Perrino | Brindisi, 72100, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milano, 20122, Italy
AOU dell'Università degli Studi della Campania Luigi Vanvitelli | Napoli, 80138, Italy
Chronic Care Center | Beirut, Lebanon
Hospital Ampang | Ampang, 68000, Malaysia
Hospital Pulau Pinang | George Town, 10990, Malaysia
Hospital Sultanah Aminah | Johor Bahru, 80100, Malaysia
Queen Elizabeth Hospital | Kota Kinabalu, 88586, Malaysia
Hospital Umum Sarawak | Kuching, 93586, Malaysia
Chulalongkorn University | Bangkok, 10330, Thailand
Siriraj Hospital Mahidol University | Bangkok, 10700, Thailand
Maharaj Nakorn Chiang Mai Chiang Mai University | Chiang Mai, 50200, Thailand
Khon Kaen University | Khon Kaen, 40002, Thailand
Naresuan University | Phitsanulok, 65000, Thailand
University Hospital Farhat Hached | Sousse, 4000, Tunisia
Bone Marrow Transplant Center | Tunis, 1006, Tunisia
Aziza Othmana Hospital | Tunis, 1008, Tunisia
Principal Military Hospital | Tunis, 1089, Tunisia
Acibadem Adana Hospital | Adana, 01130, Turkey
Hacettepe University Medical Faculty | Ankara, 06100, Turkey
Akdeniz Universitesi Hastanesi | Antalya, 07059, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi | Istanbul, 34093, Turkey
Ege Universitesi Tip Fakultesi | Izmir, 35100, Turkey
Mersin University Medical Facult | Mersin, 33343, Turkey
Barts Health NHS Trust | London, E1 1BB, United Kingdom
Barts Health NHS Trust | London, United Kingdom
Location Countries

Greece

Italy

Lebanon

Malaysia

Thailand

Tunisia

Turkey

United Kingdom

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: PTG-300

Type: Experimental

Description: PTG-300 Active

Acronym TRANSCEND
Study Design Info

Intervention Model: Sequential Assignment

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

Masking: None (Open Label)

Source: ClinicalTrials.gov