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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Anemia; β-thalassemia; Ineffective Erythropoiesis
• Intervention / Treatment: Drug: PTG-300

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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTG-300 Active; Drug: PTG-300 Subcutaneous	Drug: PTG-300; Subcutaneous (SC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NTD: Proportion of responders at each dose	NTD subjects who achieve an increase in Hgb without transfusion	4 week period
TD: Proportion of clinical responders at each dose	TD subjects who achieve a reduction in red blood cell (RBC) units required over an 8 week period	8 week period

Collaborators and Investigators

• Sponsor: Protagonist Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: β-thalassemia; chronic anemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: PTG-300-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No