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

NCT03802201 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: PTG-300-02
• Study Type: interventional
• Target: 63
• Locations: 8 countries
• Sites: 27

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.

Conditions

β-thalassemia; Ineffective Erythropoiesis; Chronic Anemia

Keywords

chronic anemia; β-thalassemia

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

PTG-300 Active

EXPERIMENTAL

Drug: PTG-300 Subcutaneous

Drug: PTG-300

Interventions

PTG-300 DRUG

Subcutaneous (SC)

PTG-300 Active

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged 18 to 65 years, inclusive (Cohorts 1-4b).
• Male and female subjects aged 12-\<18 years, with a minimum weight of 30 kg (Cohorts 5 and 6).
• Documented diagnosis of β-thalassemia with no other Hgb abnormality.
• 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).
• Requirement of \< 6 units RBC transfusion in a 24 week period with the last transfusion at least 8 weeks before screening.
• Transfusion requirement of at least 6 units of RBC in the 24 weeks prior to screening with no transfusion free period \> 45 days.
• Last RBC transfusion 5-10 days prior to dosing.

You may not qualify if:

• Subjects with Sickle Cell disease, Hgb H, Hb Bart's hydrops foetalis or hemoglobin S
• 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).
• 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.
• Known primary or secondary immunodeficiency.
• 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).
• Pregnant or lactating females.

Sponsors & Collaborators

• Protagonist Therapeutics, Inc.: lead

Study Sites (33)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Hospital of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University General Hospital of Patras

Pátrai, Achaia, Greece

Location

Laiko General Hospital of Athens

Athens, Attica, 11562, Greece

Location

Athens General Hospital 'G Gennimatas'

Athens, Attica, Greece

Location

Hippokration Hospital

Thessaloniki, Greece

Location

Presidio Ospedaliero Antonio Perrino

Brindisi, 72100, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

AOU dell'Università degli Studi della Campania Luigi Vanvitelli

Napoli, 80138, Italy

Location

Chronic Care Center

Beirut, Lebanon

Location

Hospital Ampang

Ampang, 68000, Malaysia

Location

Hospital Pulau Pinang

George Town, 10990, Malaysia

Location

Hospital Sultanah Aminah

Johor Bahru, 80100, Malaysia

Location

Queen Elizabeth Hospital

Kota Kinabalu, 88586, Malaysia

Location

Hospital Umum Sarawak

Kuching, 93586, Malaysia

Location

Chulalongkorn University

Bangkok, 10330, Thailand

Location

Siriraj Hospital Mahidol University

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Naresuan University

Phitsanulok, 65000, Thailand

Location

University Hospital Farhat Hached

Sousse, 4000, Tunisia

Location

Bone Marrow Transplant Center

Tunis, 1006, Tunisia

Location

Aziza Othmana Hospital

Tunis, 1008, Tunisia

Location

Principal Military Hospital

Tunis, 1089, Tunisia

Location

Acibadem Adana Hospital

Adana, 01130, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Akdeniz Universitesi Hastanesi

Antalya, 07059, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

Istanbul, 34093, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35100, Turkey (Türkiye)

Location

Mersin University Medical Facult

Mersin, 33343, Turkey (Türkiye)

Location

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

Barts Health NHS Trust

London, United Kingdom

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 14, 2019
• Study Start: December 19, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: July 16, 2021

Record last verified: 2021-07

Locations

MY (5); LE (1); IT (3); US (3); TU (4); GB (2); GR (4); TH (5)