ENROLLING_BY_INVITATION

The BENeFiTS Trial in Beta Thalassemia Intermedia

Conditions

Beta Thalassemia Intermedia Sickle Cell Disease Non-transfusion dependent beta thalassemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Beta-thalassemias and hemoglobinopathies are serious inherited blood diseases caused by abnormal or deficiency of beta A chains of hemoglobin, the protein in red blood cells which delivers oxygen throughout the body.The diseases are characterized by hemolytic anemia, organ damage, and early mortality without treatment. Increases in another type of (normal) hemoglobin, fetal globin (HbF), which is normally silenced in infancy, reduces anemia and morbidity. Even incremental augmentation of fetal globin is established to reduce red blood cell pathology, anemia, certain complications, and to improve survival. This trial will evaluate an oral drug discovered in a high throughput screen, which increases fetal globin protein (HbF and red blood cells expressing HbF)and messenger ribonucleic acid (mRNA) to high levels in anemic nonhuman primates and in transgenic mice. The study drug acts by suppressing 4 repressors of the fetal globin gene promoter in progenitor cells from patients. The drug has been used for 50 years in a combination product for different actions - to enhance half-life and reduce side effects of a different active drug- and is considered safe for long-term use. This trial will first evaluate 3 dose levels in small cohorts of nontransfused patients with beta thalassemia intermedia. The most active dose will then be evaluated in larger subject groups with beta thalassemia and other hemoglobinopathies, such as sickle cell disease.

Official Title

A Phase 1b Sequential Open Label Dose-Ranging Study of Safety, Pharmacokinetics, and Preliminary Activity of Benserazide in Subjects With Beta Thalassemia Intermedia and Sickle Cell Disease

Quick Facts

Study Start:2020-10-05

Study Completion:2026-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ENROLLING_BY_INVITATION

Study ID

NCT04432623

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Beta thalassemia intermedia (BTI) or (NTDT, Non-Transfusion Dependent Thalassemia) with at least one documented beta thalassemia mutation, including HbE beta thalassemia or an established diagnosis of sickle cell disease * \>18 years of age at time of consent * Average of 2 total hemoglobin (Hgb) levels between 6.0 and 10.0 g/dL in the preceding 6 months * Able and willing to give consent and comply with all study procedures * If female and of childbearing potential, must have a documented negative pregnancy test prior to entry and agree to use one or more locally medically accepted methods of contraception	* Red blood cell (RBC) transfusion within 2 months prior to administration of study medication * Participating in a chronic transfusion program * Pulmonary hypertension requiring oxygen therapy * Use of erythropoiesis stimulating agents within 90 days of first dose * Transaminases \> 3 times upper limit of institution normal (ULN) * Total and direct bilirubin \> 3 times institution ULN unless due solely to hemolysis * Known infection with HIV or hepatitis C (untreated) * Fever \> 38.5°C in the week prior to first administration of study medication * History of osteoporosis or osteomalacia with a fragility fracture * Received other investigational systemic therapy within 30 days prior to first dose * Narrow angle glaucoma * Currently pregnant or breast feeding a child * Known current drug or alcohol abuse * Taking monoamine oxidase inhibitors * Other co-morbidity that substantially increases subject risk for the study per Investigator discretion

Inclusion Criteria

Exclusion Criteria

* Beta thalassemia intermedia (BTI) or (NTDT, Non-Transfusion Dependent Thalassemia) with at least one documented beta thalassemia mutation, including HbE beta thalassemia or an established diagnosis of sickle cell disease
* \>18 years of age at time of consent
* Average of 2 total hemoglobin (Hgb) levels between 6.0 and 10.0 g/dL in the preceding 6 months
* Able and willing to give consent and comply with all study procedures
* If female and of childbearing potential, must have a documented negative pregnancy test prior to entry and agree to use one or more locally medically accepted methods of contraception

* Red blood cell (RBC) transfusion within 2 months prior to administration of study medication
* Participating in a chronic transfusion program
* Pulmonary hypertension requiring oxygen therapy
* Use of erythropoiesis stimulating agents within 90 days of first dose
* Transaminases \> 3 times upper limit of institution normal (ULN)
* Total and direct bilirubin \> 3 times institution ULN unless due solely to hemolysis
* Known infection with HIV or hepatitis C (untreated)
* Fever \> 38.5°C in the week prior to first administration of study medication
* History of osteoporosis or osteomalacia with a fragility fracture
* Received other investigational systemic therapy within 30 days prior to first dose
* Narrow angle glaucoma
* Currently pregnant or breast feeding a child
* Known current drug or alcohol abuse
* Taking monoamine oxidase inhibitors
* Other co-morbidity that substantially increases subject risk for the study per Investigator discretion

Contacts and Locations

Principal Investigator

Susan Perrine, MD

STUDY_DIRECTOR

Phoenicia BioScience

Kevin Kuo, MD

PRINCIPAL_INVESTIGATOR

University Health Network, Toronto General Hospital

Sylvia Singer, MD

PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital at Oakland

Hanny D Al-Samkari, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Sujit Sheth, MD MS

PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Study Locations (Sites)

UCSF Benioff Children's Hospital at Oakland

Oakland, California, 94609

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Susan Perrine

Weston, Massachusetts, 02493

United States

Weil Cornell Medicine

New York, New York, 10065

United States

Collaborators and Investigators

Sponsor: Phoenicia BioScience

Susan Perrine, MD, STUDY_DIRECTOR, Phoenicia BioScience
Kevin Kuo, MD, PRINCIPAL_INVESTIGATOR, University Health Network, Toronto General Hospital
Sylvia Singer, MD, PRINCIPAL_INVESTIGATOR, UCSF Benioff Children's Hospital at Oakland
Hanny D Al-Samkari, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital
Sujit Sheth, MD MS, PRINCIPAL_INVESTIGATOR, Weill Medical College of Cornell University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-05

Study Completion Date2026-02-28

Study Record Updates

Study Start Date2020-10-05

Study Completion Date2026-02-28

Terms related to this study

Keywords Provided by Researchers

Non-transfusion dependent beta thalassemia
Sickle cell disease

Additional Relevant MeSH Terms

Beta Thalassemia Intermedia
Sickle Cell Disease