The BENeFiTS Trial in Beta Thalassemia Intermedia

NCT04432623 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 2 other identifiers: PB04-001R33HL147845
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Beta Thalassemia Intermedia; Sickle Cell Disease

Keywords

Non-transfusion dependent beta thalassemia; Sickle cell disease

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  12 to 24 weeks

• Maximum plasma concentration (Cmax)

  drug concentration (ng/ml)

  4 weeks

• Plasma drug concentration over time

  Area under the curve

  4 weeks

Secondary Outcomes (4)

• F-cells

  12 to 24 weeks

• HbF protein per cell

  12 to 24 weeks

• Fetal hemoglobin (HbF)

  12 to 24 weeks

• Hemoglobin

  16 to 24 weeks

Study Arms (5)

Low dose

EXPERIMENTAL

A low dose, by mouth, once per day, on Monday, Wednesday, and Friday for 12 weeks

Drug: Benserazide Only Product

Middle dose

EXPERIMENTAL

A middle dose, by mouth, once per day, on Monday, Wednesday, and Friday, for 12 weeks

Drug: Benserazide Only Product

High dose 3 days per week

EXPERIMENTAL

Highest dose, by mouth, once per day, on Monday, Wednesday, and Friday, for 12 to 24 weeks

Drug: Benserazide Only Product

High dose 5 days per week

EXPERIMENTAL

The highest dose, by mouth once per day on 5 days per week for 24 weeks

Drug: Benserazide Only Product

Sickle Cell Disease Arm

EXPERIMENTAL

The most active dose given once per day on the most active regimen for up 24 weeks

Drug: Benserazide Only Product

Interventions

Benserazide Only Product DRUG

Investigational drug

High dose 3 days per week; High dose 5 days per week; Low dose; Middle dose; Sickle Cell Disease Arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Phoenicia BioScience: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

UCSF Benioff Children's Hospital at Oakland

Oakland, California, 94609, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Susan Perrine

Weston, Massachusetts, 02493, United States

Location

Weil Cornell Medicine

New York, New York, 10065, United States

Location

University Health Network and Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

Related Publications (33)

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MeSH Terms

Conditions

beta-Thalassemia; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Susan Perrine, MD

  Phoenicia BioScience

  STUDY DIRECTOR

• Kevin Kuo, MD

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

• Sylvia Singer, MD

  UCSF Benioff Children's Hospital at Oakland

  PRINCIPAL INVESTIGATOR

• Hanny D Al-Samkari, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Sujit Sheth, MD MS

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each higher dose level cohort will be enrolled after 2 weeks of treatment in the lower dose level. Additional doses or regimens may be added or expanded.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 16, 2020
• Study Start: October 5, 2020
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (4)