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

About the study

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.

Study point of contact

Melissa Askin, RN
410 231-1512
Susan Perrine, MD
617 335-7002


2 United States sites

1 Canada site


> 18 Years


Phase 1/Phase 2

Study type








participation requirements

– Beta thalassemia intermedia (BTI) or (NTDT, Non-Transfusion Dependent Thalassemia)
with at least one documented beta thalassemia mutation, including HbE beta thalassemia

– >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

participation restrictions

– Red blood cell (RBC) transfusion within 2 months prior to administration of study

– 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

– Creatinine clearance <75 mL/min/1.73 meter square (m2) - 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


  • Oakland, California, United States, UCSF Benioff Children's Hospital at Oakland, 94609 [Recruiting]
  • Weston, Massachusetts, United States, Susan Perrine, 02493 [Not yet recruiting]
  • Toronto, Ontario, Canada, University Health Network and Toronto General Hospital, M5G2C4 [Recruiting]
Last updated 2021-05-26