Summary

Eligibility
for people ages 18-45 (full criteria)
Location
at Oakland, California and other locations
Dates
study started
estimated completion
Principal Investigator
Sylvia Singer

Description

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. Increases in another type of (normal) hemoglobin, fetal globin (HbF), which is normally silenced in infancy, reduces the severity of both conditions. 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 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 thalassemia patients. The drug has been used for many years in a combination product for different actions - to enhance half-life and reduce side effects of an active drug- and is considered safe for chronic 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.

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

Details

The study will first evaluate 3 doses of the investigational drug which are considered safe with chronic use in a combination therapeutic used widely for a neurologic disease in Europe and Canada. The doses to be studied are human equivalent doses of doses that are active in nonhuman primates in inducing high level fetal globin messenger ribonucleic acid (mRNA), protein, and proportions of red blood cells expressing fetal globin protein (F-cells). Additive effects are observed with hydroxyurea in sickle cell patients' cells in vitro.

The study will first evaluate the study therapeutic in male and female patients who are 18 years and older. After a screening period to obtain baseline medical and laboratory data, the study drug will be taken by mouth once per day, every other day. The first dose will be taken in a clinical unit, and thereafter will be taken at home for 12 weeks. Laboratory tests, physical exams, and tolerability will be assessed 6 times over 4 months, including for one month after completion of dosing.

The cohorts will be enrolled sequentially. Each new cohort will begin after the prior lower dose cohort has received 2 weeks of treatment without serious adverse events related to the study drug. The dose that increases fetal globin assays to the highest degree will be evaluated in a larger group of subjects.Other regimens or test doses may be added as needed. The study drug is expected to be safe when added to most other medications.

Keywords

Beta Thalassemia Intermedia Sickle Cell Disease Non-transfusion dependent beta thalassemia Anemia, Sickle Cell Thalassemia beta-Thalassemia Benserazide Benserazide Only Product

Eligibility

You can join if…

Open to people ages 18-45

  • Beta thalassemia intermedia (BTI) or (NTDT, Non-Transfusion Dependent Thalassemia) with at least one documented beta thalassemia mutation, including HbE beta thalassemia
  • 18 to 45 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 CAN'T join 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
  • Creatinine clearance <75 mL/min/1.73 meter square (m2)
  • Splenomegaly with spleen palpable >4 cm below the left costal margin.
  • Known infection with HIV or hepatitis C (untreated)
  • Fever > 38.5°C in the week prior to first administration of study medication
  • Evidence of osteoporosis or osteomalacia
  • 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

Locations

  • UCSF Benioff Children's Hospital at Oakland
    Oakland California 94609 United States
  • University Health Network and Toronto General Hospital
    Toronto Ontario M5G2C4 Canada

Lead Scientist at UCSF

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Phoenicia BioScience
ID
NCT04432623
Phase
Phase 1/2
Study Type
Interventional
Last Updated