Overview

Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Preliminary Efficacy of VIT-2763 in β-thalassaemia

Status:
Active, not recruiting
Trial end date:
2021-11-01
Target enrollment:
0
Participant gender:
All
Summary
This is a randomised, double-blind, placebo-controlled parallel group trial to investigate the safety, tolerability and efficacy of multiple doses of VIT-2763 versus placebo in participants with non-transfusion-dependent Beta-thalassemia (NTDT).
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Vifor (International) Inc.
Collaborator:
Covance
Criteria
Inclusion Criteria:

- Documented diagnosis of NTDT, including a β-thalassemia intermedia-phenotype.

- NTDT is defined as subjects having received less than 5 units of red blood cells
(RBCs) during the 24-week period prior to randomisation/first drug administration of
VIT-2763 or placebo (Day 1; 1 unit is defined as 200 to 350 ml of transfused packed
RBCs and last RBC transfusion must have been received at east 14 days prior to
randomisation).

- Male and female adult NTDT subjects, 18-65 years of age inclusive (Cohort I only) at
time of screening.

- Male and female adolescent NTDT subjects, 12-17 years of age inclusive (Cohort II
only) at time of screening.

- Subjects must have a mean baseline hemoglobin (Hb) equal to or lower than 11 g/dl,
based on at least 2 consecutive measurements with at least 1 week apart within 6 weeks
prior to randomisation/baseline.

Exclusion Criteria:

- Documented diagnosis of transfusion dependent thalassemia (TDT), including a
beta-thalassemia major phenotype (including β0/β0, β+/β+, β0/β+ genotype), and mixed
compound heterozygous for sickling phenotype variants such as Hb S/β- thalassemia, or
transfusion dependent non-deletional Hb H disease (i.e., Hb constant spring) or Hb C
disease.

- Subjects on concomitant iron chelation therapy (ICT) or subjects on prior ICT when
discontinued less than 4 weeks prior randomisation. If ICT was discontinued at least 4
weeks prior randomization the subject is eligible.

- ICT naïve subjects or subjects who discontinued ICT therapy at least 6 months before
the screening visit with serum ferritin lower than 150 ng/ml and/or documented liver
iron concentration (LIC) equal to or lower than 1 mg/g liver dry weight assessed
through magnetic resonance imaging (MRI), or subjects on prior ICT with serum ferritin
lower than 300 ng/ml and/or documented LIC lower than 3 mg/g liver dry weight assessed
through MRI.

- Subjects with transferrin saturation (TSAT) less than 30%.

- Subjects with documented LIC greater than 15 mg/g liver dry weight assessed through
MRI, or a documented myocardial T2* less than 20 ms, if available per local practice
and retrieved within 24 months prior to randomization.

- Adult or adolescent subjects with body weight lower than 40.0 kg or greater than 100
kg at screening.

- Chronic liver disease and/or alanine transaminase (ALT), aspartate transaminase (AST)
or gamma-glutamyl transpeptidase (GGT) above 3-fold the upper limit of normal (ULN)
range at screening.

- Estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 (according to
chronic kidney disease classification Stage 4 or higher), and/or significant
albuminuria greater than 30 mg/mmol. eGFR should be estimated according to Chronic
Kidney Disease Epidemiology Collaboration formula (CKI-EPI) in adults, and Schwartz
formula in adolescents.

- Newly diagnosed folate deficiency anemia and/or Vitamin B12 megaloblastic anemia.
Subjects with known folate deficiency anemia and/or Vitamin B12 megaloblastic anemia
who are on at least 12 weeks stable replacement therapy are eligible.

- Any history or clinically important finding of cardiac disorders, such as clinically
relevant cardiac arrhythmia, cardiomyopathy, coronary disease, valve disorder, or
heart failure according to New York Heart Association classification 3-4.

- Subjects with history of partial or total splenectomy within 6 months prior to
screening.