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

NCT ID: NCT04364269

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-11
• Study Completion Date: 2021-11-03

Brief 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).

Detailed Description

The study includes a 12-week treatment period and a safety follow-up period of 4 weeks.

About 36 participants (adults and adolescents) are expected to take part in this study at a number of different institutions internationally.

Adult Participants (Cohort I) will be randomized to receive either VIT-2763 once daily (QD) or twice daily (BID) or placebo, at a dose of 120 mg or 60mg depending on their body weight. Following cohort I review, adolescent participants (Cohort II) will be randomized to the same study arms with the same interventions.

The study medication will be given as oral capsules, containing 60 mg of VIT-2763 or placebo.

Conditions

Beta-Thalassemia; Non-transfusion-dependent Thalassemia

Keywords

Beta-Thalassemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

VIT-2763 Once a day (QD)

Participants will be assigned to receive VIT-2763 once a day (QD) in a total daily dose of 60 mg or 120 mg depending on their body weight.

The study medication (VIT-2763 and/or matching placebo) will be administered for all participants twice a day to maintain the blind.

Group Type: EXPERIMENTAL

VIT-2763 once a day (QD)

Intervention Type: DRUG

Participants will receive VIT-2763 QD at a dose of 60 mg if their body weight is between 40 kg to 59 kg or at a dose of 120 mg if their body weight is between 60 kg and 100 kg, during 12 weeks.

VIT-2763 Twice a day (BID)

Participants will be assigned to receive VIT-2763 Twice a day (BID) in a total daily dose of 60 mg or 120 mg depending on their body weight.

Group Type: EXPERIMENTAL

VIT-2763 twice a day (BID)

Intervention Type: DRUG

Participants will receive VIT-2763 BID at a dose of 60 mg if their body weight is between 40 kg to 59 kg or at a dose of 120 mg if their body weight is between 60 kg and 100 kg, during 12 weeks.

Placebo

Participants will be assigned to receive Placebo, Twice a day.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive hard capsules of Placebo, twice a day.

Interventions

VIT-2763 once a day (QD)

Participants will receive VIT-2763 QD at a dose of 60 mg if their body weight is between 40 kg to 59 kg or at a dose of 120 mg if their body weight is between 60 kg and 100 kg, during 12 weeks.

Intervention Type: DRUG

VIT-2763 twice a day (BID)

Participants will receive VIT-2763 BID at a dose of 60 mg if their body weight is between 40 kg to 59 kg or at a dose of 120 mg if their body weight is between 60 kg and 100 kg, during 12 weeks.

Intervention Type: DRUG

Placebo

Participants will receive hard capsules of Placebo, twice a day.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Labcorp Corporation of America Holdings, Inc

INDUSTRY

Sponsor Role: collaborator

Vifor (International) Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Research Department

Role: STUDY_DIRECTOR

Vifor (International) Inc.

Locations

Clinical Site #301

Athens, Attica, Greece

Clinical Site #302

Rio, , Greece

Clinical Site #303

Thessaloniki, , Greece

Clinical Site #401

Afula, , Israel

Clinical Site #402

Haifa, , Israel

Clinical Site #403

Petah Tikva, , Israel

Clinical Site #201

Milan, MI, Italy

Clinical Site #203

Napoli, , Italy

Clinical Site #206

Napoli, , Italy

Clinical Site #207

Orbassano, , Italy

Clinical Site #205

Palermo, , Italy

Clinical Site #202

Verona, , Italy

Clinical Site #101

Beirut, , Lebanon

Clinical Site #501

Bangkok, , Thailand

Clinical Site #502

Chiang Mai, , Thailand

Clinical Site #503

Phitsanulok, , Thailand

Countries

Greece; Israel; Italy; Lebanon; Thailand

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002221-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VIT-2763-THAL-201

Identifier Type: -

Identifier Source: org_study_id