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

NCT04364269 | Completed Phase 2 Results

• 2 other identifiers: VIT-2763-THAL-2012019-002221-29
• Study Type: interventional
• Target: 35
• Locations: 5 countries
• Sites: 16

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).

Conditions

Beta-Thalassemia; Non-transfusion-dependent Thalassemia

Keywords

Beta-Thalassemia

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Please note that in this section we are presenting just the overview of the adverse events experienced by the trial participants, in particular, the number of participants with at least one TEAE. Please refer to the detailed tables included on the Adverse Event Module for specifics.

  From baseline to Week 16

• Changes in the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Summary of the values by visit from baseline and changes from baseline by post-baseline visit.

  From baseline to Week 12

• Changes in the Heart Rate

  Summary of the values by visit from baseline and changes from baseline by post-baseline visit.

  From baseline to Week 12

• Changes in 12-lead Electrocardiogram (ECG) Parameters

  Values by visit from baseline and changes from baseline by post-baseline visit. The following ECG parameters were recorded: PR interval, QRS duration, QT interval, RR interval and QTcF interval. PR interval represents the time from the onset of the P wave to the start of the QRS complex. QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). QT interval represents the time from the start of the Q wave to the end of the T wave. RR interval represents the time from the onset of one R wave to the onset of the next one, one complete cardiac cycle. QT corrected for heart rate (QTc) interval reflects ventricular repolarization.

  From baseline to Week 12

Secondary Outcomes (5)

• Change From Baseline in Total Serum Iron

  From baseline to Week 12

• Change From Baseline in Serum Ferritin

  From baseline to Week 12

• Change From Baseline in Serum Transferrin

  From baseline to Week 12

• Change From Baseline in Calculated Transferrin Saturation (TSAT) )

  From baseline to Week 12

• Pharmacokinetics Parameters - VIT-2763 Plasma Concentration Over Time

  Baseline, Week 4, Week 8 and Week 12

Study Arms (3)

VIT-2763 Once a day (QD)

EXPERIMENTAL

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.

Drug: VIT-2763 once a day (QD)

VIT-2763 Twice a day (BID)

EXPERIMENTAL

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.

Drug: VIT-2763 twice a day (BID)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

VIT-2763 once a day (QD) 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 Once a day (QD)

VIT-2763 twice a day (BID) 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.

VIT-2763 Twice a day (BID)

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vifor (International) Inc.: lead
• Labcorp Corporation of America Holdings, Inc: collaborator

Study Sites (16)

Clinical Site #301

Athens, Attica, 115 27, Greece

Location

Clinical Site #302

Rio, 265 04, Greece

Location

Clinical Site #303

Thessaloniki, 54642, Greece

Location

Clinical Site #401

Afula, 18411, Israel

Location

Clinical Site #402

Haifa, 34362, Israel

Location

Clinical Site #403

Petah Tikva, 49100, Israel

Location

Clinical Site #201

Milan, MI, 20122, Italy

Location

Clinical Site #203

Napoli, 80131, Italy

Location

Clinical Site #206

Napoli, 80138, Italy

Location

Clinical Site #207

Orbassano, 10043, Italy

Location

Clinical Site #205

Palermo, 90146, Italy

Location

Clinical Site #202

Verona, 37134, Italy

Location

Clinical Site #101

Beirut, 11-0236b, Lebanon

Location

Clinical Site #501

Bangkok, 10700, Thailand

Location

Clinical Site #502

Chiang Mai, 50200, Thailand

Location

Clinical Site #503

Phitsanulok, 65000, Thailand

Location

Related Publications (1)

• Kattamis A, Taher A, Viprakasit V, Levin C, Hermosilla R, Szecsody P, Richard F, Cappellini MD, Porter J. Safety and pharmacodynamics of the ferroportin inhibitor vamifeport in patients with non-transfusion-dependent beta-thalassemia: results from a randomized phase 2a study. Orphanet J Rare Dis. 2025 Nov 25;20(1):608. doi: 10.1186/s13023-025-04119-y.

  PMID: 41291806 DERIVED

MeSH Terms

Conditions

beta-Thalassemia

Interventions

BID protein, human

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

Results Point of Contact

• Title: CSL Vifor
• Organization: Vifor Pharma, Inc.

VIT2763-THAL-201.study@viforpharma.com

+41 588 518 000

Study Officials

• Clinical Research Department

  Vifor (International) Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will receive a randomisation number using a validated centralised procedure (IWRS) that automates the random assignment of treatment groups to randomisation numbers. The randomisation plan will be kept strictly confidential, accessible only to authorised persons, until the time of unblinding. The study drugs (VIT-2763 or placebo) are provided in identical white opaque hard capsules in packaging of identical appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple dose, multicenter, double-blind, placebo-controlled parallel group study in adult and adolescent male and female subjects with non-transfusion dependent thalassemia (NTDT)

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 28, 2020
• Study Start: June 11, 2020
• Primary Completion: October 11, 2021
• Study Completion: November 3, 2021
• Last Updated: December 14, 2023
• Results First Posted: December 14, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (3); GR (3); LE (1); TH (3); IT (6)