Clinical trial NCT04364269: Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD) and Preliminary Efficacy of VIT-2763 in β-thalassaemia
Official title: A Phase 2a, Double-blind, Randomised, Placebo-controlled, Parallel Group, Multicentre Study on Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Multiple Doses of VIT-2763 in Subjects With Non-transfusion Dependent β-thalassaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Beta-Thalassemia
Non-transfusion-dependent Thalassemia
Keywords: Beta-Thalassemia
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
Collaborators: name: Labcorp Corporation of America Holdings, Inc
First posted: 2020-04-28
Enrollment: 35
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multiple dose, multicenter, double-blind, placebo-controlled parallel group study in adult and adolescent male and female subjects with non-transfusion dependent thalassemia (NTDT)
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From baseline to Week 16
measure: Changes in the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: From baseline to Week 12
measure: Changes in the Heart Rate
timeFrame: From baseline to Week 12
measure: Changes in 12-lead Electrocardiogram (ECG) Parameters
timeFrame: From baseline to Week 12
Secondary outcomes:
measure: Change From Baseline in Total Serum Iron
timeFrame: From baseline to Week 12
measure: Change From Baseline in Serum Ferritin
timeFrame: From baseline to Week 12
measure: Change From Baseline in Serum Transferrin
timeFrame: From baseline to Week 12
measure: Change From Baseline in Calculated Transferrin Saturation (TSAT) )
timeFrame: From baseline to Week 12
measure: Pharmacokinetics Parameters - VIT-2763 Plasma Concentration Over Time
timeFrame: Baseline, Week 4, Week 8 and Week 12
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Clinical Site #301
state: Attiki
city: Rio
country: Greece
facility: Clinical Site #302
city: Thessaloniki
country: Greece
facility: Clinical Site #303
city: Afula
country: Israel
facility: Clinical Site #401
city: Haifa
country: Israel
facility: Clinical Site #402
city: Petah Tikva
country: Israel
facility: Clinical Site #403
city: Milan
country: Italy
facility: Clinical Site #201
state: MI
city: Napoli
country: Italy
facility: Clinical Site #203
city: Napoli
country: Italy
facility: Clinical Site #206
city: Orbassano
country: Italy
facility: Clinical Site #207
city: Palermo
country: Italy
facility: Clinical Site #205
city: Verona
country: Italy
facility: Clinical Site #202
city: Beirut
country: Lebanon
facility: Clinical Site #101
city: Bangkok
country: Thailand
facility: Clinical Site #501
city: Chiang Mai
country: Thailand
facility: Clinical Site #502
city: Phitsanulok
country: Thailand
facility: Clinical Site #503
Study officials:
affiliation: Vifor (International) Inc.
name: Clinical Research Department
role: STUDY_DIRECTOR
References: