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

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ClinicalTrials.gov Identifier: NCT04364269
Recruitment Status : Not yet recruiting
First Posted : April 28, 2020
Last Update Posted : May 19, 2020
Sponsor:
Collaborator:
Covance
Information provided by (Responsible Party):
Vifor (International) Inc.

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).

Condition or disease Intervention/treatment Phase
Beta-Thalassemia Drug: VIT-2763 once a day (QD) Drug: VIT-2763 twice a day (BID) Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multiple dose, multicentre, double-blind, placebo-controlled parallel group study in adult and adolescent male and female subjects with NTDT.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
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
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arm Intervention/treatment
Experimental: 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.

Drug: 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.

Experimental: 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.
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.

Placebo Comparator: Placebo
Participants will be assigned to receive Placebo, Twice a day.
Drug: Placebo
Participants will receive hard capsules of Placebo, twice a day.




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From baseline to Week 16 ]
    Reported or observed TEAEs by severity and relation to study product in each treatment group.

  2. Change in the Haemoglobin (Hb) level from baseline over a 12-week period [ Time Frame: From baseline to Week 12 ]
    Unit: g/dL

  3. Changes in the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: From baseline to Week 12 ]
    Summary of the values by visit from baseline and changes from baseline by post-baseline visit (Unit: mmHg)

  4. Changes in the heart rate [ Time Frame: From baseline to Week 12 ]
    Summary of the values by visit from baseline and changes from baseline by post-baseline visit (Unit: bpm)

  5. Changes in 12-lead electrocardiogram (ECG) parameters [ Time Frame: From baseline to Week 12 ]
    Values by visit from baseline and changes from baseline by post-baseline visit for PR interval, QRS duration, QT interval and QTcF interval


Secondary Outcome Measures :
  1. Change from baseline in total serum iron [ Time Frame: From baseline to Week 12 ]
    Assessment of total serum iron from baseline over a 12-week period (absolute and change from baseline)

  2. Change from baseline in serum ferritin [ Time Frame: From baseline to Week 12 ]
    Assessment of serum ferritin from baseline over a 12-week period (absolute and change from baseline)

  3. Change from baseline in serum transferrin [ Time Frame: From baseline to Week 12 ]
    Assessment of serum transferrin from baseline over a 12-week period (absolute and change from baseline)

  4. Change from baseline in calculated transferrin saturation (TSAT) [ Time Frame: From baseline to Week 12 ]
    Assessment of TSAT from baseline over a 12-week period (absolute and change from baseline)

  5. Pharmacokinetics parameters: individual estimated maximum concentration (Cmax) [ Time Frame: Baseline, Week 4, Week 8 and Week 12 ]
  6. Pharmacokinetics parameters: Clearance [ Time Frame: Baseline, Week 4, Week 8 and Week 12 ]
  7. Pharmacokinetics parameters: distribution volume [ Time Frame: Baseline, Week 4, Week 8 and Week 12 ]
  8. Pharmacokinetics parameters: Area under the curve (AUC) [ Time Frame: Baseline, Week 4, Week 8 and Week 12 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 2 consecutive measurements with at least 1 week apart within 6 weeks prior to randomisation/baseline, and obtained Hb values show less than 10 percent (%) relative difference (and equal or less than 1.0 g/dl absolute change between the highest and lowest value) between at least 2 measurements.

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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04364269


Contacts
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Contact: Vifor Pharma Management Ltd. Communications +41 588 518 000 info@viforpharma.com

Sponsors and Collaborators
Vifor (International) Inc.
Covance
Investigators
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Study Director: Frank Richard, MD Vifor Pharma Management Ltd.
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Responsible Party: Vifor (International) Inc.
ClinicalTrials.gov Identifier: NCT04364269    
Other Study ID Numbers: VIT-2763-THAL-201
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn