Efficacy and Safety Study of Multiple Doses of VIT-2763 in Adults With Transfusion-dependent Beta-thalassaemia

Phase 1

• Conditions: transfusiondependent ß-thalassaemia; MedDRA version: 22.0Level: LLTClassification code 10081911Term: Transfusion dependent thalassaemiaSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2021-001639-23-IT
• Lead Sponsor: VIFOR (INTERNATIONAL) INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-27
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Male or female gender.
2. 18 to 65 years of age at screening.
3. Body weight =40.0 kg and =100 kg at screening (adult male and female subjects).
4. Documented diagnosis of ß-thalassaemia or Hb E/ß-thalassaemia (ß thalassaemia with mutation and/or multiplication of a-globin is allowed).
5. RBC transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomisation and no transfusion-free period for =35 days during that period.
In order to verify RBC transfusion dependence, 12 weeks of transfusion history will be collected prospectively during the screening/run-in period, and 12 weeks of transfusion history will be collected retrospectively from subjects’ history. In those cases where sites have the transfusion records only in volumes (cc or ml), a conversion of volume to defined units will be performed, in order to obtain the number of units within the last24 weeks to assess the eligibility. Specifications how to convert RBC volumes to units are given in Section 5.2 of the protocol.
6. Ability to understand the requirements of the study, and abide by the study restrictions, and agreement to return for the required assessments.
7. Subject (and/or legally acceptable representative) must understand and has provided voluntarily the appropriate written informed consent using the Informed Consent Form (ICF). Subject must provide written informed consent before any study-specific procedures are performed including screening procedures, see Section 12.12.2 of the protocol.
8. Female subjects of childbearing potential must have a negative serum pregnancy test at screening confirmed by a negative urine pregnancy test at randomisation, must have stopped breastfeeding as of first dose, and must either commit to true abstinence from
heterosexual contact (which must be reviewed on a monthly basis and source documented) or must be willing to use adequate contraceptive precautions (i.e., highly effective method of birth control). Female subjects must agree to use adequate contraception during the study and for 1 month after the last dose of study medication or according to local requirements, whichever is longer. Effective contraception (highly effective method of birth control i.e., with a failure rate of <1% per year, when used consistently and correctly) such as implants, injectables, combined oral contraceptives, bilateral tubal occlusion, intrauterine devices, sexual abstinence, or vasectomised partner must be used. Non-childbearing potential includes being surgically sterilised at
least 6 months prior to the study.
Note: For female subjects participating in this study, continuous use of hormonal contraception alone is not sufficient, because potential interactions via cytochrome P450 (CYP) enzymes may alter the efficacy of hormonal contraception. The continuous use
of hormonal contraception by a female subject should be combined with the use of a condom by the male partner.
9. Male subjects must practice true abstinence or agree to use a condom during sexual contact with their sexual partner, pregnant female or a female of childbearing potential while participating in the study, and for at least 1 month (sufficiently exceeding 5 times the mean t1/2 of VIT-2763 based on multiple dose human PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of s

Exclusion Criteria

1. Documented diagnosis of Hb S/ß-thalassaemia, a-thalassaemia (e.g., Hb H disease), or delta beta (dß)-thalassaemia, or hereditary persistence of foetal Hb.
2. Known previous or concomitant serious illness, medical condition or physical condition that may be associated with increased risk to the subject, or may interfere with study assessments, outcomes, or the ability to provide written informed consent or comply with study procedures, in the Investigator’s opinion.
Note: A subject tested positive using nucleic acid amplification testing, antigen, or antibody detection for SARS-CoV-2 test within 2 weeks preceding screening or during screening, will be excluded but can be rescreened once at a later time point as per Investigator’s judgment and if confirmation of a negative SARS-CoV-2 test is available based on standard of care.
3. Subjects with history of partial or total splenectomy within 4 months prior to screening.
4. History of myocardial iron overload as defined by a cardiac T2* <20 ms by MRI, and/or a documented LIC >15 mg/g liver dry weight assessed through MRI.
Note: Results from existing T2* or LIC MRI results will be taken into account for eligibility assessment in case the examinations were performed within 12 months prior to screening. In those cases, where cardiac T2* MRI results or LIC MRI results are not available from the subject's history, the results from the cardiac T2* and LIC MRI will be assessed during screening.
5. Chronic liver disease or history of liver cirrhosis, and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST), above 3-fold the upper limit of normal (ULN) range at screening.
6. Clinically relevant renal disease, including estimated glomerular filtration rate (eGFR) =45 ml/min/1.73 m2 (according to chronic kidney disease classification Stage 4 or higher), and/or significant urinary albumin/creatinine ratio >3 mg/mmol at screening.
Note: eGFR should be estimated according to Chronic Kidney Disease Epidemiology Collaboration formula (CKI-EPI).
7. Any history or clinically important finding of cardiac disorders, such as clinically relevant cardiac arrhythmia, cardiac insufficiency, cardiomyopathy, coronary disease, family history of congenital long QT syndrome, family history of sudden death, valve disorder, or heart failure according to New York Heart Association (NYHA) Classification 3-4.
8. Clinically relevant abnormal 12-lead ECG findings during screening or prior to randomisation (as deemed by the Investigator), including (but not limited to) second, or third degree atrioventricular block or QTcF >450 msec.
9. Any history of clinically significant lung disease, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, or pulmonary hypertension Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
10. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy at the time of screening. Note: A subject meeting this criterion should delay screening and/or enrolment until 2 weeks post-therapy, or would be excluded but can be rescreened at maximum 2 times at a later time point.
11. [...]

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified