Chronic anemia due to ineffective erythropoiesis (IE) in subjects with ß thalassemia thalassemia
Conditions
Interventions
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Patient must have given written informed consent and be able to comply with all study requirements 2. Aged 18-65 years old, inclusive, at the time of informed consent 3. Clinical diagnosis of ß-Thalassemia Intermedia with genotypic confirmation of ß-globin gene mutations including but not limited to Hemoglobin E (HbE)/ß-thalassemia 4. Patient must be non-transfusion dependent as defined by: No more than 6 transfusions in the past 12-month period, and no transfusions in the 8-week period prior to Day 1 5. Mean Hb within the range 6.0-10.0 g/dL, inclusive, with this mean based on all Hb measurements taken in the Screening Period that are at least 6 weeks after the most recent transfusion for that patient. This mean must be based on at least 2 Hb measurements 6. LIC within the range of 3.0-20.0 mg Fe/g dry weight, inclusive 7. Chelators will be permitted provided the patient has been on a stable dose for at least 3 months prior to Day 1, with LIC > 5.0 mg Fe/g dry weight and serum ferritin > 300 ng/mL 8.Females must be non-pregnant and non-lactating, and one of the following: (i) surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), (ii) postmenopausal (defined as 12 months of spontaneous amenorrhea without an alternative medical cause and follicle stimulating hormone [FSH] levels in the postmenopausal range for the laboratory involved), (iii) abstinent, or (iv) if engaged in sexual relations of child-bearing potential, the patient must be using a highly effective contraceptive method from the time of signing the informed consent form until at least 13 weeks after the last dose of ISIS 702843 Males must be one of the following: (i) surgically sterile, (ii) abstinent, or (iii) if engaged in sexual relations with a female of child-bearing potential, the patient must be using a highly effective contraceptive method from the time of signing the informed consent form until at least 13 weeks after the last dose of ISIS 702843.
Exclusion criteria
Exclusion criteria: 1. Genotypic confirmation of either a-globin gene triplication or sickle hemoglobin (HbS)/ß-thalassemia, as determined by genetic assessment of blood-related disorders 2. Clinically significant abnormalities in medical history or physical examination, which at the discretion of the PI will pose significant additional risk to the patient in participating in the study 3. Clinically significant abnormalities in Screening laboratory values that would render a patient unsuitable for inclusion, at the discretion of the PI 4. Current use of iron-chelation therapy if LIC is 3.0–5.0 mg Fe/g dry weight, inclusive, or if serum ferritin = 300 ng/mL 5. Symptomatic splenomegaly, including abdominal pain or organ obstruction, or evidence of hypersplenism, such as low white blood cell (WBC) count and/or low platelets 6. Platelet count 1,000 x 109/L 7. Significant concurrent/recent coagulopathy; history of non-traumatic significant bleeding; history of immune thrombocytopenic purpura (ITP); current use of SC anti-coagulants; history of thrombotic events, including stroke or deep vein thrombosis (DVT) 8. Clinically significant renal dysfunction which at the discretion of the PI will pose significant additional risk to the patient in participating in the study 9. Estimated glomerular filtration rate (eGFR) 3.0 × ULN 12. Historical diagnosis of cirrhosis, or current signs and symptoms of cirrhosis 13. Fasting blood glucose > 2.0 × ULN 14. Significant pulmonary hypertension (PHT) defined as tricuspid regurgitation > 3.0 meters per second (m/s) on echocardiography and/or requiring treatment 15. Uncontrolled hypertension (which for this protocol is considered > 140 mm Hg systolic or > 90 mm Hg diastolic) 16. Heart failure class 3 or higher (New York Heart Association, NYHA) 17. Ejection fraction < 50% by echocardiogram, multigated acquisition (MUGA), or cardiac magnetic resonance imaging (MRI) 18. Patients unable to have MRI performed, for example, because of a pacemaker or implantable cardioverter-defibrillator (MRI is being used to measure LIC) 19. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Day 1 20. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C (unless treatment has caused the patient to test negative for hepatitis C), or chronic hepatitis B 21. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator 22. Recent introduction of hydroxyurea (within 6 months prior to Day 1) 23. Treatment with or exposure to another investigational drug, biological agent, ASO, small interfering ribonucleic acid (siRNA), or device within one month of Screening, or 5 half-lives of investigational agent, whichever is longer; or: -Treatment with or exposure to sotatercept (ACE-011), luspatercept (ACE-536), or ruxolitinib within 4 months of Screening -Treatment with or exposure to hematopoietic stimulating agents (e.g., EPOs) or any hypoxia-inducible factor prolyl hydroxylase inhibitors -Prior bone marrow transplant, stem cell transplant, or gene therapy 24. Regular use of alcohol w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: HB = 1.0 g/dL;Timepoints: Week 27 of treatment;Measure: Hemoglobin test | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: HB = 1.5 g/dL increase from Baseline;Timepoints: Week 53 of treatment;Measure: Hemoglobin test;Name: LIC = 1.0 mg Fe/g dry weight decrease from Baseline;Timepoints: Week 53 of treatment;Measure: LIC measured by MRI | — |
Countries
Australia, Canada, Greece, Lebanon, Thailand, Turkey
Contacts
Public ContactAziz Zoghbi
Regional Manager
Outcome results
None listed