A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Patients with Non-Transfusion Dependent ß-Thalassemia Intermedia
- Conditions
- Chronic anemia due to ineffective erythropoiesis (IE) in subjects with ß thalassemiathalassemia
- Registration Number
- LBCTR2020071296
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 36
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.
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 < LLN, or 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) < 45 mL/min/1.73 m2, using CKD-EPI
10. Clinically significant liver function test (LFT) abnormalities
11. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)> 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ame: HB = 1.0 g/dL;Timepoints: Week 27 of treatment;Measure: Hemoglobin test
- Secondary Outcome Measures
Name Time Method ame: 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