A study to look at how effective, how safe and how well tolerated a study drug called ISIS 702843 is when given under the skin to patients with Non-Transfusion Dependent ß-Thalassemia Intermedia. This study will also look at the movement of ISIS 702843 in the body and how ISIS 702843 affects the body.
- Conditions
- on-Transfusion Dependentß-Thalassemia IntermediaMedDRA version: 20.0Level: LLTClassification code 10074356Term: Non-transfusion dependent thalassemiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003505-96-GR
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
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 Beta-Thalassemia Intermedia with genotypic confirmation of beta-globin gene mutations including but not limited to Hemoglobin E (HbE)/beta-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 two 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, 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.
* Abstinence is only acceptable as true abstinence, i.e., when this is in line with the
preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,
ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.
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 subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
1. Genotypic confirmation of either a-globin gene triplication or sickle hemoglobin (HbS)/beta-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 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. 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 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 (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 1 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 (HIF-PHI) (e.g., roxadustat,
vadadustat, daprodustat, molidustat, desidustat) within 8 weeks of Day 1
- Prior bone marrow transplant, stem cell transplant, or gene therapy
24. Regular use of alcohol within 6 months prior to Screening (> 7 drinks/wk for females, > 14 drinks/wk for ma
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method