- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04059406
Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx)
February 29, 2024 updated by: Ionis Pharmaceuticals, Inc.
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 β-Thalassemia Intermedia
The purpose is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.
Study Overview
Detailed Description
This is a multi-center, randomized, open-label study in up to 45 participants.
The duration of each participant in the study will be approximately 29 months and will include an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.
Study Type
Interventional
Enrollment (Actual)
29
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Camperdown, New South Wales, Australia, 2050
- Royal Prince Alfred Hospital
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Medical Centre
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Western Australia
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Perth, Western Australia, Australia, 6000
- Royal Perth Hospital
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Attica
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Athens, Attica, Greece, 115 27
- Aghia Sophia General Children's Hospital
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Peloponnese
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Patra, Peloponnese, Greece, 26 504
- University General Hospital of Patras
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Thessaly
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Larissa, Thessaly, Greece, 412 21
- Koutlimbaneio & Triantafylleio General Hospital of Larissa
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Hazmiyeh, Lebanon
- Chronic Care Center
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Bangkok, Thailand, 10700
- Siriraj Hospital
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Chiang Mai, Thailand, 50200
- Maharaj Nakorn Chiang Mai Hospital
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Khon Kaen, Thailand, 40002
- Srinagarind Hospital
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Pathum Thani, Thailand, 12120
- Thammasat University Hospital
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Pathum Wan, Thailand, 10330
- King Chulalongkorn Memorial Hospital
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Phitsanulok, Thailand, 65000
- Naresuan University Hospital
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Songkhla, Thailand, 90110
- Songklanagarind Hospital
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Adana, Turkey, 1330
- Cukurova Üniversitesi Tıp Fakültesi
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Ankara, Turkey, 6100
- Hacettepe Üniversitesi Tıp Fakültesi
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Antalya, Turkey, 07070
- Akdeniz University Faculty of Medicine
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Topkapı, Turkey, 34093
- İstanbul Üniversitesi - Istanbul Tıp Fakültesi
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İzmir, Turkey, 35100
- Ege Universitesi Tip Fakultesi
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Willingness to comply with study procedures
- Clinical diagnosis of Beta-Thalassemia Intermedia with genotypic confirmation
- 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
- Mean Hb within the range of 6.0-10.0 g/dL, inclusive at Screening
- LIC within the range of 3.0-20.0 mg Fe/g dry weight, inclusive
- If using chelators, must be on a stable dose for at least 3 months with LIC > 5.0 mg Fe/g dry weight and serum ferritin > 300 nanograms per milliliter (ng/mL)
- Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal
- Males must be surgically sterile, abstinent or using an acceptable contraceptive method
Exclusion Criteria:
- Clinically significant abnormalities in lab values, medical history, or physical examination
- α-globin gene triplication
- Symptomatic splenomegaly
- Platelet count < lower limit of normal (LLN) or > 1,000 x 10^9/L
- 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
- Clinically significant renal, liver or cardiac dysfunction
- Uncontrolled hypertension (> 140 mm Hg systolic or > 90 mm Hg diastolic)
- Fasting blood glucose > 2.0 × upper limit of normal (ULN)
- Inability to have a magnetic resonance imaging (MRI) scan
- Known history or positive test for human immunodeficiency virus (HIV), hepatitis C (HCV), or hepatitis B (HBV)
- Active infection requiring systemic antiviral or antimicrobial therapy
- Regular excessive use of alcohol
- Recent start of hydroxyurea (6 months prior to Day 1)
Treatment with or recent 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
- hematopoietic stimulating agents or any hypoxia-inducible factor prolyl hydroxylase inhibitors within 8 weeks of Day 1
- prior bone marrow transplant, stem cell transplant, or gene therapy
- Surgery associated with significant blood loss within 4 months of Screening, splenectomy within 12 months of Screening, or splenectomy scheduled during treatment
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Sapablursen Dose Level 1 (Cohort A)
A single injection of sapablursen at multiple dose levels, administered subcutaneously every 4 weeks.
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sapablursen administered subcutaneously
Other Names:
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Experimental: Sapablursen Dose Level 1 (Cohort B)
A single injection of sapablursen at multiple dose levels, administered subcutaneously every 4 weeks.
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sapablursen administered subcutaneously
Other Names:
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Experimental: Sapablursen Dose Level 1 (Cohort C)
A single injection of sapablursen at multiple dose levels, administered subcutaneously every 4 weeks.
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sapablursen administered subcutaneously
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Percentage of participants with a ≥ 1.0 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 27
Time Frame: Baseline and Week 27
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Baseline and Week 27
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Percentage of participants with a ≥ 1.5 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 53
Time Frame: Baseline and Week 53
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Baseline and Week 53
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Percentage of participants with a ≥ 1.0 milligram of iron per gram of dry weight of liver (mg Fe/g) decrease from Baseline in liver iron concentration (LIC) at Week 53
Time Frame: Baseline and Week 53
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Baseline and Week 53
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 24, 2020
Primary Completion (Actual)
March 28, 2023
Study Completion (Actual)
March 28, 2023
Study Registration Dates
First Submitted
August 14, 2019
First Submitted That Met QC Criteria
August 14, 2019
First Posted (Actual)
August 16, 2019
Study Record Updates
Last Update Posted (Actual)
March 4, 2024
Last Update Submitted That Met QC Criteria
February 29, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ISIS 702843-CS2
- 2019-003505-96 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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