Beta Thalassemia IntermediaPhase 2NCT04059406
Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx)
A Phase 2 study testing sapablursen in people with Beta Thalassemia Intermedia, run by Ionis Pharmaceuticals, Inc. at 19 sites in 5 countries.
Trial summary
The purpose was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Beta Thalassemia Intermedia
- What is being tested?
- sapablursen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 19 sitesin 5 countries
- Study dates
- 24 Sep 2020to 28 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 liver iron concentration (LIC) > 5.0 mg iron (Fe) per gram of dry weight of liver (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
Who cannot join
- 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
Show all 18Show fewer
- 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, antisense oligonucleotide (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
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
Thailand7 sites
Siriraj Hospital
Bangkok, 10700
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
Srinagarind Hospital
Khon Kaen, 40002
Thammasat University Hospital
Pathum Thani, 12120
King Chulalongkorn Memorial Hospital
Pathum Wan, 10330
Naresuan University Hospital
Phitsanulok, 65000
Songklanagarind Hospital
Songkhla, 90110
Turkey (Türkiye)5 sites
Cukurova Üniversitesi Tıp Fakültesi
Adana, 1330
Hacettepe Üniversitesi Tıp Fakültesi
Ankara, 6100
Akdeniz University Faculty of Medicine
Antalya, 07070
Ege Universitesi Tip Fakultesi
Izmir, 35100
İstanbul Üniversitesi - Istanbul Tıp Fakültesi
Topkapı, 34093
Australia3 sites
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
Royal Perth Hospital
Perth, Western Australia, 6000
Greece3 sites
Aghia Sophia General Children's Hospital
Athens, Attica, 115 27
Koutlimbaneio & Triantafylleio General Hospital of Larissa
Larissa, Thessaly, 412 21
University General Hospital of Patras
Patra, Peloponnese, 26 504
About this study
Official title: 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 was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.
Read the detailed description
This was a multi-center, randomized, open-label study in up to 29 participants. The duration of participation for each subject in the study was approximately 29 months and included an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.
- Conditions
- Beta Thalassemia Intermedia
- Being tested
- sapablursen
- Keywords
- Thalassaemia, Beta Thalassemia, IONIS TMPRSS6-LRx
- Medical subject headings
- beta-Thalassemia, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sapablursenDrug
Also called ISIS 702843, IONIS TMPRSS6-LRx
sapablursen administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Sapablursen | Experimental | Subjects initially received 30 mg/0.3 mL of sapablursen by (subcutaneous) SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks. Receives: Drug: sapablursen |
| Cohort B: Sapablursen | Experimental | Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks Receives: Drug: sapablursen |
| Cohort C: Sapablursen | Experimental | Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks. Receives: Drug: sapablursen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27
Blood hemoglobin
Measured: Baseline and Week 27
Secondary outcomes (2)
Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53
Blood hemoglobin
Measured: Week 53
Percentage of Participants With a ≥1.0 Milligrams of Iron Per Grams of Dry Weight of Liver (mg Fe/g) Decrease From Baseline in Liver Iron Concentration (LIC) at Week 53
Liver iron content
Measured: Week 53
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2019
- Study start24 Sep 2020
- Primary completion28 Mar 2023
- Study completion28 Mar 2023
Why it stopped: Favorable safety and tolerability were seen, but efficacy results in the mid-stage study did not meet Ionis' minimum target product profile to justify further development.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Beta Thalassemia IntermediaStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04059406
- Sponsor's protocol ID
- ISIS 702843-CS2
- Other IDs
- 2019-003505-96, 2019
- Status last verified
- Feb 2025
- First submitted
- 14 Aug 2019
- Last updated
- 18 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Taher A, Diamantidis MD, Kattamis A, Aydinok Y, Kaplan ZS, Dibble A, Dorow S, Doherty S, Mathews J, Jung S, Goldberg YP, Tami J, Bhanot S, Schneider E, Monia BP, Barrett TD. Phase 2a randomized study to evaluate sapablursen in patients with non-transfusion dependent beta-thalassemia intermedia. Blood Adv. 2026 Jun 4:bloodadvances.2026019799. doi: 10.1182/bloodadvances.2026019799. Online ahead of print.
PubMed 42241700
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04059406
- Acronym / sponsor ID
- ISIS 702843-CS2
- Conditions
- Beta Thalassemia Intermedia
- Keywords
- Thalassaemia, Beta Thalassemia, IONIS TMPRSS6-LRx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Favorable safety and tolerability were seen, but efficacy results in the mid-stage study did not meet Ionis' minimum target product profile to justify further development.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 28 Mar 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 16 Aug 2019 (actual)
- Results
- Posted 18 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.
Detailed description
This was a multi-center, randomized, open-label study in up to 29 participants. The duration of participation for each subject in the study was approximately 29 months and included an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Sapablursen | Experimental | Drug: sapablursenSubjects initially received 30 mg/0.3 mL of sapablursen by (subcutaneous) SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks. |
| Cohort B: Sapablursen | Experimental | Drug: sapablursenSubjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks |
| Cohort C: Sapablursen | Experimental | Drug: sapablursenSubjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sapablursenAlso: ISIS 702843, IONIS TMPRSS6-LRxsapablursen administered subcutaneously | Drug | Cohort A: Sapablursen, Cohort B: Sapablursen, Cohort C: Sapablursen |
Primary outcome
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
Blood hemoglobin
2 secondary outcomes
Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53
Time frame: Week 53
Percentage of Participants With a ≥1.0 Milligrams of Iron Per Grams of Dry Weight of Liver (mg Fe/g) Decrease From Baseline in Liver Iron Concentration (LIC) at Week 53
Time frame: Week 53
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42241700Taher A, Diamantidis MD, Kattamis A, Aydinok Y, Kaplan ZS, Dibble A, Dorow S, Doherty S, Mathews J, Jung S, Goldberg YP, Tami J, Bhanot S, Schneider E, Monia BP, Barrett TD. Phase 2a randomized study to evaluate sapablursen in patients with non-transfusion dependent beta-thalassemia intermedia. Blood Adv. 2026 Jun 4:bloodadvances.2026019799. doi: 10.1182/bloodadvances.2026019799. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sapablursen in people with Beta Thalassemia Intermedia, run by Ionis Pharmaceuticals, Inc. at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Thailand, Turkey (Türkiye), Australia, Greece, Lebanon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04059406, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2025.