Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx)

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.

Study Overview

• Status: Terminated
• Conditions: Beta Thalassemia Intermedia
• Intervention / Treatment: Drug: sapablursen

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Greece
  • Attica
    • Athens, Attica, Greece, 115 27
      • Aghia Sophia General Children's Hospital
  • Peloponnese
    • Patra, Peloponnese, Greece, 26 504
      • University General Hospital of Patras
  • Thessaly
    • Larissa, Thessaly, Greece, 412 21
      • Koutlimbaneio & Triantafylleio General Hospital of Larissa
• Lebanon
  • Hazmiyeh, Lebanon
    • Chronic Care Center
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Pathum Thani, Thailand, 12120
    • Thammasat University Hospital
  • Pathum Wan, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Phitsanulok, Thailand, 65000
    • Naresuan University Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind hospital
• Turkey
  • Adana, Turkey, 1330
    • Cukurova Üniversitesi Tıp Fakültesi
  • Ankara, Turkey, 6100
    • Hacettepe Üniversitesi Tıp Fakültesi
  • Antalya, Turkey, 07070
    • Akdeniz University Faculty of Medicine
  • Topkapı, Turkey, 34093
    • İstanbul Üniversitesi - Istanbul Tıp Fakültesi
  • İzmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi

Participation Criteria

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 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

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, 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Sapablursen; 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.	Drug: sapablursen; sapablursen administered subcutaneously; Other Names: ISIS 702843; IONIS TMPRSS6-LRx
Experimental: Cohort B: Sapablursen; 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	Drug: sapablursen; sapablursen administered subcutaneously; Other Names: ISIS 702843; IONIS TMPRSS6-LRx
Experimental: Cohort C: Sapablursen; 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.	Drug: sapablursen; sapablursen administered subcutaneously; Other Names: ISIS 702843; IONIS TMPRSS6-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27	Blood hemoglobin	Baseline and Week 27

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53	Blood hemoglobin	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	Week 53

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

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 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Thalassaemia; Beta Thalassemia; IONIS TMPRSS6-LRx
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• 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