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

• ClinicalTrials.gov Identifier: NCT04059406
• Recruitment Status: Terminated
• First Posted: August 16, 2019
• Last Update Posted: May 1, 2023
• Sponsor: Ionis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ionis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: August 14, 2019
• First Posted Date: August 16, 2019
• Last Update Posted Date: May 1, 2023
• Actual Study Start Date: September 24, 2020
• Actual Primary Completion Date: March 28, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 26, 2020): 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 ]
• Original Primary Outcome Measures (submitted: August 14, 2019): Percentage of participants with a ≥ 1.0 grams per deciliter (g/dL) increase from Baseline in plasma hemoglobin (Hb) at Week 27 [ Time Frame: Baseline and Week 27 ]

Current Secondary Outcome Measures (submitted: February 26, 2020)

• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: August 14, 2019)

• Percentage of participants with a ≥ 1.5 grams per deciliter (g/dL) increase from Baseline in plasma hemoglobin (Hb) at Week 53 [ Time Frame: Baseline and Week 53 ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sapablursen (Formerly ISIS 702843, IONIS-TMPRSS6-LRx)
• 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
• Brief Summary: 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Beta Thalassemia Intermedia

Intervention

Drug: sapablursen

sapablursen administered subcutaneously

Other Names:

• ISIS 702843
• IONIS TMPRSS6-LRx

Study Arms

Experimental: sapablursen

A single injection of sapablursen at multiple dose levels, administered subcutaneously every 4 weeks

Intervention: Drug: sapablursen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 28, 2023): 29
• Original Estimated Enrollment (submitted: August 14, 2019): 36
• Actual Study Completion Date: March 28, 2023
• Actual Primary Completion Date: March 28, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Greece, Lebanon, Thailand, Turkey

Administrative Information

• NCT Number: NCT04059406
• Other Study ID Numbers: ISIS 702843-CS2; 2019-003505-96 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ionis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ionis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ionis Pharmaceuticals, Inc.
• Verification Date: April 2023