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

Primary Purpose

Beta Thalassemia Intermedia

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
sapablursen
Sponsored by
Ionis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Beta Thalassemia Intermedia focused on measuring Thalassaemia, Beta Thalassemia, IONIS TMPRSS6-LRx

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Royal Prince Alfred Hospital
  • Monash Medical Centre
  • Royal Perth Hospital
  • Aghia Sophia General Children's Hospital
  • University General Hospital of Patras
  • Koutlimbaneio & Triantafylleio General Hospital of Larissa
  • Chronic Care Center
  • Siriraj Hospital
  • Maharaj Nakorn Chiang Mai Hospital
  • Srinagarind Hospital
  • Thammasat University Hospital
  • King Chulalongkorn Memorial Hospital
  • Naresuan University Hospital
  • Songklanagarind Hospital
  • Cukurova Üniversitesi Tıp Fakültesi
  • Hacettepe Üniversitesi Tıp Fakültesi
  • Akdeniz University Faculty of Medicine
  • Ege Universitesi Tip Fakultesi
  • İstanbul Üniversitesi - Istanbul Tıp Fakültesi

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sapablursen

Arm Description

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

Outcomes

Primary Outcome Measures

Percentage of participants with a ≥ 1.0 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 27

Secondary Outcome Measures

Percentage of participants with a ≥ 1.5 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at 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

Full Information

First Posted
August 14, 2019
Last Updated
April 28, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04059406
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why 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.
Study Start Date
September 24, 2020 (Actual)
Primary Completion Date
March 28, 2023 (Actual)
Study Completion Date
March 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta Thalassemia Intermedia
Keywords
Thalassaemia, Beta Thalassemia, IONIS TMPRSS6-LRx

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sapablursen
Arm Type
Experimental
Arm Description
A single injection of sapablursen at multiple dose levels, administered subcutaneously every 4 weeks
Intervention Type
Drug
Intervention Name(s)
sapablursen
Other Intervention Name(s)
ISIS 702843, IONIS TMPRSS6-LRx
Intervention Description
sapablursen administered subcutaneously
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
Aghia Sophia General Children's Hospital
City
Athens
State/Province
Attica
ZIP/Postal Code
115 27
Country
Greece
Facility Name
University General Hospital of Patras
City
Patra
State/Province
Peloponnese
ZIP/Postal Code
26 504
Country
Greece
Facility Name
Koutlimbaneio & Triantafylleio General Hospital of Larissa
City
Larissa
State/Province
Thessaly
ZIP/Postal Code
412 21
Country
Greece
Facility Name
Chronic Care Center
City
Hazmiyeh
Country
Lebanon
Facility Name
Siriraj Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Maharaj Nakorn Chiang Mai Hospital
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Srinagarind Hospital
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Thammasat University Hospital
City
Pathum Thani
ZIP/Postal Code
12120
Country
Thailand
Facility Name
King Chulalongkorn Memorial Hospital
City
Pathum Wan
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Naresuan University Hospital
City
Phitsanulok
ZIP/Postal Code
65000
Country
Thailand
Facility Name
Songklanagarind Hospital
City
Songkhla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Cukurova Üniversitesi Tıp Fakültesi
City
Adana
ZIP/Postal Code
1330
Country
Turkey
Facility Name
Hacettepe Üniversitesi Tıp Fakültesi
City
Ankara
ZIP/Postal Code
6100
Country
Turkey
Facility Name
Akdeniz University Faculty of Medicine
City
Antalya
ZIP/Postal Code
07070
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi
City
İzmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
İstanbul Üniversitesi - Istanbul Tıp Fakültesi
City
Topkapı
ZIP/Postal Code
34093
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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