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

Beta Thalassemia Intermedia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04059406
• Other study ID #: ISIS 702843-CS2
• Secondary ID: 2019-003505-96
• Status: Terminated
• Phase: Phase 2
• Start date: September 24, 2020
• Est. completion date: March 28, 2023

Study information

• Verified date: February 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

• a-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

Related Conditions & MeSH terms

• Beta Thalassemia Intermedia
• beta-Thalassemia
• Thalassemia

Intervention

Drug:
• sapablursen
sapablursen administered subcutaneously

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Greece	Aghia Sophia General Children's Hospital	Athens	Attica
Greece	Koutlimbaneio & Triantafylleio General Hospital of Larissa	Larissa	Thessaly
Greece	University General Hospital of Patras	Patra	Peloponnese
Lebanon	Chronic Care Center	Hazmiyeh
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai
Thailand	Srinagarind Hospital	Khon Kaen
Thailand	Thammasat University Hospital	Pathum Thani
Thailand	King Chulalongkorn Memorial Hospital	Pathum Wan
Thailand	Naresuan University Hospital	Phitsanulok
Thailand	Songklanagarind Hospital	Songkhla
Turkey	Cukurova Üniversitesi Tip Fakültesi	Adana
Turkey	Hacettepe Üniversitesi Tip Fakültesi	Ankara
Turkey	Akdeniz University Faculty of Medicine	Antalya
Turkey	Ege Universitesi Tip Fakultesi	Izmir
Turkey	Istanbul Üniversitesi - Istanbul Tip Fakültesi	Topkapi

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Australia,  Greece,  Lebanon,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with a = 1.0 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 27		Baseline and Week 27
Secondary	Percentage of participants with a = 1.5 grams per deciliter (g/dL) increase from Baseline in hemoglobin (Hb) at Week 53		Baseline and Week 53
Secondary	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		Baseline and Week 53