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

NCT04059406 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: ISIS 702843-CS22019-003505-96
• Study Type: interventional
• Target: 29
• Locations: 5 countries
• Sites: 19

Brief 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.

Conditions

Beta Thalassemia Intermedia

Keywords

Thalassaemia; Beta Thalassemia; IONIS TMPRSS6-LRx

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53

  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

  Week 53

Study Arms (3)

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.

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

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.

Drug: sapablursen

Interventions

sapablursen DRUG

sapablursen administered subcutaneously

Also known as: ISIS 702843, IONIS TMPRSS6-LRx

Cohort A: Sapablursen; Cohort B: Sapablursen; Cohort C: Sapablursen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (19)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Aghia Sophia General Children's Hospital

Athens, Attica, 115 27, Greece

Location

University General Hospital of Patras

Patra, Peloponnese, 26 504, Greece

Location

Koutlimbaneio & Triantafylleio General Hospital of Larissa

Larissa, Thessaly, 412 21, Greece

Location

Chronic Care Center

Hazmiyeh, Lebanon

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Thammasat University Hospital

Pathum Thani, 12120, Thailand

Location

King Chulalongkorn Memorial Hospital

Pathum Wan, 10330, Thailand

Location

Naresuan University Hospital

Phitsanulok, 65000, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Cukurova Üniversitesi Tıp Fakültesi

Adana, 1330, Turkey (Türkiye)

Location

Hacettepe Üniversitesi Tıp Fakültesi

Ankara, 6100, Turkey (Türkiye)

Location

Akdeniz University Faculty of Medicine

Antalya, 07070, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35100, Turkey (Türkiye)

Location

İstanbul Üniversitesi - Istanbul Tıp Fakültesi

Topkapı, 34093, Turkey (Türkiye)

Location

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

globalregulatoryaffairs@ionis.com

760-603-2346

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 16, 2019
• Study Start: September 24, 2020
• Primary Completion: March 28, 2023
• Study Completion: March 28, 2023
• Last Updated: February 18, 2025
• Results First Posted: February 18, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GR (3); TH (7); AU (3); LE (1); TU (5)