Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS TMPRSS6-LRx

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose is to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of IONIS TMPRSS6-LRx administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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