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

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 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 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, 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 * 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