A Study of Safety and Efficiency of AND017 in Patients With β-thalassemia

Official title

A Study of Safety and Efficiency of AND017 in Patients With Transfusion Dependent and Non-transfusion Dependent β-thalassemia

Overview

This is a phase II, randomized, double-blinded, placebo-controlled study to treat patients with transfusion-dependent and non-transfusion dependent β -thalassemia with AND017 and optimal supportive care, including blood transfusion and iron removal, based on the clinician's judgment and practice.

Interventions

• Drug AND017 capsules
  Administer AND017 capsules once per day (QD)
• Drug AND017 Placebo
  Administer AND017 matching placebo capsules once per day (QD)

Primary outcome measures

• Evaluate the safety and tolerability of different oral doses of AND017 in the treatment of β-thalassemia subjects [Time frame: From baseline to Week 24 or End of Treatment if discontinue early]

Secondary outcome measures (12)

• Change in mean Hb levels relative to baseline at weeks 8-12 and week 20-24 post-treatment compared to baseline (mean Hb values during the 4 weeks prior to the first dose). [Time frame: Baseline, Week 8-12, Week 20-24]
• The level of Hb and the change from baseline at each visit throughout the treatment period. [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Proportion of patients with mean Hb elevation ≥1.0 g/dL from baseline to weeks 8-12 after dosing. [Time frame: Baseline, Week 8-12]
• Levels of and changes from baseline in red blood cell count throughout the treatment period [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Levels of and changes from baseline in reticulocyte count throughout the treatment period [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Levels of and changes from baseline in mean corpuscular volume (MCV) throughout the treatment period [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Levels of and changes from baseline in mean corpuscular hemoglobin (MCH) throughout the treatment period [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Levels of and changes from baseline in mean corpuscular hemoglobin concentration (MCHC) throughout the treatment period [Time frame: From baseline to Week1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 18, 20, 22, 24]
• Throughout the treatment period, changes in the levels and relative baseline of transferrin will be assessed. [Time frame: From baseline to Week 4, 8, 12, 16, 20, 24]
• Throughout the treatment period, changes in the levels and relative baseline of transferrin saturation (TSAT) will be assessed. [Time frame: From baseline to Week 4, 8, 12, 16, 20, 24]
• Throughout the treatment period, changes in the levels and relative baseline of ferritin will be assessed. [Time frame: From baseline to Week 4, 8, 12, 16, 20, 24]
• Throughout the treatment period, changes in the levels and relative baseline of serum iron level will be assessed. [Time frame: From baseline to Week 4, 8, 12, 16, 20, 24]

Eligibility criteria

Inclusion criteria

• Documented diagnosis of β-thalassemia or hemoglobin E/β-thalassemia, HbS/ β-thalassemia (β-thalassemia with α-bead mutation and/or multiplication is not allowed).
• TDT subjects: receive regular blood transfusions, defined as 6-20 RBC units (including threshold) in the 24 weeks prior to screening assessment, and no transfusion-free period of ≥ 5 weeks during this period.
• NTDT cohort: having transfused <6 RBC units in the 24 weeks prior to the screening assessment, no regular transfusion schedule, and no transfusion for 4 weeks prior to the screening assessment.
• Subject transfusion records should be obtained within 24 weeks prior to the screening assessment, containing the date of transfusion, transfused RBC units, and pre-transfusion hemoglobin values.
• ECOG score 0-1.
• NTDT subjects with Hb ≤ 10.0 g/dL at screening test and one follow-up test (two tests more than one week apart) and difference in values between the two tests ≤ 1.0 g/dL.
• Adequate liver function: Total bilirubin < 1.5 x upper limit of normal (ULN) (subjects with Gilbert syndrome, i.e., unconjugated hyperbilirubinemia, have a total bilirubin < 3 x ULN), aspartate aminotransferase

Exclusion criteria

• Other causes of anemia (e.g., hemolytic anemia, history of pure red blood cell aplastic anemia, myelodysplastic syndrome, or multiple myeloma)
• Presence of active infection or inflammatory disease requiring systemic anti-infective therapy, including concomitant autoimmune diseases with inflammatory symptoms (e.g. generalized erythema, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, dry syndrome, etc.)
• Complicated retinal neovascularization requiring treatment (diabetic proliferative retinopathy, age-related exudative macular degeneration, retinal vein occlusion, macular edema, etc.)
• Inability to take oral medications, conditions with a history of gastrectomy/bowel resection that may have an effect on the absorption of gastrointestinal medications (excluding gastric polyps or colonic polypectomy), or gastroparesis that remains symptomatic on current therapy
• Clinically significant bleeding (requiring emergency blood transfusion within 12 h or a decrease in hemoglobin ≥ 2 g/dL within one week) within 4 weeks prior to the first dose, or a tendency to bleed or risk of bleeding that has not been medically or surgically corrected
• Uncontrolled hypertension, defined as a diastolic blood pressure value >95 mmHg or a systolic blood pressure >160 mmHg on 2 or more of 3 repeated blood pressure tests (each at least 5 minutes apart) during the screening period
• Complicated congestive heart failure (New York Heart Association \[NYHA\] class III or higher).
• history of stroke, transient ischemic attack (TIA), myocardial infarction, thromboembolic event (deep vein thrombosis, DVT), pulmonary embolism, or pulmonary infarction within 24 weeks prior to screening evaluation
• history of significant coagulation abnormalities, or platelet count >600 x 109/L or <80 x 109/L
• History of epilepsy or any past seizures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 5 centers

• Nanfang Hospital Southern Medical University — Guangzhou
• Maoming People's Hospital — Maoming
• Liuzhou People's Hospital — Liuzhou
• Guangxi Medical University No.1 Affiliated Hospital — Nanning
• Hainan General Hospital — Haikou

Identifiers

NCT: NCT06302491 · AND017-BTH-205

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗