Long-term Clinical Study of CN128 in Thalassemia Patients

NCT04614779 | Completed Phase 2

• 1 other identifier: A160605
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

• The study is designed as a single arm and opened phase IIa clinical trial, so as to investigate the safety and efficacy of CN128.
• A total of 50 eligible subjects are planned to be enrolled, and orally administration of CN128 for 24 weeks or 48 weeks according to the administration plan. The treatment period is from day 0 to 24 weeks, and the extended treatment period was from 25 weeks to 96 weeks.
• Subjects' medication status, uncomfortable symptoms, concomitant medication or non-drug therapy were recorded daily.
• Subject inclusion criteria:
• Thalassemia patients.
• The number of blood transfusion per month ≥1. Or hemoglobin can not be maintained at 90g/L above, if blood transfusions is less than once per month.
• Serum ferritin ≥ 500 µg/L
• Patients aged 16 and above
• Volunteer for the trial and sign the informed consent.
• Subject exclusion criteria:
• Active hepatitis B (HBsAg positive, HBsAb negative) or hepatitis C (HCV antibody positive, detectable HCV RNA, and alanine transaminase (ALT) beyond normal range)
• Active gastrointestinal disease history (including: gastric ulcer, duodenal ulcer, stomach or esophageal varices, ulcerative colitis, Crohn's disease, gastrointestinal cancer, familial genetic multiple intestinal polyps), and History of gastrointestinal perforation, gastrointestinal surgery that influence drug absorption, and other potential intestinal complications considered by researchers;
• ALT or Aspartate transaminase (AST) \> 2.5 × Upper limit of normal (ULN), or serum creatinine \> 1.5 × ULN;
• Neutropenia patient (neutrophil count \< 1.5 × 109 / L);
• Active infection uncontrolled;
• The patients who are currently taking CYP3A strong inducer or strong inhibitor drugs, or the drug that may extend the QT interval, or the drug that may decrease neutrophil count, but can not temporarily interrupt the use of such drugs;
• Congenital long QT syndrome or known family history of long QT syndrome; QTc \> 480 ms; clinically significant ventricular or atrial fast arrhythmia;
• The patients who can not accept MRI as detection means, such as claustrophobic for MRI, pacemaker, and those using ferromagnetic metal implants.
• Birth planner (including male subjects) within or within 3 months after the end of the trial;
• Participated in other clinical trials in the three months before taking the test preparation, except for non-interventional studies;
• Pregnant or lactating women;
• Unsuitable to participate in the trial considered by the researchers.
• Usage:
• All subjects will be given the lower (10 mg/kg bw, bid) or higher dose (15 mg/kg bw, bid) for 24 or 48 weeks, according to the administration plan.
• All subjects will be given the lower (15 mg/kg bw, bid) or higher dose (20 mg/kg bw, bid) for 49 or 96 weeks, according to the administration plan.
• Safety assessments:
• Efficacy assessments:
• Statistics:
• Subject characteristic distribution Demographic characteristics, general conditions, and baseline conditions (pre-treatment) of enrolled subjects were analyzed.The measurement data are described by means, standard deviation, minimum value and maximum value, while the qualitative data list frequency and percentage.
• Safety analysis Descriptive statistical analysis was used for safety endpoints.
• Effectiveness analysis Mean, standard deviation, median, minimum and maximum values were described and 95% confidence intervals were calculated. Paired T-test was used to compare each time point with the baseline if necessary. The 95% confidence interval was calculated by using Clopper-Pearson method for the proportion of patients.

Conditions

Thalassemia; Iron Overload

Outcome Measures

Primary Outcomes (48)

• Number of participants with adverse events, adverse reactions, severe adverse events and severe adverse reactions as a measure of safety and tolerability during the study period

  To determine the incidence, type and severity of adverse events, adverse reactions, severe adverse events and severe adverse reactions in patients up to 96 weeks.

  up to 96 weeks

• Absolute Change in Weight (Unit: kg) From Baseline Over Time

  The patient's weight will be determined, and it's one kind of Physical examination.

  Baseline, 24, 48, 72 and 96 weeks.

• Absolute Change in Height (Unit: m) From Baseline Over Time

  The patient's height will be determined, and it's one kind of Physical examination.

  Baseline,24, 48, 72 and 96 weeks.

• Absolute Change in Hormon (total and free testosterone in men, follicle-generating hormone and luteinizing hormon in women) From Baseline Over Time

  Hormon will be determined, and it's one kind of laboratory test.

  Baseline, 24, 48, 72 and 96 weeks.

• Absolute Change in Temperature (Unit: ℃）From Baseline Over Time

  The patient's temperature will be determined, and it's one kind of vital signs checks.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Blood pressure (Unit: mmHg ) From Baseline Over Time

  Both patient's systolic and diastolic blood pressure will be measured, and it's one kind of vital signs checks.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Heart rate (Unit: bpm) From Baseline Over Time

  The patient's heart rate will be determined, and it's one kind of vital signs checks.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Respiration (Unit: bpm) From Baseline Over Time

  The patient's respiration will be determined, and it's one kind of vital signs checks.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Electrocardiogram (P-R (Unit: ms), QRS (Unit: ms), QTc (Unit: ms), etc) From Baseline Over Time

  The patient's electrocardiogram will be measured, and it's one kind of laboratory test.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Change in Auditory Function From Baseline Over Time

  The patient's auditory function will be determined by otorhinolaryngology.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in White Blood Count (Unit: 10E9/L) From Baseline Over Time

  The patient's white blood count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Neutrophil Count (Unit: 10E9/L) From Baseline Over Time

  The patient's neutrophil count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Lymphocyte Count (Unit: 10E9/L) From Baseline Over Time

  The patient's lymphocyte count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Monocyte Count (Unit: 10E9/L) From Baseline Over Time

  The patient's monocyte count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Eosinophilic Count (Unit: 10E9/L) From Baseline Over Time

  The patient's eosinophilic count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Basophilic Count (Unit: 10E9/L) From Baseline Over Time

  The patient's basophilic count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Red Blood Count (Unit: 10E9/L) From Baseline Over Time

  The patient's red blood count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Hemoglobin (Unit: g/L) From Baseline Over Time

  The patient's hemoglobin will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Hematocrit (Unit:%) From Baseline Over Time

  The patient's hematocrit will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Blood Platelet Count (Unit: 10E9/L) From Baseline Over Time

  The patient's blood platelet count will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Thrombocytocrit (Unit: %) From Baseline Over Time

  The patient's thrombocytocrit will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Alanine Aminotransferase (Unit: U/L) From Baseline Over Time

  The patient's alanine aminotransferase will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Total Bilirubin (Unit:µmol/L) From Baseline Over Time

  The patient's total bilirubin will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Total Protein (Unit:g/L) From Baseline Over Time

  The patient's total protein will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Albumin (Unit: g/L) From Baseline Over Time

  The patient's albumin will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Globulin (Unit: g/L) From Baseline Over Time

  The patient's globulin will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Alkaline Phosphatase (Unit: U/L) From Baseline Over Time

  The patient's alkaline phosphatase will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Lactate Dehydrogenase (Unit: IU/L) From Baseline Over Time

  The patient's lactate dehydrogenase will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Urea (Unit: mmol/L) From Baseline Over Time

  The patient's urea will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Creatinine (Unit:µmol/L) From Baseline Over Time

  The patient's creatinine will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Glucose (Unit: mmol/L) From Baseline Over Time

  The patient's glucose will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Potassium (Unit: mmol/L) From Baseline Over Time

  The patient's potassium will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Sodium (Unit: mmol/L) From Baseline Over Time

  The patient's sodium will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Chlorine (Unit: mmol/L) From Baseline Over Time

  The patient's chlorine will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Calcium (Unit: mmol/L) From Baseline Over Time

  The patient's calcium will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Aspartate Aminotransferase (Unit: U/L) From Baseline Over Time

  The patient's aspartate aminotransferase will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Fibrinogen (Unit: g/L) From Baseline Over Time

  The patient's fibrinogen will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Prothrombin time (Unit: s) From Baseline Over Time

  The patient's prothrombin time will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Activated Partial Thromboplastin Time (APTT, Unit: s) From Baseline Over Time

  The patient's APTT will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Thyroid and para-gland function (Serum total thyroxine, parathyroid hormone, total triiodothyronine and thyrotropin) From Baseline Over Time

  The patient's thyroid and para-gland function will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Urine Glucose (Unit: mmol/L) From Baseline Over Time

  The patient's urine glucose will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Urine Protein (Unit: g/L)) From Baseline Over Time

  The patient's urine protein will be determined, and it's one kind of laboratory test.

  Baseline, 2, 12, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Dosage（mg/kg）during the study period

  The dosages will be investigated up to 96 weeks.

  Up to 96 weeks

• Duration of Administration during the study period

  The duration of administration will be investigated up to 96 weeks.

  Up to 96 weeks

• Number of Participants during the study period

  The number of participants will be investigated up to 96 weeks.

  Up to 96 weeks

• Absolute Change in Serum ferritin (Unit: µg/L) From Baseline Over Time

  Serum ferritin will be determined, and it's one kind of laboratory test.

  Baseline, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 weeks.

• Absolute Change in Liver iron content (MRI R2) From Baseline Over Time

  Liver iron content will be determined by liver magnetic resonance.

  Baseline, 12, 24, 48, 72 and 96 weeks.

• Absolute Change in Heart iron content (MRI T2*) From Baseline Over Time

  Heart iron content will be determined by cardio magnetic resonance.

  Baseline, 12, 24, 48, 72 and 96 weeks.

Study Arms (1)

CN128 Group

EXPERIMENTAL

All subjects will be given the lower (10 mg/kg bw, bid) or higher dose (15 mg/kg bw, bid) for 24 or 48 weeks, according to the administration plan. All subjects will be given the lower (15 mg/kg bw, bid) or higher dose (20 mg/kg bw, bid) for 49 or 96 weeks, according to the administration plan. The dosage form is tablets.

Drug: CN128 Tablets

Interventions

CN128 Tablets DRUG

Iron chelator, oral tablets

Also known as: CN128

CN128 Group

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Thalassemia patients.
• The number of blood transfusion per month ≥1. Or hemoglobin can not be maintained at 90g/L above, if blood transfusions is less than once per month.
• Serum ferritin ≥ 500 µg/L
• Patients aged 16 and above
• Volunteer for the trial and sign the informed consent.

You may not qualify if:

• Active hepatitis B (HBsAg positive, HBsAb negative) or hepatitis C (HCV antibody positive, detectable HCV RNA, and ALT beyond normal range)
• Active gastrointestinal disease history (including: gastric ulcer, duodenal ulcer, stomach or esophageal varices, ulcerative colitis, Crohn's disease, gastrointestinal cancer, familial genetic multiple intestinal polyps), and History of gastrointestinal perforation, gastrointestinal surgery that influence drug absorption, and other potential intestinal complications considered by researchers;
• ALT or AST \> 2.5 × ULN, or serum creatinine \> 1.5 × ULN;
• Neutropenia patient (neutrophil count \< 1.5 × 109 / L);
• Active infection uncontrolled;
• The patients who are currently taking CYP3A strong inducer or strong inhibitor drugs, or the drug that may extend the QT interval, or the drug that may decrease neutrophil count, but can not temporarily interrupt the use of such drugs;
• The patients who are allergic or contraindicated to the main ingredients or excipients of CN128 tablets;
• Congenital long QT syndrome or known family history of long QT syndrome; QTc \> 480 ms; clinically significant ventricular or atrial fast arrhythmia;
• The patients who can not accept MRI as detection means, such as claustrophobic for MRI, pacemaker, and those using ferromagnetic metal implants;
• Birth planner (including male subjects) within or within 3 months after the end of the trial;
• Participated in other clinical trials in the three months before taking the test preparation, except for non-interventional studies;
• Pregnant or lactating women;
• Unsuitable to participate in the trial considered by the researchers.

Sponsors & Collaborators

• Hangzhou Zede Pharma-Tech Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital Of Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

MeSH Terms

Conditions

Thalassemia; Iron Overload

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; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jianmin Jianmin, PhD

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: November 4, 2020
• Study Start: September 30, 2020
• Primary Completion: August 18, 2022
• Study Completion: August 18, 2022
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

CN (1)