Long-term Clinical Study of CN128 in Thalassemia Patients

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

1. Primary objectives:

• To evaluate the safety and efficacy of long-term orally administration of CN128 in thalassaemia patients with blood transfusion dependent and aged 16 and above.

2. Design:

• 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 48 weeks.

• Subjects' medication status, uncomfortable symptoms, concomitant medication or non-drug therapy were recorded daily.

3. 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.

4. 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;

• etc.

5. 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.

6. Safety assessments:

Safety evaluations include adverse events, adverse reactions, severe adverse events, and severe adverse reactions; growth; total and free testosterone in men, follicle-generating hormone and luteinizing hormonin in women; vital signs and electrocardiogram; hearing, laboratory test, urine pregnancy test (women of childbearing age), etc.

7. Efficacy assessments:

Efficacy evaluations include serum ferritin, liver iron content (MRI R2) and cardiac iron content (MRI T2*).

8. 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.

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

Details

• Lead Sponsor: Hangzhou Zede Pharma-Tech Co., Ltd.

Criteria

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.

Exclusion Criteria:

• 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.