Long-term Clinical Study of CN128 in Thalassemia Patients
Status:
Recruiting
Trial end date:
2022-06-30
Target enrollment:
Participant gender:
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.