Clinical trial NCT05355766: Long-term Clinical Study of CN128 in Thalassemia With Sever Liver Iron Overloaded Patients
Official title: Phase IIb Clinical Study to Assess the Safety and Efficacy of CN128 Tablets in the Treatment of Iron Overload in Transfusion Dependent Thalassemia With Sever Liver Iron Overloaded Patients Aged 16 and Above
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thalassemia
Iron Overload
Lead sponsor: Hangzhou Zede Pharma-Tech Co., Ltd.
Sponsor class: OTHER
First posted: 2022-05-02
Enrollment: 16
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The safety and efficacy of CN128 is studied in thalassaemia with sever liver iron overloaded patients.

Detailed description: 1. The study is designed as a single arm and opened phase IIb clinical trial, so as to investigate the safety and efficacy of CN128.
2. A total of 50 eligible subjects are planned to be enrolled, and orally administration of CN128 for 52 weeks according to the administration plan.
3. Administration plan:

The trial will start with the lower dose of CN128 (10 mg/kg body weight \[bw\], bid) for one week. If no unacceptable toxicity associated with CN128 is found, the subjects will be given 15 mg/kg body weight \[bw\], bid for one week. If no unacceptable toxicity associated with CN128 is found, the subjects will be given 20 mg/kg body weight \[bw\], bid for two weeks. If no unacceptable toxicity associated with CN128 is found, the subjects will be given 25 mg/kg body weight \[bw\], bid for two weeks. If no unacceptable toxicity associated with CN128 is found, the subjects will be given 30 mg/kg body weight \[bw\], bid for two weeks. If no unacceptable toxicity associated with CN128 is found, the subjects will be given 30 mg/kg body weight \[bw\], bid to Week 52. Dosage will be adjusted according to subject status and study plan.

Eligibility 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.
* Severe iron overloaded patients (serum ferritin\>2500 µg/L or liver iron concentration (LIC)\>15 mg/g dw) despite prior treatment with at least one iron chelator.
* 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 Alkaline Phosphatase (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 Aminotransferase (AST) \> 2.5 × upper limit of normal (ULN), or serum creatinine \> 1.5 × ULN.
* Neutropenia patient (neutrophil count \< 1.5 × 10\^9 / L).
* Active infection uncontrolled.
* Autoimmune hemolytic anemia patients.
* 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.
* Cardiac iron overloaded patients, cardiac magnetic resonance MRI T2\*\<10 ms
* 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 interval\>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 four weeks before taking the test preparation, except for non-interventional studies.
* Pregnant or lactating women.
* Unsuitable to participate in the trial considered by the researchers.

Primary outcomes:
measure: 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.
timeFrame: Up to 52 weeks
measure: Absolute Change in Weight (Unit: kg) From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
measure: Absolute Change in Height (Unit: m) From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
measure: Absolute Change in Temperature (Unit: ℃）From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
measure: Absolute Change in Blood pressure (Unit: mmHg ) From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
measure: Absolute Change in Heart rate (Unit: bpm) From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
measure: Absolute Change in Respiration (Unit: bpm) From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
measure: Absolute Change in Electrocardiogram (P-R (Unit: ms), QRS (Unit: ms), QTc interval (Unit: ms), etc) From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
measure: Change in Auditory Function From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in White Blood Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Neutrophil Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Lymphocyte Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Monocyte Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Eosinophilic Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Basophilic Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Red Blood Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Hemoglobin (Unit: g/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Hematocrit (Unit:%) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Blood Platelet Count (Unit: 10^9/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Thrombocytocrit (Unit: %) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Alanine Aminotransferase (Unit: U/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Total Bilirubin (Unit:µmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Total Protein (Unit:g/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Albumin (Unit: g/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Globulin (Unit: g/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Alkaline Phosphatase (Unit: U/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Aspartate Aminotransferase (Unit: U/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Lactate Dehydrogenase (Unit: IU/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Urea (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Creatinine (Unit:µmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Glucose (Unit: mmol/L) From Baseline Over Time [ Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Potassium (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Sodium (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Chlorine (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Calcium (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Fibrinogen (Unit: g/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Prothrombin time (Unit: s) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Activated Partial Thromboplastin Time (APTT, Unit: s) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Serum Total Thyroxine (Unit: nmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Parathyroid Hormone (Unit: pg/mL) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Total Triiodothyronine (Unit: nmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Thyrotropin (Unit: mIU/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Urine Glucose (Unit: mmol/L) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Urine Protein (Unit: g/L)) From Baseline Over Time
timeFrame: Baseline, 2, 12, 26, 39 and 52 weeks.
measure: Absolute Change in Total Testosterone (Unit: ng/ml) in men From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
measure: Absolute Change in Free Testosterone (Unit: nmol/L) in men From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
measure: Absolute Change in Follicle-generating Hormone (Unit: mIU/mL) in women From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
measure: Absolute Change in Luteinizing Hormon (Unit: mIU/mL) in women From Baseline Over Time
timeFrame: Baseline, 26, 39 and 52 weeks.
Secondary outcomes:
measure: Absolute Change in Liver iron content (Unit: mg/g dw) From Baseline Over Time
timeFrame: Baseline, 12, 26,39 and 52 weeks.
measure: Absolute Change in Serum ferritin (Unit: µg/L) From Baseline Over Time
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, 26, 39 and 52 weeks.
Other outcomes:
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital Of Guangxi Medical University
state: Guangxi
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: Jianmin Luo, PhD
role: PRINCIPAL_INVESTIGATOR
References: