Clinical Study of CN128 in Thalassemia Patients

NCT03673085 | Completed Phase 1

• 1 other identifier: D160605
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

• To determine the maximum tolerated dose (MTD) of CN128 for single oral administration in thalassemia patients aged 16 and above
• To study the pharmacokinetics of CN128 in thalassemia patients aged 16 and above
• Design:
• Subject inclusion criteria:
• Thalassemia patients with serum ferritin ≥500 μg/L
• Patients aged 16 and above
• Without blood transfusion within 1 week before admission, with hemoglobin ≥ 80 g/L
• Voluntarily participate in the experiment, and the process of obtaining informed consent form meeting the requirements of GCP
• Subject exclusion criteria:
• Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive
• Patients with history of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic multiple intestinal polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other patients whom investigators believe to have potential intestinal complications
• Liver dysfunction (ALT or AST \> 2.5×ULN); or renal dysfunction (serum creatinine \> 1.5×ULN)
• Uncontrolled active infections
• Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs
• ect.
• Usage:
• Pharmacokinetic assessment of CN128 administration:
• Safety and tolerability assessments:
• Statistics

Conditions

Thalassemia

Outcome Measures

Primary Outcomes (21)

• Change from baseline in Temperature

  Vital signs checks

  Day 1 to Day 8

• Change from baseline in Pulse

  Vital signs checks; determine the patient's pulse which is one kind of physiological parameter

  Day 1 to Day 8

• Change from baseline in Respiration

  Vital signs checks; determine the patient's respiration which is one kind of physiological parameter

  Day 1 to Day 8

• Change from baseline in Blood pressure

  Vital signs checks; both systolic and diastolic will be measured

  Day 1 to Day 8

• Skin examination

  Physical examination

  Day 1 to Day 8

• Change from baseline in Height

  Physical examination

  Day 1 to Day 8

• Change from baseline in Weight

  Physical examination

  Day 1 to Day 8

• Blood examination

  Laboratory test: WBC, RBC, NEUT, BASO, etc.

  Day 1 to Day 8

• Urine examination

  Laboratory test: colour, appearance, glucose, protein, ketone, bilirubin, leukocyte, blood, and microscopic

  Day 1 to Day 8

• Blood biochemical examination

  Laboratory test: ALT, AST, ALP, LDH, AMS, BUN, ALB, etc.

  Day 1 to Day 8

• Change from baseline in Serum iron

  Laboratory test: Serum iron

  Day 1 to Day 8

• Blood coagulation function

  Laboratory test: fibrinogen, prothrombin time and corresponding INR, APTT

  Day 1 to Day 8

• Electrocardiogram

  Laboratory test: heart rate and QTc

  Day 1 to Day 8

• Number of subjects with adverse events

  Adverse events

  Day 1 to Day 8

• AUC0-t of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• AUC0-∞ of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• Cmax of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• t1/2 of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• CL/F of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• Vd/F of CN128

  Pharmacokinetics parameters

  0h to 48h after study drug administration

• MRT of CN128

  Pharmacokinetics parameters: mean residence time

  0h to 48h after study drug administration

Study Arms (16)

Group 1-1

EXPERIMENTAL

The dose of CN128 is 2.5 mg/kg bw.

Drug: CN128

Group 1-2

PLACEBO COMPARATOR

The dose of placebo is 2.5 mg/kg bw.

Other: placebo

Group 2-1

EXPERIMENTAL

The dose of CN128 is 5 mg/kg bw.

Drug: CN128

Group 2-2

PLACEBO COMPARATOR

The dose of placebo is 5 mg/kg bw.

Other: placebo

Group 3-1

EXPERIMENTAL

The dose of CN128 is 10 mg/kg bw.

Drug: CN128

Group 3-2

PLACEBO COMPARATOR

The dose of placebo is 10 mg/kg bw.

Other: placebo

Group 4-1

EXPERIMENTAL

The dose of CN128 is 15 mg/kg bw.

Drug: CN128

Group 4-2

PLACEBO COMPARATOR

The dose of placebo is 15 mg/kg bw.

Other: placebo

Group 5-1

EXPERIMENTAL

The dose of CN128 is 20 mg/kg bw.

Drug: CN128

Group 5-2

PLACEBO COMPARATOR

The dose of placebo is 20 mg/kg bw.

Other: placebo

Group 6-1

EXPERIMENTAL

The dose of CN128 is 30 mg/kg bw.

Drug: CN128

Group 6-2

PLACEBO COMPARATOR

The dose of placebo is 30 mg/kg bw.

Other: placebo

Group 7-1

EXPERIMENTAL

The dose of CN128 is 45 mg/kg bw.

Drug: CN128

Group 7-2

PLACEBO COMPARATOR

The dose of placebo is 45 mg/kg bw.

Other: placebo

Group 8-1

EXPERIMENTAL

The dose of CN128 is 60 mg/kg bw.

Drug: CN128

Group 8-2

PLACEBO COMPARATOR

The dose of placebo is 60 mg/kg bw.

Other: placebo

Interventions

CN128 DRUG

CN128

Group 1-1; Group 2-1; Group 3-1; Group 4-1; Group 5-1; Group 6-1; Group 7-1; Group 8-1

placebo OTHER

The tablets without CN128

Group 1-2; Group 2-2; Group 3-2; Group 4-2; Group 5-2; Group 6-2; Group 7-2; Group 8-2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Thalassemia patients with serum ferritin ≥500 μg/L
• Patients aged 16 and above
• Without blood transfusion within 1 week before admission, with hemoglobin ≥ 80 g/L
• Voluntarily participate in the experiment, and the process of obtaining informed consent form meeting the requirements of GCP

You may not qualify if:

• Hepatitis B surface antigen positive, hepatitis B core antibody positive and HBV-DNA positive, hepatitis C anti-HCV positive, HIV positive, Treponema pallidum positive
• Patients with history of active digestive tract diseases (including gastric ulcer, duodenal ulcer, gastroesophageal varices, ulcerative colitis, Crohn's disease, digestive tract tumors, familial genetic multiple intestinal polyps), history of digestive tract perforation, history of digestive tract surgery and influence on drug absorption, and other patients whom investigators believe to have potential intestinal complications
• Liver dysfunction (ALT or AST \> 2.5×ULN); or renal dysfunction (serum creatinine \> 1.5×ULN)
• Uncontrolled active infections
• Patients currently taking CYP3A strong inducer or inhibitor drugs or drugs that may prolong the QT interval without temporary suspension of use or temporary substitution of the said drugs
• Allergic constitution: allergic to or with contraindication of main ingredients or excipients of CN128 tablets (microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, silica, sodium stearate fumarate, Opadry)
• Patients who have abnormal ECG with clinical significance: congenital long QT syndrome or known family history of long QT syndrome; QTc \> 450ms (male) or QTc \> 470ms (female); patients who have ventricular or atrial tachyarrhythmia with clinical significance, etc.
• Family planning participants (including male subjects) during or within three months after the trial
• Patients with a history of blood donation within 3 months before the trial
• Patients with a history of smoking (more than 5 cigarettes or products with equivalent nicotine per day), alcoholism (more than 14 units of alcohol per week: 1 alcohol unit equals 10 mL or 8 g pure alcohol; 25 mL 40% liquor, 330 mL 5% beer, 175 mL 12% red wine equals 1.0, 1.5, 2.0 alcohol units respectively), drug abuse and addiction history
• Patients who smoke, drink or eat any food containing alcohol, xanthine or grapefruit (including chocolate, tea, coffee or cola drinks) within 48 h before the using of test drug
• The subject of any other clinical trials within 3 months before using of the test drug except for non interventional studies
• Patients with positive results of nicotine and urine drug screening
• Patients with difficult venous blood collection
• Any patient with conditions which the investigators resume inappropriate to participate in this study, such as: poor health status, poor compliance, unwillingness or inability to comply with treatment regimens, including delayed visits

Sponsors & Collaborators

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

Study Sites (1)

The first affiliated hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Thalassemia

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

Study Officials

• Jianzhong Shentu

  Single center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: September 17, 2018
• Study Start: January 5, 2018
• Primary Completion: October 16, 2018
• Study Completion: December 17, 2019
• Last Updated: December 19, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)