Safety and Tolerance Study of Recombinant Human Albumin Injection in Healthy Subjects.

A phase I, single-center, randomized, double-blind, placebo-controlled single dose escalation study, and a positive-controlled multiple dose extension study to evaluate the safety, tolerance, pharmacokinetics and immunogenicity of recombinant human albumin injection in healthy subjects

Study Overview

• Status: Completed
• Conditions: Ascites
• Intervention / Treatment: Drug: Placebo; Drug: human albumin injection; Drug: recombinant human albumin injection

Detailed Description

This study was to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of recombinant human albumin injection in healthy volunteers. The safety, tolerance, pharmacokinetics and immunogenicity of recombinant human albumin injection were evaluated in a single center, randomized, double-blind, placebo-controlled single dose incremental trial in healthy volunteers. The study was divided into two stages: the first stage was a single dose and dose increasing stage (including 5 dose groups with increasing dose, and each group was set with placebo control); the second stage was multiple administration stage (with positive control). The safety, tolerance, pharmacokinetics, immunogenicity and other early clinical data of recombinant human albumin were collected and analyzed in the two stages. The initial dose was 1.25g. The highest dose group was set at 30g. The dose groups of 1.25, 5, 10, 20 and 30 g / time were preset in the single dose stage (dose increasing stage). The dosage was 10 g / Day in multiple administration stage.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • the First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1）Informed consent form signed; 2) To be able to complete the study; 3) Subjects (including partners) are willing to take contraceptive measures; 4) 18-55 years of age; 5) Male subjects are no less than 50 kg.Female subjects are no less than 45 kg. Body mass index is 18-28kg / m2; 6) Normal cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 50%; 7) Physical examination and vital signs are normal.

Exclusion Criteria:

1. Cigarettes Smoking subjects.
2. Allergic constitution (multiple drugs and food allergies);
3. History of drug use and/or alcohol abuse;
4. Blood donation or massive blood loss (> 450 mL) within three months before screening;
5. Taking any drugs, prescription, over-the-counter, vitamin products or herbal medicine within 14 days before screening;
6. Diet or exercise have changed recently;
7. Using study drugs within three months;
8. Risk of bleeding, such as hemorrhoids, acute gastritis or stomach and duodenal ulcers;
9. ECG abnormalities (QTc > 470ms for males, > 480ms for females);
10. Female subjects are in lactation. Pregnancy test is positive;
11. Other Clinical laboratory tests abnormalities;
12. Viral screening test is positive, including HBV, HCV, HIV, and Treponema pallidum;
13. Developing Acute disease;
14. Eating chocolate, any caffeine-containing or jaundice-rich food or drink 24 hours prior to the use of the study drug;
15. Taking any alcoholic products. Alcohol test is positive..
16. Drug test is positive. History of drug abuse or drug use in the past five years;
17. Inability for intravenous injection or blood collection;
18. Using biological products (including live vaccines) within the last 3 months. Planing to use vaccines during the study period. Having received corticosteroid or human plasma product system treatment within 1 month.
19. Renal function is abnormal, glomerular filtration rate <80 mL/min (according to the simplified MDRD formula);
20. History of glaucoma, eye disease.
21. History of cancer or other serious systemic diseases, especially heart, liver, kidney, digestive tract, nervous system, metabolic abnormalities, immune abnormalities or mental disorders;
22. History of immunodeficiency or hypofunction;
23. Received major surgery within 2 years.
24. Other subjects by investigator opinion..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control: placebo; Subjects received 0.9% sodium chloride injection.	Drug: Placebo; Single dose intravenous infusion of 0.9% sodium chloride injection; Other Names: Intravenous infusion of 0.9% sodium chloride injection
ACTIVE_COMPARATOR: Control: Human Serum Albumin(HSA); Subjects received Human Serum Albumin, 10 g for each day, three days for a cycle, and totally three cycles.	Drug: human albumin injection; multiple doses of intravenous infusion; Other Names: Intravenous infusion of human albumin injection
EXPERIMENTAL: Experimental:recombinant human albumin; Subjects received recombinant Human Serum Albumin, 1.25g, 5g, 10g, 20g, 30 g for the single dose study. For the multiple dose study, subjects received recombinant Human Serum Albumin, 10 g for each day, three days for a cycle, and totally three cycles.	Drug: recombinant human albumin injection; single dose or multiple doses of intravenous infusion; Other Names: Intravenous infusion of recombinant human albumin injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerance	AE	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters	Maximum Plasma Concentration（Cmax）	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.
PK parameters	time to Maximum Plasma Concentration（Tmax）	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.
PK parameters	half life (t1/2）	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.
Pharmacodynamic parameters	Red blood cell specific volume	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.
Pharmacodynamic parameters	Plasma colloid osmotic pressure	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.
Immunogenicity	Percentage of patients with positive reaction	Day 1-Day 57 for single doses study. Day 1-Day 106 for multiple doses study.

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 24, 2019
• Primary Completion (ACTUAL): May 6, 2020
• Study Completion (ACTUAL): May 6, 2020

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (ACTUAL): November 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2020
• Last Update Submitted That Met QC Criteria: November 20, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites
• Other Study ID Numbers: ART-2019-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No