A Randomized, Double-blinded, Active Controlled Crossover Clinical Trial to Investigate PK, PD and Safety of GBPD002

NCT05585658 | Completed Phase 1 DMC

• 1 other identifier: DGDA/CTP-1/06/2016/9916
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

Erythropoietin (EPO) biosimilarity for GBPD002 (test candidate) and Eprex® (comparator) has been evaluated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties following subcutaneous injection in human subjects. This was a randomized, double-blind, two-sequence, crossover study. Subjects were randomly assigned and received a dose (4,000 IU) of either the test or comparator EPO. The subjects received the alternative formulation after the wash out period (4 weeks) of the first administration. The primary PK parameters, viz., maximum observed concentration (Cmax) and area under the curve extrapolated to infinity (AUC00-inf), were calculated with the serum EPO concentrations from blood samples and were found comparable for both formulations. The geometric mean ratios (@90% CI) of the Cmax and AUCinf were 1.16 and 0.89, respectively, which were within the regulatory range of 0.80-1.25. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured as PD markers. The time-matched serum EPO concentrations and PD markers denoted a counterclockwise hysteresis, and thereby suggesting a time delay between the observed concentration and the response. ANOVA derived P-values (all were greater than 0.05) for the effectors clearly revealed the similarity between effects on PD markers for both formulations. Both formulations were found tolerated well, and anti-drug antibodies were not observed. Thus, the two formulations are projected to be used interchangeably in clinical settings.

Conditions

Natural Blood and Blood Product Toxicity

Keywords

human recombinant erythropoietin

Outcome Measures

Primary Outcomes (1)

• Primary endpoint to measure safety, efficacy and acceptability of Erythropoietin medicine

  EDTA-containing tube needs to be arranged for whole blood collection; for each test \~350 µL sample may require.Area under Curve last (AUC0-last) of Erythropoietin: Area Under Curve last (AUC0-last) of Erythropoietin \[Time Frame: Once 1 hour before administration (day 1/day 29); 1, 3, 6, 8, 10, 14, 24, 48, 72, 96, 120, 144 (day 6/day 34) hrs after administration for each period\]

  34 days

Secondary Outcomes (1)

• Secondary endpoints to measure safety, efficacy and acceptability of Erythropoietin medicine

  34 days

Study Arms (2)

Erythropoietin alpha Eprex®

ACTIVE COMPARATOR

Group/cohort/Arm 1 (participating 21 volunteers): Eprex® injection 4,000 IU will be administered subcutaneously on Day 1; and wash out for 4 weeks. GBPD002 injection 4,000 IU/1 mL will be administered subcutaneously on Day 29.

Biological: Erythropoietin alpha

Erythropoietin alpha, GBPD002

EXPERIMENTAL

Group/cohort/Arm 2 (participating 21 volunteers):GBPD002 PFS (Pre-Filled Syringe) 4,000 IU/ 1 mL (Erythropoietin alfa 4,000 IU) will be administered subcutaneously on Day 1.And wash out for 4 weeks (28 days from the 1st injection day). Eprex® inj. (Injection) 4,000 IU (Erythropoietin alfa 4,000 IU) will be administered subcutaneously on Day 29. Total 42 volunteers participated in the clinical trial.

Biological: Erythropoietin alpha

Interventions

Erythropoietin alpha BIOLOGICAL

To analyze bio-similarity of GBPD002 with Eprex®, the Globe Biotech Ltd performed quite a few experiments to determine total analytical study of GBPD002. They performed peptide mapping to determine amino acid composition of GBPD002 and found similar result with erythropoietin alpha. The molecular weight was determined through SDS-PAGE analysis of GBPD002 and was compared with Eprex. The western blot analysis was performed to determine immune chemical characterization. Characterization of different isoforms was conducted through 2D gel electrophoresis.

Erythropoietin alpha Eprex®; Erythropoietin alpha, GBPD002

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: The inclusion criteria of subjects for the study are following Age: 18 - 45 years; Body Mass Index (BMI): 18.0 - 27.0 kg/m2
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• age:18 - 45 years;
• BMI:18.0 - 27.0 kg/m2;
• body weight: 55 - 90 kg;
• able to swallow tablets,
• clinically and mentally fit subjects having no comorbid disease condition such as ISD, heart failure, CKD, Alzheimer's diseases, liver cirrhosis.

You may not qualify if:

• Hemoglobin level below 12 g/dL or over 17g/dL,
• Vitamin B12 level below 200 pg/mL,
• Ferritin level below 21.8 ng/mL,
• Transferrin level below 190 mg/dL,
• Reticulocyte, erythrocytes,
• insulin dependent diabetes,
• Thyroid disease, platelets or serum potassium level over/below normal range.

Sponsors & Collaborators

• Globe Biotech Limited: lead

Study Sites (2)

Globe Biotech Limited

Dhaka, 1208, Bangladesh

Location

Farabi General Hospital

Dhaka, 1209, Bangladesh

Location

MeSH Terms

Interventions

Epoetin Alfa

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Mamun Al Mahtab, PhD

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or subjects. The following study procedures will be in place to ensure double-blind administration of study treatments. Blinded (investigators) and unblinded (study nurses responsible for administration of study medication) study personnel had to be involved in order to preserve blinding of the investigator.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Healthy volunteers participating in two cohorts. In each cohort 21 volunteers are participating in the clinical trial.

Study Record Dates

• First Submitted: September 25, 2022
• First Posted: October 19, 2022
• Study Start: October 16, 2021
• Primary Completion: November 14, 2021
• Study Completion: December 16, 2021
• Last Updated: October 20, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

BA (2)