Comparative Immunogenicity Study of Multiple Doses of Proposed Pegfilgrastim Biosimilar, INTP5 of Intas Pharmaceuticals Ltd., India Against Neulasta of Amgen Inc., USA in Healthy, Adult Human Subjects.

NCT04015232 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 0554-17
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The study was an assessor-blind, balanced, parallel, randomized, two-treatment, comparative immunogenicity study of multiple doses of subcutaneous (SC) Pegfilgrastim injection (6 mg/0.6 mL; Intas Pharmaceuticals Ltd. proposed biosimilar INTP5 compared to innovator product, US-Neulasta) in healthy, adult, human subjects under fed conditions.

Conditions

Immunogenicity; Healthy Volunteers

Keywords

Pegfilgrastim; Biosimilar; Immunogenicity; Pharmacokinetics; Pharmacodynamics; Safety; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Immunogenicity Screening Incidence to Detect the Presence of Anti-PegG-CSF Antibodies.

  Immunogenicity (anti-drug antibody; ADA) data is presented for all subjects' samples collected and a descriptive analysis is provided for immunogenicity (ADA) data. Percentage incidence within + 10% of the expected ADA positivity incidence of Test (6% ADA in Test is anticipated from literature) is not considered clinically significant. Evaluation of immunogenicity is carried out in a tiered fashion: 1. Screening assay to assess if samples were positive or negative for anti-PegG-CSF. 2. Confirmatory assays for samples that were positive in the screening assay. The confirmatory assays assessed if antibodies were specific for INTP5, Neulasta, PEG and/or filgrastim. 3. Titer assay was performed to determine titer of the anti-PEG-GCSF antibody samples. 4. Neutralizing antibody (NAb) assay for those samples that were positive in the confirmatory assays to assess the neutralizing capability of the antibody to inhibit pegfilgrastim activity.

  Samples (8 mL each) were withdrawn at screening, at pre-dose and at 336 (D-15, Week 2), 504 (D-22, Week 3, within 60 minutes before 2nd dose), 840 (D-36, Week 5), 1176 (D-50, Week 7), 1680 (D-71, Week 10) and 2016 (D-85, Week 12) hours after first dose.

Secondary Outcomes (16)

• PK Endpoints: Pegfilgrastim C[Max]

  Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

• PK Endpoints: Pegfilgrastim AUC[0-t]

  Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

• PK Endpoints: Pegfilgrastim AUC[0-∞]

  Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

• PK Endpoints: Pegfilgrastim T[Max]

  Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

• PK Endpoints: Pegfilgrastim λz (Lambda-z)

  Venous blood samples (4 mL each) were withdrawn at pre-dose and at 8, 16, 24 (Day 2), 48 (Day 3), 72 (Day 4), 96 (Day 5), 120 (Day 6), 144 (Day 7), 240 (Day 11), 336 (Day 15) and 504 (Day 22) hours following 1st and 2nd dose, administration.

Study Arms (2)

INTP5 biosimilar product

EXPERIMENTAL

INTP5 subcutaneously at a dose of 6 mg/0.6 mL.

Combination Product: INTP5

US Neulasta reference product

ACTIVE COMPARATOR

US Neulasta subcutaneously at a dose of 6 mg/0.6 mL.

Combination Product: US Neulasta

Interventions

INTP5 COMBINATION_PRODUCT

INTP5, a pegfilgrastim biosimilar to US Neulasta.

INTP5 biosimilar product

US Neulasta COMBINATION_PRODUCT

US Neulasta: FDA approved pegfilgrastim innovator product.

US Neulasta reference product

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal, healthy adult human volunteers between 18 to 45 years of age (both inclusive) living in and around Ahmedabad city or western part of India.
• Having body weight ≥50 kg and body mass index (BMI) between 18.5 and 29.9 (both inclusive), calculated as weight in kg/height in meter\^2.
• Not having any significant disease in medical history or clinically significant abnormal findings during screening, abdominal ultrasonography, medical history, clinical examination, laboratory evaluations, 12-lead echocardiogram (ECG) and chest X-ray (posterior-anterior view; within the last 6 months) recordings.
• Able to understand and comply with the study procedures, in the opinion of the investigator.
• Able to give voluntary written informed consent for participation in the trial.
• In case of female subjects:
• Surgically sterilized at least 6 months prior to study participation; Or If a woman of child bearing potential is willing to use a suitable and effective double barrier contraceptive method or intra uterine device during the study.
• Serum pregnancy test (for female subjects) must be negative.

You may not qualify if:

• Known hypersensitivity to the study drug or its constituents and/or hypersensitivity to E. coli derived proteins, and/or previous exposure to the study drug.
• History or presence of any disease or condition which might compromise the haemopoietic, renal, hepatic, endocrine, pulmonary, central nervous, cardiovascular, immunological, dermatological, gastrointestinal or any other body system.
• Known case of hereditary fructose intolerance.
• Subjects with latex allergies will be excluded as the needle cover on the single-use prefilled syringe contains dry natural rubber (latex).
• Any clinically significant laboratory finding including absolute neutrophil count (ANC), platelet, red blood cells (RBC) count, and hemoglobin level at the time of screening.
• Prior exposure to any peptide colony stimulating or growth factor, including erythropoietin, filgrastim or Pegfilgrastim; Prior exposure to any vaccines, immunoglobulin preparations or immunomodulators within the past 6 months prior to receiving first dose; evidence of E. coli diarrhea or diseases within 3 months.
• Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or NSAIDs induced urticaria.
• Subjects with a history of pulmonary infiltrate or pneumonia in the last 6 months.
• History of any hematologic disease including sickle cell disorders.
• Ingestion or use of any prescribed medication at any time within 1 month prior to receiving first dose.
• Receipt of over-the-counter medicines which have not yet cleared from the body (5 half-lives must have passed for the medicine to be considered to have cleared from the body).
• A recent history of harmful use of alcohol, i.e. alcohol consumption of more than 14 standard drinks per week for men and more than 7 standard drinks per week for women (A standard drink is defined as 360 mL of beer or 150 mL of wine or 45 mL of 40% distilled spirits, such as rum, whisky, brandy etc.) or consumption of alcohol or alcoholic products within 72 hours prior to receiving study medicine.
• Smokers, who smoke 10 or more than 10 cigarettes/day or inability to abstain from smoking during the study.
• Use of any recreational drugs or history of drug addiction or testing positive in pre-study drug scans.
• Donation of blood (1 unit or 350 mL) or equivalent amount of blood substitute.

Sponsors & Collaborators

• Intas Pharmaceuticals, Ltd.: lead
• Lambda Therapeutic Research Ltd.: collaborator

Study Sites (1)

Lambda Therapeutic Research Ltd.

Ahmedabad, Gota, 382481, India

Location

Results Point of Contact

• Title: Dr. Adarsh Kumar Garg, M.B.B.S. Principal Investigator
• Organization: Lambda Therapeutic Research Ltd.

adarshgarg@lambda-cro.com

+91-79-40202020

Study Officials

• Adarsh K Garg, M.B.B.S

  Lambda Therapeutic Research Ltd.

  PRINCIPAL INVESTIGATOR

• Vinu Jose, M.D.

  Intas Pharmaceuticals, Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study staff taking care of subject's safety and the laboratory personnel doing the sample analysis of PK, PD, and immunogenicity data were blinded
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: February 26, 2018
• Primary Completion: June 5, 2018
• Study Completion: June 5, 2018
• Last Updated: October 4, 2019
• Results First Posted: October 4, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)