A Clinical Study With Adalimumab Biosimilar

A Randomized, Double-blind, Parallel Groups, Phase 1 Clinical Study Comparing the Pharmacokinetic, Safety and Immunogenicity of Adalimumab in Healthy Subjects

The study aims to evaluate the pharmacokinetic profile, safety profile, and immunogenic potential of adalimumab of a new citrate-free formulation of adalimumab (Adalimumab Richmond) [Test Product] vs. Humira® AC Pen [Reference Product]

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Safety Issues
• Intervention / Treatment: Biological: Humira® (adalimumab) AC Pen [Reference Product]; Biological: Adalimumab Richmond [Test Product]

Detailed Description

This is a phase 1 pharmacokinetic, safety and immunogenicity comparative, single-dose, double-blind, randomized, balanced parallel-group clinical study conducted in healthy subjects of both sexes.

Blood samples are collected for up to 71 days to determine the quantification of adalimumab and for 12 months for antidrug antibody detection. Safety and tolerability are also assessed.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425BAA
    • FP Clinical Pharma S.R.L.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Written and signed informed consent

   • Study subjects must be able to understand and comply with the protocol.
   • Study subjects must be willing and able to provide written informed consent.

2. Target population

   • Study subjects, volunteers, adults, healthy.
   • Study subjects with normal physical examination or with findings that, in the investigator's opinion, have no clinical relevance.
   • Study subjects whose safety and complementary laboratory tests are within normal values or who, in the investigator's opinion, have no clinical relevance.
   • Body mass index between 19 and 27 kg/m2 at the screening visit.
   • Study subjects preferably non-smokers. Smokers must refrain from smoking during the clinical research protocol.
   • Study subjects should not have a history of drug and/or alcohol abuse.

3. Age and gender

   • Women and men, from 21 to 55 years of age.
   • Women must not be pregnant. Women must use adequate non-hormonal contraception to prevent pregnancy throughout the clinical investigation protocol [and for a period of not less than 5 months after the last dose of the investigational product].
   • Men with a partner of childbearing potential must agree that their partner use adequate contraception prior to study entry [and for a period of not less than 5 months after the last dose of investigational product]. An adequate contraceptive method is understood to be any hormonal contraceptive method or intrauterine device (which must be established before the start of the study) and the use of a spermicide as a barrier method. Use of a barrier method alone or sexual abstinence is not considered appropriate.
   • Subjects must agree not to donate sperm during the study and for 5 months after treatment.

Exclusion Criteria:

1. Medical history and concurrent illnesses

   • History of cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, endocrine-metabolic, neurological disease or conditions of psychiatric origin (depressive disorders, in particular) at the time of taking the history and physical examination during the first visit of the clinical research protocol.
   • History of allergic drug reactions of any kind.
   • History of orthostatic hypotension.
   • Blood donation within 3 months prior to screening.
   • Participation in another clinical pharmacology study in the last 3 months.
   • History and/or current history of clinically significant diseases or disorders that, in the investigator's opinion, may prevent the participation of the study subject for safety reasons or that may influence the results of the study as well as the capacity of the study subject. to participate in the clinical research protocol.
   • History of hypersensitivity to adalimumab and/or any of the excipients.
   • Previous exposure to a biological product.

2. Physical findings and laboratory tests

   • Cardiac, pulmonary, gastrointestinal, hepatic, renal, haematological, endocrine-metabolic, neurological disease or conditions of psychiatric origin (depressive disorders, in particular).
   • Clinically significant abnormalities in any laboratory tests
   • Positive serology for HIV, hepatitis B, hepatitis C.

3. Sex and reproductive condition

   - Women of childbearing potential who are unwilling or unable to use an adequate non-hormonal method of contraception throughout the clinical investigation protocol [and for a period of not less than 5 months after the last dose of the investigational product].

4. Allergies, adverse drug reactions and contraindications

   - Study subjects with allergies, adverse drug reactions or contraindications to therapy.

5. Prohibited treatments and/or therapies

   - The study subjects must have suspended any drug treatments at least 2 weeks before starting this clinical research protocol.

6. Other exclusion criteria

   • Non-cooperative study subjects.
   • Study subjects employed by the investigator or the Clinical Pharmacokinetic Research Unit, with direct participation in the clinical investigation protocol or other clinical protocols under the direction of the Investigator or the Clinical Pharmacokinetic Research Unit.

The eligibility criteria for this clinical research protocol have been considered to guarantee the safety of the study subjects and ensure that their results can be used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Humira® (adalimumab) AC Pen [Reference Product]; A single subcutaneous dose of 40 mg of the Reference Product- Humira® AC Pen [Reference Product]	Biological: Humira® (adalimumab) AC Pen [Reference Product]; A single subcutaneous dose
Active Comparator: Adalimumab Richmond [Test Product]; A single subcutaneous dose of 40 mg of the Test Product- Adalimumab Richmond [Test Product]	Biological: Adalimumab Richmond [Test Product]; A single subcutaneous dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Serum Concentration of adalimumab (Cmax)	Cmax will be obtained directly from the serum concentration-time curve	Pre-dose: 0.00; Post-dose: 4.0; 8.0; 12.0; 24.0; 48.0; 72.0; 96.0; 120.0; 144.0; 168.0; 192.0; 336.0; 504.0; 672.0; 840.0; 1008.0; 1344.0; 1680.0 hours
Area Under the Serum Concentration-time Curve of adalimumab (ABC0-t)	Area under the serum concentration-time curve from time zero to the last experimental point, will be calculated by the trapezoidal rule	Day 1 to Day 71
Area Under the Serum Concentration- Time Curve ob adalimumab (ABC0-∞)	Area under the serum concentration- time curve from time zero to infinity	Day 1 to Day 71

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of samples with positive Anti-adalimumab serum antibodies	Anti-adalimumab serum antibodies detection	Screening, post dose: 672.0 hours, 1680.0 hours, 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Report the nature and incidence of adverse events and the eventual suspension or abandonment of the study or the participation of a study subject.	Day 1 to Day 71
Number of positive Anti-adalimumab serum samples with neutralizing capacity	To determine the neutralizing capacity of anti-adalimumab antibody positive samples	Screening, post dose: 672.0 hours, 1680.0 hours, 12 months

Collaborators and Investigators

• Sponsor: Laboratorios Richmond S.A.C.I.F.
• Collaborators: FP Clinical Pharma S.R.L.; Custom Biologics
• Investigators: Principal Investigator: Ethel C. Feleder, MD, FP Clinical Pharma S.R.L.

Publications and helpful links

General Publications

• International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use.. ICH harmonized tripartite guideline: Guideline for Good Clinical Practice. J Postgrad Med. 2001 Jan-Mar;47(1):45-50. No abstract available.
• Lembach J, Skerjanec A, Haliduola H, Hass N, von Richter O, Fuhr R, Koernicke T. Randomized, Double-Blind, Single-Dose, Three-Arm Parallel Trial to Determine the Pharmacokinetics and Safety of GP2017, EU- and US-Adalimumab in Healthy Male Subjects. Arthritis Rheumatol, 69(10), 2017
• Wynne C, Altendorfer M, Sonderegger I, Gheyle L, Ellis-Pegler R, Buschke S, Lang B, Assudani D, Athalye S, Czeloth N. Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE(R)-PK) in healthy subjects. Expert Opin Investig Drugs. 2016 Dec;25(12):1361-1370. doi: 10.1080/13543784.2016.1255724.

Helpful Links

• PubMed ID: 11590294
• A Randomized, Double-Blind, Single-Dose, Three-Arm Parallel Trial to Determine the Pharmacokinetics and Safety of GP2017, EU- and US-Adalimumab in Healthy Male Subjects.
• PubMed ID: 27813422

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): October 20, 2023

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Bioequivalence; Immunogenicity; adalimumab; Crohn's disease; Ulcerative colitis; Psoriatic arthritis; Rheumatoid arthritis; Biosimilar; Plaque psoriasis; Non-infectious uveitis; Hidradenitis suppurativa; Ankylosing Spondylitis (AS); Non-radiographic axial spondyloarthritis; Enthesitis-related arthritis; Behcet's Intestinal Disease; Adults, healthy, of both sexes
• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Antirheumatic Agents; Tumor Necrosis Factor Inhibitors; Adalimumab
• Other Study ID Numbers: 0225

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