Study to Compare PK & Safety of Advixa With Humira in Healthy, Adult Subject Followed by Efficacy & Safety Study in RA Patients

NCT05172817 | Unknown Phase 2 DMC

• 1 other identifier: IDE-21-005
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Adalimumab is a recombinant monoclonal antibody (IgG1 subclass) against human TNF-α (Tumor Necrosis Factor-alpha). It is an immunosuppressive medication predominantly used to treat rheumatoid arthritis autoimmune disease. It is also used for the treatment of psoriatic arthritis, ankylosing spondylitis, and Crohn's disease etc. Adalimumab binds specifically to TNF-α and blocks its general cytokine effects, thereby reducing TNF-induced inflammation and halting tissue destruction. Adalimumab was approved for medical use in the United States in 2002. It is on the World Health Organization's List of Essential Medicines. It is available as a biosimilar medication. In 2017, it was the 169th most commonly prescribed medication in the United States, with more than three million prescriptions. Adalimumab is an expensive product which is indicated in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, etc. Each patient will be provided the study drug free of cost in this study which will benefit them immensely. The advent of therapeutic monoclonal antibodies has given a major boost to the treatment of individuals suffering from autoimmune disorders, including rheumatoid arthritis. Adalimumab is one such therapeutic monoclonal antibody used for treatment of rheumatoid arthritis marketed with brand name Humira by Abbvie Ltd. (USA) was the only adalimumab biosimilar available for patients in Bangladesh until recently. Incepta Pharmaceuticals Ltd. Bangladesh has introduced Bangladesh's first locally manufactured adalimumab biosimilar Advixa that is available at a fraction of Humira's cost. This study aims to evaluate the pharmacokinetics, safety and efficacy of the Adalimumab biosimilar (Advixa) in comparison to Adalimumab (Humira) as reference. The biosimilar Advixa being a local product will a cost-effective alternative to imported drugs currently available in the market. Objectives of the Protocol General objectives-

1. 1.To assess the Pharmacokinetic between Test Product (A): Adalimumab (Advixa) 40 mg/ 0.4 ml of Incepta Pharmaceuticals Ltd of Bangladesh and the corresponding Reference Product
2. 2.To evaluate the safety between two products.
3. 3.To assess efficacy, tolerability and safety of biosimilar adalimumab (Advixa, Incepta) in compared with reference adalimumab (Humira, AbbVie) in patients with moderate to severe rheumatoid arthritis (RA).
4. 4.Pharmacokinetic (PK) Parameters: For Cmax and AUC0-t the 90% confidence interval for the ratio of the test and reference products should be contained within the acceptance interval of 80.00-125.00%.
5. 5.Safety assessment: Evaluation and comparison between references vs. test drug in terms of safety end point.
6. 6.Efficacy assessment: The primary endpoints will be -
7. 7.Proportion of patients with an ACR20 response in both the treatment groups at week 12.
8. 8.Evaluation and comparison of safety between references vs. test drug.
9. 9.Change in Disease Activity Score of 28 joints - CRP (DAS28-CRP),
10. 10.Proportion of patient with an ACR50 response and
11. 11.Proportion of patients with an ACR70 response in both the treatment groups at week 12.

Conditions

Pharmacokinetics; Safety; Efficacy; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Peak Plasma Concentration (Cmax) of 40 participants will be measured and reported

  For "Peak Plasma Concentration (Cmax)", the 90% confidence interval for the ratio of the test and reference products should be contained within the acceptance interval of 80.00-125.00%. and evaluation and comparison between references vs. test drug in terms of safety end point.

  6 months

• Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) of 40 participants will be measured and reported

  For "Area under the plasma concentration versus time curve (AUC)" , the 90% confidence interval for the ratio of the test and reference products should be contained within the acceptance interval of 80.00-125.00%. and evaluation and comparison between references vs. test drug in terms of safety end point.

  6 months

• For efficacy assessment of 160 patients of Rheumatoid Arthritis, ACR 20 response will be measured and reported in outcome measures result data table

  Proportion of patients with an ACR20 response in both the treatment groups at week 12 as well as safety between references vs. test drug should be observed.

  6 months

Study Arms (2)

Advixa

EXPERIMENTAL

Generic name: Adalimumab Dosage form: Injectable Route of Administration: Subcutaneous Dosage: 40mg/0.4mL Frequency: Once in 2 weeks Duration: Single dose for Phase 2 and 3 months for Phase 3

Drug: Advixa (Adalimumab)

Humira

ACTIVE COMPARATOR

Generic name: Adalimumab Dosage form: Injectable Route of Administration: Subcutaneous Dosage: 40mg/0.4mL Frequency: Once in 2 weeks Duration: Single dose for Phase 2 and 3 months for Phase 3

Drug: Advixa (Adalimumab)

Interventions

Advixa (Adalimumab) DRUG

Injection Advixa(Adalimumab) 40 mg/ 0.4 ml will be administered subcutaneously to the participants by trained medical personnel. Single dose for phase 2 and biweekly for 3 months for phase 3.

Advixa; Humira

Eligibility Criteria

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

You may qualify if:

• Eligibility of ages for Study: ≥ 18 Years to ≤ 45 Years
• Genders Eligible for Study: Both
• Subjects who are able and willing to give written informed consent
• Willing and able to comply with the requirements of the protocol and be available for the planned duration of the study.
• d. Have Chest X ray with no evidence of current active TB or previous (inactive) TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or prior to study and read by a qualified radiologist.
• e. Female patients of childbearing potential have to have a negative pregnancy test at the time of screening and agreed to use adequate contraception throughout the study period.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (Multiple sclerosis), autoimmune, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Previous history of cancer, except for adequately treated basal cell or squamous cell carcinoma of the skin.
• Active or latent Tuberculosis or who have a history of Tuberculosis
• History of invasive systemic fungal infections or other opportunistic infections
• Systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process
• Serious infection associated with hospitalization and/or which required intravenous antibiotics
• History of and/or current cardiac disease or moderate to severe heart failure (NYHA class III/IV).
• Have received live vaccine(s) within 4 weeks prior to Screening or who will require live vaccine(s) between Screening and the final study visit
• Intake medication with a half-life \> 24 h within 4 weeks or 5 half-lives of the medication prior to investigational product administration
• Hypersensitivity to the active substance or to any of the excipients (Mannitol and Polysorbate 80)
• History of severe allergic or anaphylactic reactions to latex
• History of alcohol, drug, or chemical abuse within 6 months prior to screening
• History of chronic daily use of narcotic analgesics.

Sponsors & Collaborators

• Institute for Developing Science and Health Initiatives, Bangladesh: lead
• Universal Medical College Hospital, Bangladesh: collaborator
• Green Life Center for Rheumatic Care & Research, Bangladesh: collaborator
• Incepta Pharmaceuticals Ltd, Bangladesh: collaborator

Study Sites (1)

ideSHi

Dhaka, 1212, Bangladesh

RECRUITING

Related Publications (3)

• van Schouwenburg PA, van de Stadt LA, de Jong RN, van Buren EE, Kruithof S, de Groot E, Hart M, van Ham SM, Rispens T, Aarden L, Wolbink GJ, Wouters D. Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients resulting in functional neutralisation. Ann Rheum Dis. 2013 Jan;72(1):104-9. doi: 10.1136/annrheumdis-2012-201445. Epub 2012 Jul 3.

  PMID: 22759910 BACKGROUND

• Jani RH, Gupta R, Bhatia G, Rathi G, Ashok Kumar P, Sharma R, Kumar U, Gauri LA, Jadhav P, Bartakke G, Haridas V, Jain D, Mendiratta SK. A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis. Int J Rheum Dis. 2016 Nov;19(11):1157-1168. doi: 10.1111/1756-185X.12711. Epub 2015 Jul 14.

  PMID: 26176644 BACKGROUND

• Jamshidi A, Gharibdoost F, Vojdanian M, Soroosh SG, Soroush M, Ahmadzadeh A, Nazarinia MA, Mousavi M, Karimzadeh H, Shakibi MR, Rezaieyazdi Z, Sahebari M, Hajiabbasi A, Ebrahimi AA, Mahjourian N, Rashti AM. A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA(R)) to the reference product (Humira(R)) in patients with active rheumatoid arthritis. Arthritis Res Ther. 2017 Jul 20;19(1):168. doi: 10.1186/s13075-017-1371-4.

  PMID: 28728599 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zannat Kawser, M.Phil.

  institute for developing Science and Health initiatives

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Firdausi Qadri, Ph.D.

CONTACT

+8801711595367; fqadri333@gmail.com

Mohabbat Hossain, M.Sc

CONTACT

+8801799390066; mohabbat@ideshi.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: December 29, 2021
• Study Start: June 2, 2021
• Primary Completion: November 30, 2021
• Study Completion: October 30, 2022
• Last Updated: July 7, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)