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

• Status: Recruiting
• Trial end date: 2022-04-30
• Target enrollment: 0
• Participant gender: All

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. 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

(B): Humira 40 mg/ 0.4ml of Abbvie Ltd in normal, healthy, adult, human subjects in a Parallel group study.

2. To evaluate the safety between two products.

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).

Specific objectives-

1. 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%.

2. Safety assessment: Evaluation and comparison between references vs. test drug in terms of safety end point.

3. Efficacy assessment: The primary endpoints will be -

1. Proportion of patients with an ACR20 response in both the treatment groups at week 12.

2. Evaluation and comparison of safety between references vs. test drug.

The secondary endpoints will be -

1. Change in Disease Activity Score of 28 joints - CRP (DAS28-CRP),

2. Proportion of patient with an ACR50 response and

3. Proportion of patients with an ACR70 response in both the treatment groups at week 12.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Institute for Developing Science and Health Initiatives, Bangladesh
• Collaborators: Green Life Center for Rheumatic Care & Research, Bangladesh; Universal Medical College Hospital, Bangladesh
• Treatments: Adalimumab

Criteria

Inclusion Criteria:

1. Eligibility of ages for Study: ≥ 18 Years to ≤ 45 Years

2. Genders Eligible for Study: Both

3. Subjects who are able and willing to give written informed consent

4. 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.

Exclusion Criteria:

1. 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).

2. Previous history of cancer, except for adequately treated basal cell or squamous cell carcinoma of the skin.

3. Active or latent Tuberculosis or who have a history of Tuberculosis

4. History of invasive systemic fungal infections or other opportunistic infections

5. Systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process

6. Serious infection associated with hospitalization and/or which required intravenous antibiotics

7. History of and/or current cardiac disease or moderate to severe heart failure (NYHA class III/IV).

8. 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

9. Intake medication with a half-life > 24 h within 4 weeks or 5 half-lives of the medication prior to investigational product administration

10. Hypersensitivity to the active substance or to any of the excipients (Mannitol and Polysorbate 80)

11. History of severe allergic or anaphylactic reactions to latex

12. History of alcohol, drug, or chemical abuse within 6 months prior to screening

13. History of chronic daily use of narcotic analgesics.