Moderate Chronic Plaque Psoriasis, Severe Chronic Plaque Psoriasis
Conditions
Keywords
adalimumab, pharmacokinetics, plaque psoriasis
Brief summary
Hulio is a monoclonal antibody currently approved as a biosimilar to European Union approved and United States (US)-Licensed Humira. This is a multicenter, randomized blinded, parallel group, interchangeability study in subjects with moderate to severe chronic plaque psoriasis, undergoing repeated switches between Humira and Hulio. The study is designed to confirm the pharmacokinetic equivalence of alternating between the use of Humira and Hulio and, Humira without such alternation or switch, in accordance with the US Food and Drug Administration Guidance for Industry, Considerations in Demonstrating Interchangeability with a Reference Product. The study will also assess safety, efficacy and immunogenicity between these two groups.
Interventions
BIOLOGICALHumira 40 MG in Prefilled Syringe
Humira (40 mg every other week)
BIOLOGICALHulio 40 MG in Prefilled Syringe / Humira 40 MG in Prefilled Syringe
• Subjects will receive Humira (initial dose of 80 mg \[2 × 40 mg\]; Day 1 administered subcutaneously (SC), followed by 40 mg SC given every other week starting 1 week after the initial dose (last dose at Week 10). Hulio (40 mg every other week) at Week 12 and Week 14 * Humira (40 mg every other week) at Week 16 and Week 18, and * Hulio (40 mg every other week) at Week 20, Week 22, Week 24 and Week 26.
Sponsors
Mylan Inc.
MEDA Pharma GmbH & Co. KG
IQVIA Pvt. Ltd
Biocon Biologics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Able to understand and voluntarily provide written informed consent to participate in the study 2. Aged 18 to 75 years, inclusive, at the time of Screening 3. Has moderate to severe chronic plaque psoriasis for at least 6 months prior to screening and that has involved body surface area ≥10%, PASI ≥12, and static Physicians Global Assessment (sPGA) ≥3 (moderate) at Screening and at Baseline 4. Has stable disease for at least 2 months (i.e., without significant changes as defined by the principal investigator \[PI\] or designee) 5. Is a candidate for systemic therapy or phototherapy 6. Has a previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy, including methotrexate, cyclosporine, psoralen plus ultraviolet light A (PUVA), and ultraviolet light B (UVB) 7. Willing to follow the contraception requirement, based on the childbearing potential.
Exclusion criteria
Subjects must not be enrolled in the study if they meet any of the following criteria: 1. Has been diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, other skin conditions (e.g., eczema), or other systemic autoimmune disorder/ inflammatory disease at the time of the Screening visit that would interfere with evaluations of the effect of the study treatment of psoriasis 2. Prior and concomitant medications: Has prior use of any of the medications specified in the CTP within specified time periods or will require use during the study: 3. Has received live or attenuated vaccines during the 4 weeks prior to Screening or has the intention of receiving a live or attenuated vaccine at any time during the study 4. Other medical conditions: Known chronic or relevant acute TB 5. Has an underlying condition (including, but not limited to, metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious, or gastrointestinal) which, in the opinion of the PI or designee, significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy 6. Has a planned surgical intervention during the duration of the study and which, in the opinion of the PI or designee, will put the subject at further risk or hinder the subject's ability to maintain compliance with study treatment and the visit schedule 7. Has any active and serious infection or history of infections 8. Is positive for human immunodeficiency virus (HIV), hepatitis C virus antibody, or hepatitis B surface antigen (HbsAg) or is positive for hepatitis B core antibody (HbcAb) at Screening 9. Has laboratory abnormalities, including but not limited to clinically significant hematological abnormalities, that, in the opinion of the PI or designee, could cause this study to be detrimental to the subject. The subjects should be excluded if they have the following laboratory abnormalities 1. Hemoglobin \<9 g/dL 2. Platelet count \<100 000/mm3 3. White blood cell count \<3000 cells/mm3 4. Aspartate aminotransferase and/or alanine aminotransferase that is persistently ≥2.5 × the upper limit of normal. (Persistently indicates elevated transaminases, at least on two separate occasions) 5. Creatinine clearance \<50 mL/min (Cockcroft Gault formula) 10. Has severe progressive or uncontrolled, clinically significant disease that in the judgment of the PI or designee renders the subject unsuitable for the study 11. Has moderate to severe heart failure (New York Heart Association \[NYHA\] Class III/IV) 12. Has a history of hypersensitivity to the active substance or to any of the excipients of Humira or Hulio 13. Is pregnant or nursing (lactating) woman 14. Has evidence (as assessed by the PI or designee using good clinical judgment) of alcohol or drug abuse or dependency up to 5 years prior to Screening 15. Is unable to follow study instructions and comply with the protocol in the opinion of the PI or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoints: Pharmacokinetics (PK) - AUC | Week 26 - 28 | AUCτ, 26-28 (Area under the adalimumab concentration-time curve \[AUC\] over the dosing interval of Week 26-28) |
| Primary Endpoints: Pharmacokinetics (PK) - Cmax | Week 26 - 28 | Cmax, 26-28 (Maximum observed adalimumab concentration during the dosing interval Week 26-28). |
Countries
Bulgaria, Czechia, Estonia, Poland
Participant flow
Recruitment details
A total of 374 subjects were randomized into the randomized interchangeable treatment period which comprised of two groups, Group 1 and Group 2. Subjects in Group 1 (N=193), continued to receive Humira (40 mg every other week) until Week 26/Visit 14; While subjects in Group 2 (N=181), underwent multiple switches until Week 26/Visit 14: Hulio (40 mg every other week) for 4 weeks, Humira (40 mg every other week) for 4 weeks, and Hulio (40 mg every other week) for 8 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 :- Humira Continuously Subjects received Humira continuously during both periods:
Run-in Period: Initial Humira 80 mg dose (two 40 mg doses) on Day 1, followed by 40 mg SC every other week from Week 1 to Week 10.
Randomized Interchangeable Treatment Period: 40 mg SC every other week until Week 26/Visit 14. | 193 |
| Group 2 :- Repeated Switches Humira - Hulio Subjects switched between Humira and Hulio:
Run-in Period: Humira 80 mg on Day 1, then 40 mg SC every other week until Week 10.
Randomized Period: Switched treatments until Week 26:
1. Hulio 40 mg every other week for 4 weeks.
2. Humira 40 mg every other week for 4 weeks.
3. Hulio 40 mg every other week for 8 weeks.
Randomization was based on Week 12 PASI response. | 181 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 17 | 17 |
Baseline characteristics
| Characteristic | Group 1 :- Humira Continuously | Group 2 :- Repeated Switches Humira - Hulio | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 20 Participants | 22 Participants | 42 Participants |
| Age, Categorical Between 18 and 65 years | 173 Participants | 158 Participants | 331 Participants |
| Age, Continuous | 46.4 Years STANDARD_DEVIATION 12.86 | 45.7 Years STANDARD_DEVIATION 13.4 | 46.0 Years STANDARD_DEVIATION 13.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants | 179 Participants | 371 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 191 Participants | 181 Participants | 372 Participants |
| Region of Enrollment Bulgaria | 45 participants | 46 participants | 91 participants |
| Region of Enrollment Czechia | 32 participants | 30 participants | 62 participants |
| Region of Enrollment Estonia | 4 participants | 5 participants | 9 participants |
| Region of Enrollment Poland | 112 participants | 100 participants | 212 participants |
| Sex: Female, Male Female | 61 Participants | 69 Participants | 130 Participants |
| Sex: Female, Male Male | 132 Participants | 112 Participants | 244 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 193 | 1 / 181 |
| other Total, other adverse events | 66 / 193 | 54 / 181 |
| serious Total, serious adverse events | 3 / 193 | 3 / 181 |
Outcome results
Primary
Primary Endpoints: Pharmacokinetics (PK) - AUC
AUCτ, 26-28 (Area under the adalimumab concentration-time curve \[AUC\] over the dosing interval of Week 26-28)
Time frame: Week 26 - 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 :- Humira Continuously | Primary Endpoints: Pharmacokinetics (PK) - AUC | 2127.57 h*ug/mL | Standard Deviation 1432.8 |
| Group 2:- Repeated Switches Humira - Hulio | Primary Endpoints: Pharmacokinetics (PK) - AUC | 2357.61 h*ug/mL | Standard Deviation 1636.09 |
Primary
Primary Endpoints: Pharmacokinetics (PK) - Cmax
Cmax, 26-28 (Maximum observed adalimumab concentration during the dosing interval Week 26-28).
Time frame: Week 26 - 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 :- Humira Continuously | Primary Endpoints: Pharmacokinetics (PK) - Cmax | 7.69 ug/mL | Standard Deviation 4.96 |
| Group 2:- Repeated Switches Humira - Hulio | Primary Endpoints: Pharmacokinetics (PK) - Cmax | 8.46 ug/mL | Standard Deviation 5.42 |