Hulio Interchangeability to Humira®, Comparing Pharmacokinetics, Efficacy, Safety and Immunogenicity

Phase 3

Completed

• Conditions: Moderate Chronic Plaque Psoriasis; Severe Chronic Plaque Psoriasis
• Interventions: Biological: Hulio 40 MG in Prefilled Syringe / Humira 40 MG in Prefilled Syringe; Biological: Humira 40 MG in Prefilled Syringe

• Registration Number: NCT05637515
• Lead Sponsor: Biocon Biologics Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-21
• Study First Submitted: 2022-11-23
• Study First Submitted QC: 2022-11-23
• Study First Posted: 2022-12-05
• Primary Completion: 2023-09-19
• Study Completion: 2023-09-19
• Results First Submitted: 2024-09-19
• Results First Submitted QC: 2024-09-19
• Status Verified: 2024-10
• Results First Posted: 2024-10-15
• Last Update Submitted: 2024-10-20
• Last Update Posted: 2024-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 374

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Repeated switches Humira - Hulio	Hulio 40 MG in Prefilled Syringe / Humira 40 MG in Prefilled Syringe	Subjects will receive Humira in Run-in period \& undergo repeated switches between Humira Hulio during randomized interchangeable treatment period Randomized interchangeable treatment period: * Subjects undergo repeated switches between Humira and Hulio between week 12 to week 26. * 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.
Humira continuously	Humira 40 MG in Prefilled Syringe	Subjects receive Humira continuously both during Run-in period and Randomized interchangeable treatment period. Run-in Period: 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). Randomized interchangeable treatment period: Subjects continue to receive Humira (40 mg every other week) until Week 26

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (36)

Site 203 - North Estonia Medical Centre Foundation; 🇪🇪 Talinn, Estonia

Site 205 - OÜ Innomedica; 🇪🇪 Tartu, Estonia

Site 105 - Twoja Przychodnia-Szczecinskie Centrum Medyczne; 🇵🇱 Szczecin, Poland

Site 406 - Medical Center Unimed Eood; 🇧🇬 Sevlievo, Bulgaria

Site 407 - Medical Centre "Asklepii", OOD; 🇧🇬 Dupnitsa, Bulgaria

Site 402 - DCC "Alexandrovska", EOOD; 🇧🇬 Sofia, Bulgaria

Site 201 - Tartu University Hospital; 🇪🇪 Tartu, Estonia

Site 114 - ETG Skierniewice; 🇵🇱 Skierniewice, Poland

Site 409 - Medical center Medconsult Pleven OOD; 🇧🇬 Pleven, Bulgaria

Site 204 - Clinical Research Centre; 🇪🇪 Tartu, Estonia

Site 116 - FutureMeds Krakow; 🇵🇱 Kraków, Poland

Site 401 - Ambulatory for Specialized Medical Help - skin and venereal diseases; 🇧🇬 Sofia, Bulgaria

Site 404 - DCC Focus 5 - MEOH OOD; 🇧🇬 Sofia, Bulgaria

Site 106 - ETG Lodz; 🇵🇱 Łódź, Poland

Site 107 - MICS Centrum Medyczne Warszawa; 🇵🇱 Warsaw, Poland

Site 108 - Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna; 🇵🇱 Łódź, Poland

Site 117 - MCM POLIMEDICA; 🇵🇱 Warsaw, Poland

Site 120 - Twoja Przychodnia PCM; 🇵🇱 Posen, Poland

Site 403 - MC Rusemed ltd.; 🇧🇬 Ruse, Bulgaria

Site 405 - Medical Center Hera EOOD; 🇧🇬 Sofia, Bulgaria

Site 408 - DCC "Alexandrovska", EOOD; 🇧🇬 Sofia, Bulgaria

Site 410 - DCC XXVIII; 🇧🇬 Sofia, Bulgaria

Site 304 - CCR Ostrava s.r.o.; 🇨🇿 Ostrava, Czechia

Site 303 - CCR Czech, a.s.; 🇨🇿 Pardubice, Czechia

Site 301 - Kozni Ambulance Fialova s.r.o.; 🇨🇿 Praha, Czechia

Site 302 - CLINTRIAL s.r.o.; 🇨🇿 Praha, Czechia

Site 111 - SPECDERM POZNANSKA; 🇵🇱 Białystok, Poland

Site 103 - Centrum Medyczne Pratia Bydgoszcz; 🇵🇱 Bydgoszcz, Poland

Site 104 - Clinic Med Daniluk, Nowak Spółka Jawna; 🇵🇱 Białystok, Poland

Site 101 - Centrum Kliniczno - Badawcze J. Brzezicki, B. Górnikiewicz-Brzezicka Lekarze Spółka Partnerska; 🇵🇱 Elbląg, Poland

Site 109 - Centrum Badan Klinicznych P.I. House Sp. z o.o.; 🇵🇱 Gdańsk, Poland

Site 112 - CENTRUM MEDYCZNE ALL-MED; 🇵🇱 Kraków, Poland

Site 115 - ETG Lublin; 🇵🇱 Lublin, Poland

Site 113 - ai centrum medyczne sp. z o.o. sp.k.; 🇵🇱 Poznań, Poland

Site 118 - ETG Siedlce; 🇵🇱 Siedlce, Poland

Site 110 - Clinical Research Group Sp. z o.o.; 🇵🇱 Warsaw, Poland