Loss of Response of Adalimumab Biosimilar vs Adalimumab Original, in Inflammatory Bowel Disease.

Study Overview
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Brief Summary
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Loss of response of the Adalimumab biosimilar compared with the original drug.

Detailed Description
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A single-site Unicentric, randomized, parallel-group, non-inferiority open study including patients diagnosed with inflammatory bowel disease (Crohn's disease and Ulcerative Colitis) who were in clinical remission with Adalimumab original for at least 6 months prior to the start of the study. A total of 216 patients with inflammatory bowel disease from the Inflammatory Unit of the Virgin Macarena University Hospital will be randomized 1:1 to receive the study drug, Adalimumab biosimilar (AMGEVITA®) subcutaneous 40mg every 15 days or maintain the original drug (Humira®) 40 mg subcutaneous every 15 days. The dosage of the medication will be administrated according to the product's approved label by SmPC (Summary of Product's Characteristics)by technical file. Administration will be accepted every 7 days, if the patient after inclusion criteria is included with intensified dose.

Official Title
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Loss of Response of Adalimumab Biosimilar Compared With the Loss of Response of Adalimumab Original: Controlled, Randomized, Non-inferiority Open Study. ADA-SWITCH Study

Conditions
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Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Drug: Amgevita 40Mg Solution for Injection
* Drug: HUMIRA 40Mg Solution for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female over 18 years of age Be a Patient with a previous confirmed diagnosis of Crohn´s disease an Ulcerative Colitis Previous treated with original Adalimumab for at least 6 months with regular maintenance dose (40 mg every 15 days) and in clinical and biological remission. Patients under treatment with intensified Adalimumab (40mg every 7 days or 80mg every 7 days) to maintain clinical and biological remission for at least 6 months. Patients with oral mesalazine with a stable dose for more than 30 days. Patients with immunosuppressive therapy (methotrexate, azathioprine) with a minimum intake time> 60 days. Patients may be accepted with corticosteroids at the established doses: prednisone <20mg / dl, budesonide <9mg / dl. Patients who have a tuberculosis (TB) study (Mantoux / QuantiFERONTB test) updated in the last two year, with a negative result. Patient with serology hepatitis B and C, updated at the beginning of the treatment with Humira® Sign an informed consent document indicating that he/she understands the purpose of, and procedures required for, the study and are willing to participate in the study. Exclusion Criteria: Positive pregnancy test at the time of inclusion or during the follow-up period, as well as women who are breastfeeding Patients with uncontrolled comorbidities, active cancer, diabetes mellitus, severe cardiovascular disease, obstructive pulmonary disease, serious active infections. Patients with oral mesalazine initiated less than 30 days. Patients with immunosuppressive therapy (methotrexate, azathioprine) with a minimum intake time of <60 days. Patient with original Adalimumab who do not meet a minimum of 6 months of stable dose (40 mg every 7 or 15 days) Patient on corticosteroid therapy at doses: prednisone> 20mg / dl, budesonide = 9mg / dl, or with IV corticoids within 14 days prior screening date. Patients with mental disorders, alcohol / other substance abuse, or conditions that do not allow adherence to the study protocol. Patients with active TB Patients with defined Hepatitis B and C defined as: HBV: hepatitis B surface antigen (HbsAg) positive together with positive HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR). HCV: HCV ribonucleic acid (RNA) detectable in any patient with positive anti-HCV antibody (IgG)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: switch-cohort<br>Adalimumab biosimilar | Drug: Amgevita 40Mg Solution for Injection<br>* Adalimumab 40Mg Solution for Injection<br>* Other names: AMGEVITA;|
| Active Comparator: non-switchcohort<br>Adalimumab original | Drug: HUMIRA 40Mg Solution for Injection<br>* Adalimumab 40Mg Solution for Injection<br>* Other names: HUMIRA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to final follow-up in the response of the switch. | To assess if there is a change in the response of the switch (replacement) from Adalimumab original (Humira®) to Adalimumab biosimilar (Amgevita®) trhough the quantification of concomitant steroids needed or increment in dose or frequency of adalimumab biosimilar or urgent surgery indication | From date of randomization until the date of first documented change from baseline status in concomitant steroids needed or increment in dose or frequency of adalimumab biosimilar or urgent surgery indication ever came first, assessed up to 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the antibody formation rate. | Compare the antibody formation rate with Adalimumab(immunogenicity) after the switch. | 0, 3, 6, 9, 12, 13 months | 
| The score of the specific quality of life questionnaire | Compare the score of the specific quality of life questionnaire Short Inflammatory Bowel Disease Questionnaire (SIBDQ) in patients with inflammatory bowel disease before and after the switch.The minimum value is 1 and the maximum is 7, where higher scores means better outcome. | 0, 3, 6, 9, 12, 13 months | 
| The score of the Visual Analogue Scale (VAS) | Compare the score of the Visual Analogue Scale (VAS) of pain at the puncture site after the switch. The minimum value is 0 mm and the maximum value is 100 mm, where the higher score means a worse outcome. | 0, 3, 6, 9, 12, 13 months | 
| Maintenance of bioquimical remission trhough C-reactive protein | levels of C-reactive protein in blood (mg/L). | 0, 3, 6, 9, 12, 13 months | 
| Maintenance of bioquimical remission through Calprotectin values | levels of Calprotectin in blood (µg/g). | 0, 3, 6, 9, 12, 13 months | 
| Drug levels | Determination of drug levels in blood (µg/ml). | 0, 3, 6, 9, 12, 13 months | 
| Adverse Event | Proportion of patients who experience AE in each treatment group | 0, 3, 6, 9, 12, 13 months | 
| Hospital admission rate | Proportion of patients requiring hospital admissions related to a disease outbreak during follow-up. | 0, 3, 6, 9, 12, 13 months | 
| Surgery rate | Proportion of patients requiring surgery related to disease activity during follow-up. | 0, 3, 6, 9, 12, 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Loss of response, Switching, Adalimumab original, Adalimumab biosimilar