Clinical trial NCT04131322: Loss of Response of Adalimumab Biosimilar vs Adalimumab Original, in Inflammatory Bowel Disease.
Official title: Loss of Response of Adalimumab Biosimilar Compared With the Loss of Response of Adalimumab Original: Controlled, Randomized, Non-inferiority Open Study. "ADA-SWITCH Study"
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Crohn Disease
Ulcerative Colitis
Keywords: Loss of response
Switching
Adalimumab original
Adalimumab biosimilar
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2019-10-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Loss of response of the Adalimumab biosimilar compared with the original drug.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change from baseline to final follow-up in the response of the switch.
timeFrame: 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 outcomes:
measure: Compare the antibody formation rate.
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: The score of the specific quality of life questionnaire
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: The score of the Visual Analogue Scale (VAS)
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Maintenance of bioquimical remission trhough C-reactive protein
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Maintenance of bioquimical remission through Calprotectin values
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Drug levels
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Adverse Event
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Hospital admission rate
timeFrame: 0, 3, 6, 9, 12, 13 months
measure: Surgery rate
timeFrame: 0, 3, 6, 9, 12, 13 months
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Universitary Hospital Virgen Macarena
name: Federico Argüelles Arias, Md PhD
role: PRINCIPAL_INVESTIGATOR
References: