Loss of Response of Adalimumab Biosimilar vs Adalimumab Original, in Inflammatory Bowel Disease. (ADA-SWITCH)

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

Loss of response of the Adalimumab biosimilar compared with the original drug.

Study Overview

• Status: Terminated
• Conditions: Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Drug: Amgevita 40Mg Solution for Injection; Drug: HUMIRA 40Mg Solution for Injection

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: switch-cohort; Adalimumab biosimilar	Drug: Amgevita 40Mg Solution for Injection; Adalimumab 40Mg Solution for Injection; Other Names: AMGEVITA
ACTIVE_COMPARATOR: non-switchcohort; Adalimumab original	Drug: HUMIRA 40Mg Solution for Injection; Adalimumab 40Mg Solution for Injection; Other Names: HUMIRA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Investigators: Principal Investigator: Federico Argüelles Arias, Md PhD, Universitary Hospital Virgen Macarena

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 10, 2019
• Primary Completion (ACTUAL): June 8, 2020
• Study Completion (ACTUAL): June 8, 2020

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (ACTUAL): October 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Switching; Loss of response; Adalimumab original; Adalimumab biosimilar
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab; Pharmaceutical Solutions
• Other Study ID Numbers: AMGEVITA-HVM2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No