Clinical trial NCT05636709: National GMA Post-market Clinical Follow-up Study (GRACE)
Official title: National Post-market Clinical Follow-up Study to Evaluate in Real-world Practice the Efficacy and Safety of Granulocytoapheresis and Its Impact on Quality of Life in Patients With Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Crohn Disease
Ulcerative Colitis
Lead sponsor: Adacyte Therapeutics SL
Sponsor class: INDUSTRY
First posted: 2022-12-05
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with Ulcerosis Colitis or Crohn disease from about 30 centres in Spain in whom the physician in charge of treatment decides to start treatment with GMA and independently of their inclusion in the study.

Brief summary: Inflammatory bowel disease (IBD) encompasses several chronic diseases of which ulcerative colitis (UC) and Crohn's disease (CD) are the most representative. IBD is characterised by the presence of an inflammatory process that affects different segments of the digestive tract and has a chronic and relapsing course with flares of activity.

Inflammatory activity in IBD is associated with an increase in peripheral blood activated granulocytes and monocyte-macrophages and intestinal infiltration by these inflammatory cells, which are largely responsible for tissue damage. In recent years, observational, prospective studies and meta-analyses of these studies have contributed to consider granulocytapheresis (GMA) as an effective and safe alternative in the treatment of UC.

This apheresis technique is based on recirculation of the patient's blood through a circuit with cellulose acetate spheres that perform a selective elimination of granulocytes and monocyte-macrophages leading to a reduction in pro-inflammatory cytokines and adhesion molecule expression, and an increase in anti-inflammatory mediators. These events in the GMA column are followed by other immunological changes, most notably a decrease in CD10+ (activated) neutrophils, leading to a compensation from the bone marrow of a CD10- (immature) neutrophil population.

GMA can be considered as a therapeutic alternative in corticodependent IBD, especially in UC. In addition, it can reduce or limit the need for corticosteroids, so another possible application is as a "bridge" treatment in patients starting treatment with thiopurine immunomodulators. A beneficial effect can also be obtained by combining apheresis with biological treatments, especially after a partial response or loss of response to these treatments. Finally, some extraintestinal manifestations associated with IBD may also benefit from its use.

The GRACE study is proposed for the evaluation of the efficacy of GMA with Adacolumn® under real conditions of use and according to the indications described in the instructions for use of the medical device.

Detailed description: It is planned to enrol a minimum of 350 patients from approximately 30 sites. To avoid screening biases, the patients to be included per site will be selected consecutively from among those who meet the eligibility criteria to participate in the study.

A national, multicentre, noninterventional post-market clinical follow-up (PMCF) study with an estimated follow-up period of 12 months after completion of GMA therapy to evaluate the efficacy of Adacolumn® GMA in actual conditions of use, as specified in the product instructions for use, in adult patients diagnosed with UC or CD. Approximately 350 patients from about 30 centres in Spain are planned to be included.

The standard regimen according to product instructions for use is one session per week for 5 consecutive weeks, although in specific cases continuous regimens have been established for maintenance (one or two sessions per month) or others for induction (two sessions per week). The use of a higher number of sessions seems to increase efficacy from 40% with 5 sessions to 80% with 10 in the more refractory cases and may achieve a greater reduction in steroid use. In Europe, where GMA is used in different scenarios, it is routinely being used in 7 to 10 sessions.

The study will consist of a maximum of 4 visits: a baseline visit, which will coincide with patient inclusion in the study, and 3 follow-up visits at 4 (±2 weeks) (month 1), 24 (±2 weeks) (month 6) and 48 (±2 weeks) (month 12) weeks after the last session of induction apheresis.

All visits scheduled during the study will coincide with any of the patient visits made as part of routine clinical follow-up, without interfering with the investigator's clinical duties. Note: In the event that a patient discontinues Adacolumn® GMA, the reasons for discontinuation of the procedure will be recorded and the change in treatment for IBD, if any.

Once the patient has been adequately informed, his/her eligibility has been confirmed and he/she has signed the informed consent (IC), the investigator will start data collection in an appropriate and precise manner. Therefore, no diagnostic or therapeutic intervention outside of routine clinical practice will be applied. To ensure the noninterventional nature of the study, the data will be collected provided they are available in the patient's medical record or can be collected during patient visits to his/her physician as part of actual clinical care (as in the case of questionnaires used as source documents).

Adacolumn® is a medical device intended for modifying the biological or chemical composition of the blood (class IIb), according to Regulation (UE) 2017/745 on Medical Devices, manufactured by Japan Immnunoresearch Laboratories, JIMRO (Takasaki, Japan). It consists of a 335 ml column formed by cellulose acetate beads of 2 mm in diameter bathed in saline, where granulocytes (65%), monocytes (55%), and only 2% of lymphocytes are selectively adsorbed.

Adacolumn® is indicated for induction of remission in patients with IBD (active UC and CD), for suppression of subjective and objective symptoms in patients with rheumatoid arthritis in the inflammatory stage whose symptoms might be resistant to standard drug therapy, for treatment of patients with ocular Behcet disease and for treatment of patients with systemic lupus erythematosus.

In this study, the intended use of Adacolumn® is for application of GMA in patients diagnosed with IBD, both UC and CD

Eligibility criteria: Inclusion Criteria:

1. ≥18 years.
2. Established diagnosis of UC or CD according to ECCO criteria.
3. Patients in whom the physician in charge of treatment decides to start treatment with GMA and independently of their inclusion in the study.
4. Patients who understand and voluntarily sign informed consent.

Exclusion Criteria:

1. Patient with any medical or psychological disorder that, in the investigator's opinion, may interfere with the patient's ability to comply with the study procedures.
2. Patient who is participating in a clinical trial.

NOTE: If the physician knows or suspects that the patient is unable to understand the implications of his/her participation in the study, the patient should not enter without the signature of his/her legal representative

Primary outcomes:
measure: Proportion of patients achieving steroid-free clinical remission at 6 months after completion of GMA therapy
timeFrame: 6 months
Secondary outcomes:
measure: Define the regimens used for GMA in actual clinical practice.
timeFrame: 12 months
measure: Early clinical remission rate
timeFrame: 1 month
measure: 6- and 12-month remission rates completion of GMA therapy
timeFrame: 6 and 12-month
measure: Sustained clinical remission rate
timeFrame: 12 months
measure: 6- and 12-month clinical response rates
timeFrame: 6 and 12-month
measure: Rate of patients receiving GMA as maintenance and its efficacy
timeFrame: 12 months
measure: Rate of patients requiring steroids and mean dose during follow-up
timeFrame: 12 months
measure: Changes in faecal calprotectin and C-reactive protein (CRP) biomarkers during treatment
timeFrame: 12 months
measure: Rate of treatment-related adverse events (AEs) and seriousness
timeFrame: 6 months
measure: Change in patients' quality of life
timeFrame: 6 months
measure: Number of patients requiring surgery
timeFrame: 6 months
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: H. Germans Trias i Pujol
state: Barcelona
city: Galdakao
country: Spain
facility: H. Galdakao
state: Bizkaia
city: Castelló de la Plana
country: Spain
facility: H. General de Castellón
state: Castellón
city: San Sebastián
country: Spain
facility: H. Donostia
state: Gipuzkoa
city: Santiago De Compostela
country: Spain
facility: H. Santiago
state: La Coruña
city: Logroño
country: Spain
facility: H. San Pedro
state: La Rioja
city: Las Palmas De Gran Canaria
country: Spain
facility: H. Dr. Negrín
state: Las Palmas de Gran Canarias
city: Marbella
country: Spain
facility: H. Costa del Sol
state: Málaga
city: Pamplona
country: Spain
facility: H. Navarra
state: Navarra
city: Vigo
country: Spain
facility: H. Álvaro Cunqueiro
state: Pontevedra
city: La Laguna
country: Spain
facility: H. Univ. de Canarias
state: Santa Cruz de Tenerife
city: Albacete
country: Spain
facility: H. Albacete
city: Alicante
country: Spain
facility: H. General de Alicante
city: Barcelona
country: Spain
facility: H. Vall d´hebron
city: Cádiz
country: Spain
facility: H. Puerta del Mar
city: Córdoba
country: Spain
facility: H. Reina Sofía
city: Granada
country: Spain
facility: H. Virgen de las Nieves
city: Guadalajara
country: Spain
facility: H. Guadalajara
city: Huesca
country: Spain
facility: H. San Jorge
city: Madrid
country: Spain
facility: H. 12 de octubre
city: Madrid
country: Spain
facility: H. La Paz
city: Palencia
country: Spain
facility: H. Río Carrión
city: Palma De Mallorca
country: Spain
facility: H. Son Espases
city: Palma de Mallorca
country: Spain
facility: H. Son Llatzer
city: Santa Cruz De Tenerife
country: Spain
facility: H. Ntra. Sra. de Candelaria
city: Sevilla
country: Spain
facility: H. Virgen del Rocío
city: Valencia
country: Spain
facility: H. Clínico Univ. de Valencia
city: Valencia
country: Spain
facility: H. General de Valencia
city: Valencia
country: Spain
facility: H. La Fe
city: Zamora
country: Spain
facility: H. Virgen de la Concha
Study officials:
affiliation: H. Galdakao
name: Jose Luis Cabriada
role: STUDY_CHAIR
affiliation: H. Galdakao
name: Iago Rodríguez
role: STUDY_CHAIR
affiliation: H. Son Espases
name: Daniel Ginard
role: STUDY_CHAIR
References: