Clinical trial NCT03784547: Real-world Data of Ocrelizumab in Multiple Sclerosis in LATAM
Official title: Real-world Patient Profile and Treatment Persistence of Ocrelizumab in Multiple Sclerosis: A Retrospective Analysis in Latin America
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis
Keywords: multiple sclerosis
Latin america
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
First posted: 2018-12-24
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients must meet the following inclusion criteria:

MS patients who received ocrelizumab to treat their disease

Brief summary: It has been almost 25 years since the publication of the pivotal trial results for the first disease-modifying therapy (DMT) for RRMS. Currently disease modifying therapies (DMTs) for MS approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA) include interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and ocrelizumab. Despite evidence about ocrelizumab exist in many patients from eurpe and North America, scarce real world evidence exists about epidemiolofcal aspects of patients that used ocrelizumab in Latin America.

The aim of this study is therefore to evaluate patient profiles and persistence to treatment during follow up in a retrospective study of patients who had been prescribed ocrelizumab for the treatment of MS in Latin America (LATAM). The investigators will include MS patients that received ocrelizumab in Latin America and describe epidemiological aspects and persistence to treatment during the last 12 months.

Detailed description: Multiple sclerosis is a chronic inflammatory disease of the CNS that leads to focal plaques of primary demyelination and diffuse neurodegeneration in the grey and white matter of the brain and spinal cord 1. In most patients, the disease starts with a relapsing-remitting course (RRMS), which is followed several years by a secondary progressive phase (SPMS). Patients with primary progressive disease (PPMS) miss the relapsing and remitting stage and start with uninterrupted progression from disease onset 1-3.

It has been almost 25 years since the publication of the pivotal trial results for the first disease-modifying therapy (DMT) for RRMS 4. Currently disease modifying therapies (DMTs) for MS approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA) include interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and ocrelizumab 5-7.

Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS 8. A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate (P \< 0.001 pooled), disability progression at 12 weeks ( P \< 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P \< 0.001) 8. Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P \< 0.001) 8. As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection8. Despite much information exists about efficacy and safety of ocrelizumab in phase III clinical trials, scarce evidence exists regarding real world patients profile and safety.

The aim of this study is therefore to evaluate patient profiles and persistence to treatment during follow up in a retrospective study of patients who had been prescribed ocrelizumab for the treatment of MS in Latin America (LATAM)

Methods

Verbal/written consent from patient only if any site's Ethic Committee requests it.

Centers involved in the study will be from Mexico, Chile, Argentina Number of centers \& patients Two centers in Argentina, two centers in Chile, and two centers in Mexico. Total: 6 centers and Approx 80 patients.

Study overview Patients that accept to participate and fulfill all inclusion criteria and none exclusion criteria will be included. All information will be extracted from the medical charts Data Source Information related to the study population will be extracted from the patient medical chart review (secondary data use) and will cover a period up to protocol regulatory approval. Patient identity will be coded and anonymized in the study data base so only each investigator will know the identity of each patient. Local legislation regarding patient data protection will be followed strictly in this study. All study data will be entered in a predefined electronic Case Report Form (CRF).

This is an NIS involving the use of secondary data and the reporting of adverse reactions in the form of ICSRs is not required. The study will not extract safety information.

Storage and data analysis

Once the patient is identified and consented to participate (if needed based on local regulatory aspects), data from patient's chart will be transferred into the specifically designed platform. The platform on which variables will be transferred, will be on a web platform with restricted access by user and password specific to each researcher. When sharing the data, it will be anonymized and only data related to the demographics and clinic will be accessible, and patient data such as name, surname and ID will not be visible to analysts if it is loaded.

Data protection

The regulatory requirements and protection of personal data must be completed according to the regulations corresponding to each participant.

Each researcher in the study should explain in detail to each potential participant the record consists. Every patient who wishes to participate in the project must consent, according to each regulation, authorizing that their information, codified and anonymized, be shared with other records for analysis and communication.

An institutional ethics committee must approve the registration or declare that it is exempt from the need for approval as well as its informed consent (IC).

The data will be uploaded by the physician of each participating center. The different variables will be obtained from the daily clinical practice of each professional.

Patient Confidentiality As mentioned in the previous point, the patient's name, address, date of birth, ID or telephone number will only be left in the personal registry and at the moment of sharing the registration to the central registry will not be entered. The records will then be identified by a unique code generated by the initials of the IP and the registration number of that patient.

Each registry should include baseline clinical and demographic data as well as the study project data.

At all times, the protection of the patient's identity and data will be observed in accordance with the legal regulations in force national law of protection of personal data 25.326 (Habeas Data), in accordance with the international legislation on registration of diseases and protection of personal data and private, according to the 18th World Medical Assembly of Helsinki (1964) when applicable. The right to non-participation in the study will be respected always without this implying in any case any type of discrimination, differential treatment or mistreatment towards the patient.

This is a retrospective observational study, which does not plan any type of intervention or differential treatment in patients included or excluded.

Statistical analysis plan This is descriptive study and sample size is not based on statistical considerations. A descriptive analysis is the main objective of the study regarding demographic, clinical aspects, disease activity and persistence to treatment of patients that received ocrelizumab to treat their MS disease.

Eligibility criteria: Inclusion Criteria:

- multiple sclerosis patients that received ocrelizumab

Exclusion Criteria:

-

Primary outcomes:
measure: Proportion of patients discontinuing the treatment with ocrelizumab in the last 12 months after inclusion
timeFrame: 12 months
measure: Multiple sclerosis phenotype
timeFrame: 12 months
Secondary outcomes:
measure: Gender
timeFrame: 12 months
measure: Age at study entry
timeFrame: 12 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Juan Ignacio Rojas
city: Buenos Aires
country: Argentina
facility: Juan Ignacio Rojas
city: Buenos Aires
country: Argentina
facility: Juan Ignacio Rojas
city: Buenos Aires
country: Argentina
facility: Edgard Carnero
Study officials:
References: