Application of N-of-1 Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

Official title: Application of the N-of-1 Trial Design in Rheumatoid Arthritis

Status Not yet recruiting

Clinical Trial Summary

The goal of this N-of-1 study is to learn about treatment for individual patients who have rheumatoid arthritis (RA,) for which many treatments are available. The treatments are different in how they work, the way they are given, side- effects, and cost. While treatment guidelines are available, finding the best treatment order of treatments is often based on physician choice. The main question this study aims to answer are:

• What are the effects of different treatments on RA symptoms and condition for each individual patient

• What is the effectiveness of different treatments across all patients enrolled in the N-of-1 study

Participants will be enrolled and randomized to a sequence of three U.S. Food and Drug Administration (FDA) approved RA medications: 1. adalimumab, 2. sarilumab, and 3. upadacitinib. Participants will be asked to complete questionnaires about their condition and quality of life weekly (either in clinic or remotely) and report their level of pain daily (remotely).

Clinical Trial Description

Rheumatoid arthritis (RA) is a chronic, slowly progressive condition for which numerous treatment options are available. The therapies vary in mechanism of action, mode of administration, side- effect (adverse event) profile, and cost. While consensus treatment guidelines are available, identifying an optimal treatment sequence is often based on clinician choice with treatment changes based on tolerability and short- term outcome. The N-of-1 trial will evaluate individual participant and aggregate data.

Individual participants will be enrolled and randomized to a sequence of three U.S. Food and Drug Administration (FDA)-approved therapeutic agents - adalimumab, sarilumab, upadacitinib- plus matching placebos to enable blinding of patients, clinicians, and study personnel.

The N-of-1- RA protocol describes patient allocation into a series of individual randomized comparisons. These treatment conditions are double-blind and randomized, with inclusion of matching parallel placebo treatments identical in appearance to the active medications:

• Patients with newly diagnosed rheumatoid arthritis following initial treatment with methotrexate (MTX). Prior to randomization, participants will be allocated to:

• MTX responder

• MTX non- responder

Eligible participants will either continue MTX or discontinue MTX, based on response to initial therapy and tolerance. Participants identified for subsequent biologic therapy will enter the blinded biologic therapy phase of the study; with MTX either continued or not continued. This phase consists of a sequence of 3 therapeutic intervention regimens, each lasting 12-weeks. Each treatment period includes matching parallel placebo treatments identical to the active medications in appearance to ensure blinding of patients, clinicians, and study personnel.

The treatment conditions are as follows:

A. Tumor Necrosis Factor (TNF) Inhibitor biologic: Adalimumab 40 mg subcutaneously every 2 weeks via subcutaneous injection with oral placebo once daily.

B. Non-TNF-Inhibitor biologic: Sarilumab 200 mg via subcutaneous injection every 2 weeks with oral placebo once daily.

C. Janus Kinase (JAK) Inhibitor: Upadacitinib 15 mg orally once daily with subcutaneous placebo injection every 2 weeks.

Primary Objective (individual N-of-1 trial): To generate randomized evidence about the effects of therapeutic agents on RA symptoms and disease activity to inform decision about best treatment at the end of the trial period for each participant.

Secondary Objective (aggregation of the series of N-of-1 trials): To evaluate the average relative effectiveness of therapeutic agents across all participants and explore heterogeneity of treatment effects.

For the aggregated series of N-of-1 trial, we will use the following hierarchy of endpoints.

• Primary Endpoint:

• DAS28 (CRP)

• Secondary Endpoints including:

• American College of Rheumatology 20% (ACR20), 50% (ACR50) and 70% (ACR70) response

• Routine Assessment of Patient Index Data (RAPID3) score based on participants' report of overall assessment of the disease, the level of pain, and the amount of physical disability ;

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

• NCT number: NCT06016517
• Study type: Observational
• Source: Tufts Medical Center
• Contact: Dorothy Dulko
• Phone: 6176365009
• Email: ddulko@tuftsmedicalcenter.org
• Status: Not yet recruiting
• Start date: July 1, 2024
• Completion date: July 1, 2025