Rheumatoid Arthritis (RA
Conditions
Keywords
rheumatoid arthritis, RA, noninvasive, autoimmune
Brief summary
This two-stage, multicenter clinical trial is designed to evaluate the feasibility, safety, and preliminary efficacy of at-home ultrasound stimulation to activate immune-neuromodulation in patients with rheumatoid arthritis (RA) and at least moderate disease activity. The study will enroll up to 40 participants at up to 6 sites across 2 stages. The findings from this trial will directly inform the design and power calculations for a future pivotal trial by identifying an appropriate effect size and confirming protocol feasibility and safety for a daily home-use therapy.
Detailed description
Stage 1 is an open-label pilot study of 5-8 participants receiving active daily ultrasound stimulation for 8 weeks. The primary objective is to assess feasibility and safety, defined by the absence of device-related serious adverse events (SAEs) or Grade ≥2 adverse events (AEs) requiring medical intervention per CTCAE criteria. Data from Stage 1 will be used to refine trial procedures and confirm readiness for Stage 2. Stage 2 consists of a randomized double-blind, sham-controlled study enrolling up to 30 participants, allocated 2:1 to receive active or sham daily ultrasound stimulation for 8 weeks. This stage is designed to estimate the treatment effect size, using clinical and biomarker-based endpoints, and to collect safety and adherence data on a larger cohort. All participants will be followed through Week 12 to assess post-treatment safety and durability of clinical and immunologic effects.
Interventions
DEVICEActive treatment
Daily active ultrasound stimulation
DEVICESham (No Treatment)
Daily sham ultrasound stimulation
Sponsors
Surf Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
In addition the laboratory personnel analyzing the blood samples, and the statistician analyzing the trial data will be blinded to treatment group.
Intervention model description
Stage 1 is a single group and open-label. Stage 2 is randomized, double-blind, sham-controlled with 2 treatment arms, active and sham, that are allocated 2:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old * Diagnosis of rheumatoid arthritis as defined by ACR/EULAR 2010 classification criteria * A positive test result for Rheumatoid Factor (RF) \> 14 IU/mL and/or Anti-Citrullinated Protein Antibodies (Anti-CCP) ≥ 20 U/mL * At least moderate disease activity, defined as DAS28-CRP \> 3.8 and at least 4/28 tender and 4/28 swollen joints at the screening and baseline visits * High sensitivity CRP (hsCRP) ≥ 10 mg/L at the screening and baseline visits * On stable dose of background DMARD therapy (see
Exclusion criteria
) * Able and willing to comply with all study-related procedures, including at-home device use, daily treatment, scheduled visits, and assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in high sensitivity CRP (hsCRP) | 8 weeks | The primary endpoint is the change in hsCRP from baseline to weeks 2, 4, 6 and 8. The baseline value will be calculated as the average of the screening and baseline visits, both of which must be ≥ 10 mg/L. |
| Incidence of Adverse Events | 12 weeks | All adverse events (AEs) regardless of treatment group that occur over the 12 week enrollment period will be coded and summarized by frequency, severity, and relatedness using the latest MedDRA version (v28.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American College of Rheumatology (ACR) 20, 50 and 70 response rates | Week 8 | Difference between treatment and control groups in the proportion of subjects who achieve at least 20%, 50%, and 70% improvement from baseline to Week 8 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL). |
| Change in Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP). | Week 8 | Defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline to week 8. |
| Change in Heath Assessment Questionnaire Disability Index (HAQ-DI) | Week 8 | Haq-DI assesses physical function through eight daily activity domains (scale 0=no difficulty to 3=unable to do). Change from baseline to week 8 based on the MCID of -0.22. |
| Change in Clinical Disease Activity Index (CDAI) score for Rheumatoid Arthritis | Week 8 | The CDAI assesses disease activity by summing tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), and physician global assessment (EGA). CDAI will be assessed from Baseline to Week 8. |
| Change in Simplified Disease Activity Index (SDAI) for Rheumatoid Arthritis (RA) | Week 8 | The SDAI is a measure of disease activity that includes all the 4 components of the CDAI, plus CRP. SDAI will be assessed from baseline to Week 8. |
Countries
United States
Outcome results
None listed