Rheumatoid Arthritis
Conditions
Keywords
rheumatoid arthritis, RA, noninvasive, autoimmune, cholinergic anti-inflammatory pathway, neuroimmune modulation, spleen
Brief summary
This two-stage, multicenter clinical trial is designed to evaluate the feasibility, safety, and preliminary efficacy of splenic ultrasound stimulation to activate immune-neuromodulation (SUSTAIN) in patients with rheumatoid arthritis (RA) and at least moderate disease activity. 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.
Detailed description
Stage 1 is an open-label pilot study of 6-10 participants. To maintain a seropositive-enriched cohort, enrollment of seronegative participants (those with RF ≤14 IU/mL and Anti-CCP \<20 U/mL) is capped at 3 participants in Stage 1. All participants will receive daily active SUSTAIN therapy for 8 weeks. The initial active ultrasound parameter set (Experimental Treatment 1) will be based on the best available evidence at the start of the trial. If interim review of early efficacy data from the first 3-5 participants, specifically, the magnitude and direction of change in DAS28-CRP from Baseline to Week 4, suggests that a second parameter set may be warranted, the Sponsor may elect to enroll an additional 3-5 participants to receive a second active ultrasound parameter set (Experimental Treatment 2). This decision will be made by the Sponsor prior to enrollment of the first participant assigned to Experimental Treatment 2 and will be documented in a protocol decision memo. If the Sponsor determines that Experimental Treatment 1 demonstrates sufficient early signal, Stage 1 will be completed using a single parameter set. The primary objective of Stage 1 is to assess feasibility, defined as ≥70% adherence to scheduled treatment sessions, 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 double-blind, randomized, sham-controlled study enrolling 30-40 participants, randomized 1:1 to receive daily active or sham SUSTAIN therapy for 8 weeks. Selection of the Stage 2 active treatment ultrasound parameter set will be based on the safety profile and magnitude/direction of the DAS28-CRP change from Baseline to Week 4 of the two experimental treatments. Enrollment of seronegative participants is capped at 10 in Stage 2, such that at least 75% of enrolled participants are seropositive. Randomization is stratified by serostatus to maintain balance across arms. This stage is designed to further characterize safety and adherence in a larger cohort, and to estimate treatment effect size using clinical and biomarker-based secondary endpoints. 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 an open-label pilot of 6-10 participants divided into two groups (experimental treatment 1 or experimental treatment 2). Stage 2 is randomized, double-blind, sham-controlled trial of 30-40 participants with 2 arms, active treatment and sham, that are allocated 1:1.
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 * At least moderate disease activity, defined as ≥4 tender joints (28-joint count) and ≥4 swollen joints (28-joint count) and a DAS28-CRP \>3.2 at the baseline visit * hsCRP \> 0.3 mg/dL at the last qualifying visit, baseline or retest * If on background DMARD therapy, must be on stable dose (see
Exclusion criteria
) * Able and willing to comply with all study-related procedures, including daily treatment sessions in the study vehicle, research site visits, and assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Adherence to Therapy | 8 weeks | Proportion of patients adherent to treatment, defined by completing ≥70% of the 56 scheduled ultrasound treatments |
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. |
| Change in high sensitivity CRP (hsCRP) | Weeks 2, 4, 6, and 8 | The primary endpoint is the change in hsCRP from baseline to weeks 2, 4, 6 and 8. |
Countries
United States
Contacts
CONTACTAlexander Sackeim, MD
CONTACTUsman Asaf
Outcome results
None listed