Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, Vagus nerve, vagus nerve stimulating device, drug refractory, permanent implantable, implant
Brief summary
The RESET-RA study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis who have had an inadequate response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically placed under general anesthesia on the vagus nerve through a small incision on the left side of the neck (implant procedure). The study will enroll up to 250 subjects at up to 45 sites. All eligible subjects will undergo the implant procedure. Half of the subjects will receive active stimulation (treatment) and the other half will receive non-active stimulation (control). After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.
Detailed description
The RESET-RA study is an operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter pivotal study enrolling up to 250 subjects at up to 45 study centers across the U.S. The study will assess the safety and efficacy of the SetPoint System (study device) for the treatment of adult patients with active, moderate to severe rheumatoid arthritis (RA) who have had an inadequate response, loss of response or intolerance to biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). The study device contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). The implant delivers a small amount of electricity (stimulation) to the nerve. All eligible subjects will undergo the surgery under general anesthesia. Half of the subjects will receive active stimulation (the treatment group) and the other half will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 12 weeks. After completing primary endpoint assessments at Week 12, there will be a one-way crossover of control subjects to active stimulation and a 252-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained until the last enrolled and randomized subject in Stage 2 completes Week 12 assessments, and the study database is locked.
Interventions
PROCEDUREImplant Procedure
The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.
All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent
DEVICEActive stimulation
Active stimulation for 1 min once per day
DEVICENon-active stimulation
Non-active stimulation for 1 min once per day
Sponsors
SetPoint Medical Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All subjects, investigators, joint evaluators and study staff will be blinded. Blinding of subjects, joint evaluators and investigators will be assessed at Weeks 4 and 12.
Intervention model description
An operationally seamless, 2-stage, randomized, double-blind, sham-controlled, multicenter study. Subjects will be assigned randomly in a 1:1 ratio into either a treatment or control group. Subjects assigned to the treatment group will receive active stimulation for 1 min once per day, and those assigned to the control group will receive non-active stimulation for 1 min once per day.
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 22-75 years of age at screening * Active moderate or severe RA, defined as at least 4/28 tender and 4/28 swollen joints * Demonstrated an inadequate response, loss of response, or intolerance to 1 or more approved for rheumatoid arthritis biologic or targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), including Janus kinase inhibitors (JAKi) * Receiving treatment with at least 1 conventional synthetic DMARD for at least 12 weeks and on a continuous non-changing dose and route of administration for at least 4 weeks prior to Screening and able to continue the same stable dose through Week 12
Exclusion criteria
* Untreated or poorly controlled psychiatric illness or history of substance abuse * Significant immunodeficiency due to underlying illness * History of stroke or transient ischemic attack, or diagnosis of cerebrovascular fibromuscular dysplasia * Clinically significant cardiovascular disease * Neurological syndromes, including multiple sclerosis, Alzheimer's disease, or Parkinson's disease * Uncontrolled fibromyalgia * History of left or right carotid surgery * History of unilateral or bilateral vagotomy, partial or complete splenectomy * Recurrent vasovagal syncope episodes * Current, regular use of tobacco products * Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the American College of Rheumatology (ACR) 20 Response | Week 12 | Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR) | Week 12 | The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) good or moderate response as 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). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 A subject is considered having a moderate treatment response if: * DAS28-CRP score improvement from baseline to Week 12 is \> 0.6 and ≤ 1.2, and the DAS28-CRP score at Week 12 is ≤ 5.1; or * DAS28-CRP score improvement from baseline to Week 12 is \> 1.2, and the DAS28-CRP score at Week 12 is \> 3.2. A subject is considered having a good treatment response if: • DAS28-CRP score improvement from baseline to Week 12 is \> 1.2 and the DAS28-CRP score at Week 12 is ≤ 3.2 |
| DAS28-CRP Response (MCID -1.2) at Week 12 | Week 12 | The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) response is based on the minimal clinically important difference (MCID) of -1.2 from baseline. DAS28-CRP is 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). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 |
| Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22) | Week 12 | HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability |
| ACR20 Response at Week 12 From Day 0 | Week 12 | Response is defined as achieving at least 20% improvement from Day 0 to Week 12 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=worse), 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJohn Tesser, MD
Arizona Arthritis and Rheumatology Research, P.C.
PRINCIPAL_INVESTIGATORMark Richardson, MD PhD
Massachusetts General Hospital
Participant flow
Pre-assignment details
In total, 405 subjects were consented, and 162 subjects were screen failures. Of the 243 subjects meeting eligibility, 1 subject did not complete the implant procedure per Sponsor decision; the remaining 242 subjects were implanted and subsequently randomly assigned to either treatment with active stimulation (n=122) or control with sham, non-active stimulation (n=120).
Participants by arm
| Arm | Count |
|---|---|
| Treatment Active stimulation for 1 min once per day
Implant Procedure: The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.
Conventional Synthetic Disease-Modifying Antirheumatic Drug (DMARD): All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent
Active stimulation: Active stimulation for 1 minute once per day | 122 |
| Control Non-active stimulation for 1 min once per day
Implant Procedure: The SetPoint System (study device) contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). All eligible subjects will undergo the surgery under general anesthesia in outpatient settings.
Conventional Synthetic DMARD: All subjects will continue to take at least one type of conventional synthetic DMARD at the same stable dose as for 4 weeks prior to consent
Non-active stimulation: Non-active stimulation for 1 minute once per day | 120 |
| Total | 242 |
Baseline characteristics
| Characteristic | Control | Treatment | Total |
|---|---|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 10.49 | 55.8 years STANDARD_DEVIATION 10.28 | 55.7 years STANDARD_DEVIATION 10.36 |
| Anti-Citrullinated Protein Antibodies (ACPA) Missing | 0 Participants | 4 Participants | 4 Participants |
| Anti-Citrullinated Protein Antibodies (ACPA) Negative | 61 Participants | 57 Participants | 118 Participants |
| Anti-Citrullinated Protein Antibodies (ACPA) Positive | 59 Participants | 61 Participants | 120 Participants |
| Body Mass Index | 29.8 kg/m2 STANDARD_DEVIATION 6.71 | 30.7 kg/m2 STANDARD_DEVIATION 7.25 | 30.3 kg/m2 STANDARD_DEVIATION 6.98 |
| Clinical Disease Activity Index (CDAI) score | 38.2 score on a scale STANDARD_DEVIATION 12.75 | 36.1 score on a scale STANDARD_DEVIATION 12.6 | 37.1 score on a scale STANDARD_DEVIATION 12.69 |
| Disease Activity Score-28 with C-reactive protein (DAS28-CRP) score | 5.4 score on a scale STANDARD_DEVIATION 0.96 | 5.3 score on a scale STANDARD_DEVIATION 0.91 | 5.3 score on a scale STANDARD_DEVIATION 0.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 23 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 98 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Evaluator's Global Assessment (0-10) | 6.7 score on a scale STANDARD_DEVIATION 1.72 | 6.3 score on a scale STANDARD_DEVIATION 1.88 | 6.5 score on a scale STANDARD_DEVIATION 1.8 |
| HAQ-DI Score | 1.3 score on a scale STANDARD_DEVIATION 0.61 | 1.4 score on a scale STANDARD_DEVIATION 0.59 | 1.4 score on a scale STANDARD_DEVIATION 0.6 |
| hsCRP | 8.01 mg/L STANDARD_DEVIATION 12.762 | 8.41 mg/L STANDARD_DEVIATION 12.338 | 8.21 mg/L STANDARD_DEVIATION 12.526 |
| Number of prior b/tsDMARDs 1 | 42 Participants | 52 Participants | 94 Participants |
| Number of prior b/tsDMARDs 10+ | 1 Participants | 2 Participants | 3 Participants |
| Number of prior b/tsDMARDs 2 | 28 Participants | 25 Participants | 53 Participants |
| Number of prior b/tsDMARDs 3 | 16 Participants | 15 Participants | 31 Participants |
| Number of prior b/tsDMARDs 4 | 15 Participants | 15 Participants | 30 Participants |
| Number of prior b/tsDMARDs 5 | 8 Participants | 7 Participants | 15 Participants |
| Number of prior b/tsDMARDs 6 | 5 Participants | 2 Participants | 7 Participants |
| Number of prior b/tsDMARDs 7 | 4 Participants | 2 Participants | 6 Participants |
| Number of prior b/tsDMARDs 8 | 1 Participants | 2 Participants | 3 Participants |
| Number of prior b/tsDMARDs 9 | 0 Participants | 0 Participants | 0 Participants |
| Pain (0-10) | 5.7 score on a scale STANDARD_DEVIATION 2.23 | 5.5 score on a scale STANDARD_DEVIATION 2 | 5.6 score on a scale STANDARD_DEVIATION 2.12 |
| Prior b/tsDMARDs | 2.7 number of b/tsDMARDs STANDARD_DEVIATION 1.87 | 2.5 number of b/tsDMARDs STANDARD_DEVIATION 1.98 | 2.6 number of b/tsDMARDs STANDARD_DEVIATION 1.92 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 10 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 93 Participants | 102 Participants | 195 Participants |
| Region of Enrollment United States | 120 participants | 122 participants | 242 participants |
| Rheumatoid arthritis (RA) duration | 11.8 years STANDARD_DEVIATION 10.45 | 13.0 years STANDARD_DEVIATION 10.59 | 12.4 years STANDARD_DEVIATION 10.52 |
| Rheumatoid Factor (RF) Negative | 64 Participants | 73 Participants | 137 Participants |
| Rheumatoid Factor (RF) Positive | 56 Participants | 49 Participants | 105 Participants |
| Serology Missing | 0 Participants | 4 Participants | 4 Participants |
| Serology Negative | 54 Participants | 56 Participants | 110 Participants |
| Serology Positive | 66 Participants | 62 Participants | 128 Participants |
| Sex: Female, Male Female | 110 Participants | 98 Participants | 208 Participants |
| Sex: Female, Male Male | 10 Participants | 24 Participants | 34 Participants |
| Subject's Global Assessment (0-10) | 6.0 score on a scale STANDARD_DEVIATION 2.25 | 6.2 score on a scale STANDARD_DEVIATION 2.07 | 6.1 score on a scale STANDARD_DEVIATION 2.16 |
| Swollen Joint Count (out of 28 joints) | 10.5 number of joints STANDARD_DEVIATION 4.98 | 9.6 number of joints STANDARD_DEVIATION 5.46 | 10.0 number of joints STANDARD_DEVIATION 5.23 |
| Tender Joint Count (out of 28 joints) | 15.0 number of joints STANDARD_DEVIATION 7.26 | 14.1 number of joints STANDARD_DEVIATION 6.94 | 14.6 number of joints STANDARD_DEVIATION 7.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 122 | 0 / 120 |
| other Total, other adverse events | 74 / 122 | 79 / 120 |
| serious Total, serious adverse events | 22 / 122 | 29 / 120 |
Outcome results
Primary
the American College of Rheumatology (ACR) 20 Response
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response | 43 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response | 29 Participants |
p-value: 0.020995% CI: [0.6, 23.1]Cochran-Mantel-Haenszel
Secondary
ACR20 Response at Week 12 From Day 0
Response is defined as achieving at least 20% improvement from Day 0 to Week 12 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=worse), 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).
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | ACR20 Response at Week 12 From Day 0 | 38 Participants |
| Control | ACR20 Response at Week 12 From Day 0 | 27 Participants |
p-value: 0.079795% CI: [-3.1, 19]Cochran-Mantel-Haenszel
Secondary
DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR)
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) good or moderate response as 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). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 A subject is considered having a moderate treatment response if: * DAS28-CRP score improvement from baseline to Week 12 is \> 0.6 and ≤ 1.2, and the DAS28-CRP score at Week 12 is ≤ 5.1; or * DAS28-CRP score improvement from baseline to Week 12 is \> 1.2, and the DAS28-CRP score at Week 12 is \> 3.2. A subject is considered having a good treatment response if: • DAS28-CRP score improvement from baseline to Week 12 is \> 1.2 and the DAS28-CRP score at Week 12 is ≤ 3.2
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR) | 74 Participants |
| Control | DAS28-CRP Good or Moderate Response as Defined by European League Against Rheumatism (EULAR) | 50 Participants |
p-value: 0.004895% CI: [7.3, 31.7]Cochran-Mantel-Haenszel
Secondary
DAS28-CRP Response (MCID -1.2) at Week 12
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) response is based on the minimal clinically important difference (MCID) of -1.2 from baseline. DAS28-CRP is 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). A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Response (MCID -1.2) at Week 12 | 55 Participants |
| Control | DAS28-CRP Response (MCID -1.2) at Week 12 | 39 Participants |
p-value: 0.052895% CI: [1.1, 25.3]Cochran-Mantel-Haenszel
Secondary
Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22)
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22) | 56 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22) | 44 Participants |
p-value: 0.079795% CI: [-3.3, 21.4]Cochran-Mantel-Haenszel
Other Pre-specified
Bone Erosion Progression, All Completers
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows: * Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24. * Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250. * Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75. * CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100. The proportion of bone erosion progressors is the % subjects with an increase of \> 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of \> 0.5 represents disease progression.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Bone Erosion Progression, All Completers | 18 Participants |
| Control | Bone Erosion Progression, All Completers | 21 Participants |
p-value: 0.247695% CI: [-14.4, 7]Cochran-Mantel-Haenszel
Other Pre-specified
Bone Erosion Progression, All Completers That Previously Only Failed 1 b/tsDMARD
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows: * Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24. * Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250. * Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75. * CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100. The proportion of bone erosion progressors is the % subjects with an increase of \> 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of \> 0.5 represents disease progression.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Bone Erosion Progression, All Completers That Previously Only Failed 1 b/tsDMARD | 3 Participants |
| Control | Bone Erosion Progression, All Completers That Previously Only Failed 1 b/tsDMARD | 9 Participants |
p-value: 0.009995% CI: [-34.7, -2.6]Cochran-Mantel-Haenszel
Other Pre-specified
Bone Erosion Progression, All Completers With Erosive Phenotype
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand. A total score for each pathology is generated by the summation of individual joint/bone scores as follows: * Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24. * Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250. * Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75. * CARLOS (cartilage loss): 25 joints each scored on a scale from 0 (no damage) to 4 (complete ankylosis or fusion), resulting in a total score from 0 to 100. The proportion of bone erosion progressors is the % subjects with an increase of \> 0.5 on the bone erosion score, comparing baseline to Week 12. An increase of \> 0.5 represents disease progression.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Bone Erosion Progression, All Completers With Erosive Phenotype | 10 Participants |
| Control | Bone Erosion Progression, All Completers With Erosive Phenotype | 17 Participants |
p-value: 0.015695% CI: [-38.1, -2.2]Cochran-Mantel-Haenszel
Other Pre-specified
Change in Erosion Score, All Completers
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Erosion Score, All Completers | 0.2 score on a scale | Standard Deviation 0.85 |
| Control | Change in Erosion Score, All Completers | 0.5 score on a scale | Standard Deviation 1.74 |
p-value: 0.061895% CI: [-0.8, 0.1]Mixed Models Analysis
Other Pre-specified
Change in Erosion Score, All Completers That Previously Only Failed 1 b/tsDMARD
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Erosion Score, All Completers That Previously Only Failed 1 b/tsDMARD | 0.0 score on a scale | Standard Deviation 0.6 |
| Control | Change in Erosion Score, All Completers That Previously Only Failed 1 b/tsDMARD | 0.8 score on a scale | Standard Deviation 2.57 |
p-value: 0.044195% CI: [-1.7, 0.1]Mixed Models Analysis
Other Pre-specified
Change in Erosion Score, All Completers With Erosive Phenotype
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Bone erosion: 25 bones each scored on a scale from 0 (0-10% eroded volume) to 10 (91-100% eroded volume), resulting in a total score from 0 to 250.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Erosion Score, All Completers With Erosive Phenotype | 0.3 score on a scale | Standard Deviation 1.09 |
| Control | Change in Erosion Score, All Completers With Erosive Phenotype | 1.1 score on a scale | Standard Deviation 2.51 |
p-value: 0.030895% CI: [-1.8, 0]Mixed Models Analysis
Other Pre-specified
Change in Osteitis Score, All Completers
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Osteitis Score, All Completers | 0.1 score on a scale | Standard Deviation 2.61 |
| Control | Change in Osteitis Score, All Completers | 0.8 score on a scale | Standard Deviation 4.13 |
p-value: 0.066295% CI: [-1.7, 0.2]Mixed Models Analysis
Other Pre-specified
Change in Osteitis Score, All Completers That Previously Only Failed 1 b/tsDMARD
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Osteitis Score, All Completers That Previously Only Failed 1 b/tsDMARD | -0.3 score on a scale | Standard Deviation 2.22 |
| Control | Change in Osteitis Score, All Completers That Previously Only Failed 1 b/tsDMARD | 1.1 score on a scale | Standard Deviation 4.92 |
p-value: 0.03595% CI: [-3.2, 0.1]Mixed Models Analysis
Other Pre-specified
Change in Osteitis Score, All Completers With Erosive Phenotype
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Osteitis: 25 bones scored on a scale from 0 (no osteitis) to 3 (68-100% of bone volume involved), resulting in a total score from 0 to 75.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Osteitis Score, All Completers With Erosive Phenotype | 0.2 score on a scale | Standard Deviation 3.74 |
| Control | Change in Osteitis Score, All Completers With Erosive Phenotype | 1.8 score on a scale | Standard Deviation 6.18 |
p-value: 0.04595% CI: [-3.9, 0.3]Mixed Models Analysis
Other Pre-specified
Change in Synovitis Score, All Completers
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Synovitis Score, All Completers | 0.0 score on a scale | Standard Deviation 1.64 |
| Control | Change in Synovitis Score, All Completers | 0.1 score on a scale | Standard Deviation 1.51 |
p-value: 0.287195% CI: [-0.6, 0.3]Mixed Models Analysis
Other Pre-specified
Change in Synovitis Score, All Completers That Previously Only Failed 1 b/tsDMARD
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Synovitis Score, All Completers That Previously Only Failed 1 b/tsDMARD | 0.1 score on a scale | Standard Deviation 0.81 |
| Control | Change in Synovitis Score, All Completers That Previously Only Failed 1 b/tsDMARD | 0.6 score on a scale | Standard Deviation 1.78 |
p-value: 0.0995% CI: [-1.1, 0.2]Mixed Models Analysis
Other Pre-specified
Change in Synovitis Score, All Completers With Erosive Phenotype
RAMRIS is a standardized system for RA MRI scoring of 4 different types of joint pathologies in the wrist and the hand (synovitis, bone erosion, osteitis, and cartilage loss). A total score for each pathology is generated by the summation of individual joint/bone scores: • Synovitis: 8 joints each scored on a scale from 0 = normal to 3 = severe, resulting in a total score from 0 to 24.
Time frame: Week 12
Population: ITT with MRI images at both Baseline and Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Synovitis Score, All Completers With Erosive Phenotype | -0.1 score on a scale | Standard Deviation 2.27 |
| Control | Change in Synovitis Score, All Completers With Erosive Phenotype | 0.0 score on a scale | Standard Deviation 1.77 |
p-value: 0.434595% CI: [-0.9, 0.7]Mixed Models Analysis
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 12
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission | 28 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission | 19 Participants |
p-value: 0.064895% CI: [-2.1, 17.7]Cochran-Mantel-Haenszel
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 36
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 39 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 40 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 79 Participants |
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 48
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 47 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 41 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 88 Participants |
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 33 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 36 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, All Completers | 69 Participants |
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 36
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 34 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 35 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 69 Participants |
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 48
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 36 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 33 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 69 Participants |
Other Pre-specified
Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented
The CDAI score is based on 4 items: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * EGA, evaluator's global assessment (0=best to 10=worst) The CDAI score is calculated as follows and ranges from 0 to 76: • CDAI = TJC28 + SJC28 + SGA + EGA The CDAI score corresponds to the current RA activity: * 0 to ≤ 2.8 Remission * \>2.8 to ≤ 10 Low disease activity (LDA) * \>10 to ≤ 22 Moderate disease activity * \> 22 High disease activity
Time frame: Week 24
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 33 Participants |
| Control | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 31 Participants |
| All (TOL+COL) | Clinical Disease Activity Index (CDAI) Low Disease Activity (LDA) or Remission, Non-augmented | 64 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 12
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission | 31 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission | 18 Participants |
p-value: 0.015495% CI: [1.2, 21.6]Cochran-Mantel-Haenszel
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 36 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 37 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 73 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 48
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 50 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 42 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 92 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 36
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 38 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 40 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, All Completers | 78 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 36
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 31 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 35 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 66 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 24
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 35 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 32 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 67 Participants |
Other Pre-specified
DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented
The Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) score is a composite index providing a measure of disease activity, comprising: * TJC28, tender joint count of 28 joints (scale 0=best to 28=worst) * SJC28, swollen joint count of 28 joints (scale 0=best to 28=worst) * SGA, subject global assessment (0=best to 10=worst) * hsCRP (mg/L), high sensitivity C-reactive protein concentration (mg/L) A total score ranges from 0 to 10 and is computed as follows: DAS28-CRP = 0.56 \* sqrt(TJC28) + 0.28 \* sqrt(SJC28) + 0.36 \* ln(CRP+1) + 0.014 \* SGA + 0.96 The DAS28-CRP score corresponds to the current RA activity: * 0 to \< 2.6 Remission * 2.6 to \< 3.2 LDA * 3.2 to ≤ 5.1 Moderate activity * \> 5.1 High activity
Time frame: Week 48
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 37 Participants |
| Control | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 32 Participants |
| All (TOL+COL) | DAS28-CRP Low Disease Activity (LDA) or Remission, Non-augmented | 69 Participants |
Post Hoc
Discontinuation of SetPoint System Therapy
Discontinuation means active stimulation was suspended or the SetPoint System Implant was removed
Time frame: Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Discontinuation of SetPoint System Therapy | 2 Participants |
| Control | Discontinuation of SetPoint System Therapy | 2 Participants |
| All (TOL+COL) | Discontinuation of SetPoint System Therapy | 4 Participants |
Post Hoc
Discontinuation of SetPoint System Therapy
Discontinuation means active stimulation was suspended or the SetPoint System Implant was removed
Time frame: Week 48
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Discontinuation of SetPoint System Therapy | 2 Participants |
| Control | Discontinuation of SetPoint System Therapy | 4 Participants |
| All (TOL+COL) | Discontinuation of SetPoint System Therapy | 6 Participants |
Post Hoc
Discontinuation of SetPoint System Therapy
Discontinuation means active stimulation was suspended or the SetPoint System Implant was removed
Time frame: Week 36
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Discontinuation of SetPoint System Therapy | 2 Participants |
| Control | Discontinuation of SetPoint System Therapy | 4 Participants |
| All (TOL+COL) | Discontinuation of SetPoint System Therapy | 6 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 48
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 66 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 67 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 133 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 64 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 72 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 136 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 36
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 68 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 67 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) MCID Response, All Completers | 135 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 48
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 41 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 49 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 90 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 24
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 56 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 62 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 118 Participants |
Other Pre-specified
Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented
HAQ-DI response based on the MCID of -0.22 from baseline. The HAQ-DI is a questionnaire validated for RA self-assessment by subjects that contains 20 questions in the following 8 functional areas: * Dressing and grooming * Arising * Eating * Walking * Hygiene * Reach * Grip * Common daily activities Scoring within each functional area is from 0 (without any difficulty) to 3 (unable to do). The total score is obtained by summing 8 area scores and dividing by 8. The total HAQ-DI score ranges from 0 to 3 and corresponds to the current degree of disability: * 0 to \< 1 Mild difficulties to moderate disability * 1 to \< 2 Moderate disability * 2 to 3 Severe to very severe disability
Time frame: Week 36
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 53 Participants |
| Control | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 51 Participants |
| All (TOL+COL) | Health Assessment Questionnaire Disability Index (HAQ-DI) Response (MCID -0.22), Non-augmented | 104 Participants |
Post Hoc
Persistence With SetPoint System as a Stand-alone Therapy
Therapy persistence means continuation of therapy after it is initiated.
Time frame: Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System as a Stand-alone Therapy | 96 Participants |
| Control | Persistence With SetPoint System as a Stand-alone Therapy | 99 Participants |
| All (TOL+COL) | Persistence With SetPoint System as a Stand-alone Therapy | 195 Participants |
Post Hoc
Persistence With SetPoint System as a Stand-alone Therapy
Therapy persistence means continuation of therapy after it is initiated.
Time frame: Week 36
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System as a Stand-alone Therapy | 89 Participants |
| Control | Persistence With SetPoint System as a Stand-alone Therapy | 88 Participants |
| All (TOL+COL) | Persistence With SetPoint System as a Stand-alone Therapy | 177 Participants |
Post Hoc
Persistence With SetPoint System as a Stand-alone Therapy
Therapy persistence means continuation of therapy after it is initiated.
Time frame: Week 48
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System as a Stand-alone Therapy | 77 Participants |
| Control | Persistence With SetPoint System as a Stand-alone Therapy | 81 Participants |
| All (TOL+COL) | Persistence With SetPoint System as a Stand-alone Therapy | 158 Participants |
Post Hoc
Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy
Therapy persistence is defined as the continuation of therapy after it is initiated.
Time frame: Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 120 Participants |
| Control | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 118 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 238 Participants |
Post Hoc
Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy
Therapy persistence is defined as the continuation of therapy after it is initiated.
Time frame: Week 36
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 120 Participants |
| Control | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 116 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 236 Participants |
Post Hoc
Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy
Therapy persistence is defined as the continuation of therapy after it is initiated.
Time frame: Week 48
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 120 Participants |
| Control | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 116 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy as a Stand-alone or Augmented Thereapy | 236 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a b/tsDMARD
Therapy persistence means the continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corti
Time frame: Week 36
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 25 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 22 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 47 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a b/tsDMARD
Therapy persistence means the continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corti
Time frame: Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 17 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 12 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 29 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a b/tsDMARD
Therapy persistence means the continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corti
Time frame: Week 48
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 32 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 28 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a b/tsDMARD | 60 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid
Therapy persistence means continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corticosteroi
Time frame: Week 24
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 9 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 8 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 17 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid
Therapy persistence means continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corticosteroi
Time frame: Week 36
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 7 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 9 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 16 Participants |
Post Hoc
Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid
Therapy persistence means continuation of therapy after it is initiated. Augmentation of study therapy means the addition of treatment for RA therapy to active stimulation applied after completion of Week 12 assessments, during open-label, long-term follow-up. Augmented therapy may be applied at any time during long-term follow-up. The decision about the need, type and timing of treatment is left to the discretion of the Co-PI Rheumatologist and the subject. Subjects combining active stimulation with the following additions to RA therapy fall into the augmented therapy subgroup for analysis of response rates for key efficacy endpoints at specific timepoints: * Prednisone equivalent \>10 mg/day. If average daily corticosteroid use exceeds 10 mg/day prednisone after a period (time from previous visit up to the day before the current visit), the subject is assigned to the augmented therapy subgroup for that visit. * Corticosteroid injection. If subject received a corticosteroi
Time frame: Week 48
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 16 Participants |
| Control | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 12 Participants |
| All (TOL+COL) | Persistence With SetPoint System Therapy Augmented With a csDMARD and/or Steroid | 28 Participants |
Other Pre-specified
Study Participants That Are Neither Satisfied Nor Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis
Patient satisfaction was assessed at Week 24 using five-point Likert rating scale: * I am very dissatisfied * I am somewhat dissatisfied * I am neither satisfied nor dissatisfied * I am somewhat satisfied * I am very satisfied
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Study Participants That Are Neither Satisfied Nor Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 14 Participants |
| Control | Study Participants That Are Neither Satisfied Nor Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 12 Participants |
| All (TOL+COL) | Study Participants That Are Neither Satisfied Nor Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 26 Participants |
Other Pre-specified
Study Participants That Are Somewhat to Very Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis
Patient satisfaction was assessed at Week 24 using five-point Likert rating scale: * I am very dissatisfied * I am somewhat dissatisfied * I am neither satisfied nor dissatisfied * I am somewhat satisfied * I am very satisfied
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Study Participants That Are Somewhat to Very Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 15 Participants |
| Control | Study Participants That Are Somewhat to Very Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 10 Participants |
| All (TOL+COL) | Study Participants That Are Somewhat to Very Dissatisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 25 Participants |
Other Pre-specified
Study Participants That Are Somewhat to Very Satisfied With the SetPoint System for Treatment of Rheumatoid Arthritis
Patient satisfaction was assessed at Week 24 using five-point Likert rating scale: * I am very dissatisfied * I am somewhat dissatisfied * I am neither satisfied nor dissatisfied * I am somewhat satisfied * I am very satisfied
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Study Participants That Are Somewhat to Very Satisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 90 Participants |
| Control | Study Participants That Are Somewhat to Very Satisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 92 Participants |
| All (TOL+COL) | Study Participants That Are Somewhat to Very Satisfied With the SetPoint System for Treatment of Rheumatoid Arthritis | 182 Participants |
Other Pre-specified
Study Participants That Would Recommend the SetPoint System to a Family Member or Friend
Patients were asked a question about whether they would recommend the SetPoint System to family and friends
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Study Participants That Would Recommend the SetPoint System to a Family Member or Friend | 108 Participants |
| Control | Study Participants That Would Recommend the SetPoint System to a Family Member or Friend | 110 Participants |
| All (TOL+COL) | Study Participants That Would Recommend the SetPoint System to a Family Member or Friend | 218 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, All Completers
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 24
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, All Completers | 53 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, All Completers | 65 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, All Completers | 118 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, All Completers
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 48
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, All Completers | 61 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, All Completers | 62 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, All Completers | 123 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, All Completers
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 36
Population: ITT, all completers
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, All Completers | 57 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, All Completers | 64 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, All Completers | 121 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Non-augmented
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 36
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 46 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 54 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 100 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Non-augmented
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 24
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 50 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 52 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 102 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Non-augmented
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 48
Population: Subgroup of subjects receiving active stimulation for 1 min once per day, whose study therapy has not been augmented, who completed assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 43 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 48 Participants |
| All (TOL+COL) | the American College of Rheumatology (ACR) 20 Response, Non-augmented | 91 Participants |
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Subjects With 1 Prior b/tsDMARD
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 12
Population: ITT, subgroup of subjects that previously failed 1 b/tsDMARD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Subjects With 1 Prior b/tsDMARD | 23 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Subjects With 1 Prior b/tsDMARD | 8 Participants |
p-value: 0.005495% CI: [7.1, 43.3]Cochran-Mantel-Haenszel
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Subjects With 2 Prior b/tsDMARD
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 12
Population: ITT, subgroup of subjects that previously failed 2 b/tsDMARD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Subjects With 2 Prior b/tsDMARD | 8 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Subjects With 2 Prior b/tsDMARD | 3 Participants |
p-value: 0.043795% CI: [-2.2, 42.9]Cochran-Mantel-Haenszel
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Subjects With 3 Prior b/tsDMARD
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 12
Population: ITT, subgroup of subjects that previously failed 3 b/tsDMARD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Subjects With 3 Prior b/tsDMARD | 3 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Subjects With 3 Prior b/tsDMARD | 6 Participants |
p-value: 0.164395% CI: [-51.1, 16]Cochran-Mantel-Haenszel
Other Pre-specified
the American College of Rheumatology (ACR) 20 Response, Subjects With >=4 Prior b/tsDMARD
Response is defined as achieving at least 20% improvement from baseline to Week 12 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/L).
Time frame: Week 12
Population: ITT, subgroup of subjects that previously failed \>=4 b/tsDMARD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | the American College of Rheumatology (ACR) 20 Response, Subjects With >=4 Prior b/tsDMARD | 9 Participants |
| Control | the American College of Rheumatology (ACR) 20 Response, Subjects With >=4 Prior b/tsDMARD | 12 Participants |
p-value: 0.41595% CI: [-24.1, 19.2]Cochran-Mantel-Haenszel