Rheumatoid Arthritis
Conditions
Keywords
Phase 2a multiple ascending dose, Anti-Very Late Antigen-1
Brief summary
A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Escalating Doses of SAN-300 in Patients with Active Rheumatoid Arthritis with Inadequate Response to Disease-Modifying Anti-rheumatic Drug(s).
Interventions
DRUGSAN-300 0.5 mg/kg QW
DRUGSAN-300 1.0 mg/kg QW
DRUGSAN-300 2.0 mg/kg QOW
DRUGSAN-300 4.0 mg/kg QOW
DRUGSAN-300 4.0 mg/kg QW
DRUGPlacebo
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with RA for ≥ 6 months according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria 2010 2. 18 to 75 years of age, inclusive, at the time of informed consent 3. Swollen joint count of ≥ 6 (66-joint count) and tender joint count of ≥ 6 (68-joint count) at Screening and randomization 4. Inadequate response to therapy or discontinuation of therapy because of unacceptable toxicity from at least one prior traditional or biologic disease-modifying anti-rheumatic drug (DMARD) 5. Stable dose of methotrexate (≥ 15 mg/week and ≤ 25 mg/week) for ≥ 6 weeks before randomization
Exclusion criteria
1. Functional Class IV as defined by ACR classification of functional status in RA 2. History of significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty's syndrome) 3. History of malignancy or carcinoma in situ within the 5 years before Screening or any history of melanoma. Patients with history of excised or adequately treated non-melanoma skin cancer are eligible 4. Evidence of clinically significant uncontrolled concurrent diseases such as cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major diseases 5. History of recurrent clinically significant infections 6. Current active infection or serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within 3 months before randomization 7. History of severe allergic or anaphylactic reactions to other biologic agents 8. History of allergies to murine protein 9. Surgery within 3 months before randomization (other than minor cosmetic surgery or minor dental procedures) or plans for a surgical procedure during the Treatment Period or Follow-up Period 10. History of tuberculosis or latent infection currently undergoing treatment 11. History of malaria 12. Treatment regimen with prednisone that is either over 10 mg/day (or equivalent dose of another corticosteroid) or is not taken at a stable dose of ≤ 10 mg/day for at least 4 weeks before randomization 13. Intra-articular corticosteroid injection(s) within 4 weeks before randomization 14. Any live immunization/vaccination, including against Herpes zoster, within 4 weeks before randomization. Live vaccinations must also be avoided throughout the study 15. Abnormal laboratory value at Screening or Day -1 considered clinically significant 16. Positive for hepatitis C virus (HCV) antibody or hepatitis B surface antigen (HBsAg) 17. Positive for human immunodeficiency virus (HIV) antibody 18. History of tuberculosis or positive QuantiFERON®-TB Gold test (QFT)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 10 weeks | Adverse events data are collected during a 10-week period, which includes 6 weeks of treatment and 4 weeks of follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | Baseline, End of Treatment Visit (Week 7) | DAS28-CRP= 0.56 x sqrt(TJC28) x sqrt(SJC28) + 0.36 x ln(CRP+1) +0.014 x VAS +0.96 Where TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). CRP: The C-Reactive Protein level (in mg/l). VAS General Health Assessment (from 0=best to 100=worst). ln=natural log. sqrt = square root. Higher scores indicate worse outcome. |
| Number of Participants With American College of Rheumatology 20 (ACR20) Response. | End of Treatment Visit (Week 7) | A participant is considered to have an ACR20 response if there is an improvement of 20% in all of the following: * Swollen joint count (66 joints) * Tender joint count (68 joints) and * At least three of the following five assessments: * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Patient's assessment of physical function, as measured by the HAQ-DI * CRP |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | Baseline, End of Treatment Visit (Week 7) | HAQ assesses the degree of difficulty a participant has had in accomplishing tasks in eight functional areas, over the previous week. 1. dressing and grooming, 2. rising, 3. eating, 4. walking, 5. hygiene, 6. reach, 7. grip, 8. common daily activities. For each of these categories, participants report amount of difficulty they have in performing two or three specific activities. There are four possible responses for the HAQ questions: without ANY difficulty (0), with SOME difficulty (1), with MUCH difficulty (2) and UNABLE to do (3). Scores for each of the eight categories are calculated. HAQ is calculated by adjusting the score for each of these categories, if necessary, based upon the patient's use of an aid, device, or assistance for that category, totaling the sum of the category scores and dividing by the number of categories answered. HAQ can range from 0 to 3. Higher scores (greater level of difficulty) indicate worse outcome. |
| Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | Baseline, End of Treatment Visit (Week 7) | Bone Erosion detected by MRI of hand/wrist was scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) system. Bone erosion was scored 0-10, according to the proportion (in increments of 10%) of erosion of articular bone: 0: 0%, 1: 1%-10%, 2: 11%-20%, ……..10: 91%-100%. Higher scores (more erosion) indicate worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW SAN-300 0.5 mg/kg subcutaneous once weekly for six weeks | 6 |
| Cohort B - SAN-300 1.0 mg/kg QW SAN-300 1.0 mg/kg subcutaneous once weekly for six weeks | 7 |
| Cohort C - SAN-300 2.0 mg/kg QOW SAN-300 2.0 mg/kg subcutaneous every other week for six weeks | 6 |
| Cohort D - SAN-300 4.0 mg/kg QOW SAN-300 4.0 mg/kg subcutaneous every other week for six weeks | 6 |
| Cohort E - SAN-300 4.0 mg/kg QW SAN-300 4.0 mg/kg subcutaneous once weekly for six weeks | 6 |
| Placebo Placebo dosing | 10 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort A - SAN-300 0.5 mg/kg QW | Cohort B - SAN-300 1.0 mg/kg QW | Cohort C - SAN-300 2.0 mg/kg QOW | Cohort D - SAN-300 4.0 mg/kg QOW | Cohort E - SAN-300 4.0 mg/kg QW | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 2.82 | 60.9 years STANDARD_DEVIATION 1.65 | 59.2 years STANDARD_DEVIATION 4.87 | 49.0 years STANDARD_DEVIATION 6.59 | 55.5 years STANDARD_DEVIATION 4.42 | 57.5 years STANDARD_DEVIATION 2.85 | 56.6 years STANDARD_DEVIATION 1.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 4 Participants | 9 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 4 Participants | 5 Participants | 4 Participants | 8 Participants | 32 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 5 Participants | 9 Participants | 33 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 1 / 6 | 1 / 7 | 1 / 6 | 6 / 6 | 2 / 6 | 3 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 6 | 2 / 6 | 0 / 6 | 0 / 10 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse events data are collected during a 10-week period, which includes 6 weeks of treatment and 4 weeks of follow-up.
Time frame: 10 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW | Number of Participants With Adverse Events | 5 Participants |
| Cohort B - SAN-300 1.0 mg/kg QW | Number of Participants With Adverse Events | 4 Participants |
| Cohort C - SAN-300 2.0 mg/kg QOW | Number of Participants With Adverse Events | 2 Participants |
| Cohort D - SAN-300 4.0 mg/kg QOW | Number of Participants With Adverse Events | 6 Participants |
| Cohort E - SAN-300 4.0 mg/kg QW | Number of Participants With Adverse Events | 4 Participants |
| Placebo | Number of Participants With Adverse Events | 7 Participants |
Secondary
Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP)
DAS28-CRP= 0.56 x sqrt(TJC28) x sqrt(SJC28) + 0.36 x ln(CRP+1) +0.014 x VAS +0.96 Where TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). CRP: The C-Reactive Protein level (in mg/l). VAS General Health Assessment (from 0=best to 100=worst). ln=natural log. sqrt = square root. Higher scores indicate worse outcome.
Time frame: Baseline, End of Treatment Visit (Week 7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -4.433 units on a scale | Standard Error 1.2736 |
| Cohort B - SAN-300 1.0 mg/kg QW | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -3.663 units on a scale | Standard Error 0.9716 |
| Cohort C - SAN-300 2.0 mg/kg QOW | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -2.002 units on a scale | Standard Error 0.8276 |
| Cohort D - SAN-300 4.0 mg/kg QOW | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -3.818 units on a scale | Standard Error 1.9164 |
| Cohort E - SAN-300 4.0 mg/kg QW | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -2.928 units on a scale | Standard Error 1.9874 |
| Placebo | Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP) | -3.028 units on a scale | Standard Error 1.2505 |
Secondary
Number of Participants With American College of Rheumatology 20 (ACR20) Response.
A participant is considered to have an ACR20 response if there is an improvement of 20% in all of the following: * Swollen joint count (66 joints) * Tender joint count (68 joints) and * At least three of the following five assessments: * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Patient's assessment of physical function, as measured by the HAQ-DI * CRP
Time frame: End of Treatment Visit (Week 7)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 3 Participants |
| Cohort B - SAN-300 1.0 mg/kg QW | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 3 Participants |
| Cohort C - SAN-300 2.0 mg/kg QOW | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 1 Participants |
| Cohort D - SAN-300 4.0 mg/kg QOW | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 2 Participants |
| Cohort E - SAN-300 4.0 mg/kg QW | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 1 Participants |
| Placebo | Number of Participants With American College of Rheumatology 20 (ACR20) Response. | 3 Participants |
Other Pre-specified
Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline
Bone Erosion detected by MRI of hand/wrist was scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) system. Bone erosion was scored 0-10, according to the proportion (in increments of 10%) of erosion of articular bone: 0: 0%, 1: 1%-10%, 2: 11%-20%, ……..10: 91%-100%. Higher scores (more erosion) indicate worse outcome.
Time frame: Baseline, End of Treatment Visit (Week 7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | -0.73 units on a scale | Standard Error 0.496 |
| Cohort B - SAN-300 1.0 mg/kg QW | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | 0.25 units on a scale | Standard Error 0.214 |
| Cohort C - SAN-300 2.0 mg/kg QOW | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | 0 units on a scale | Standard Error 0 |
| Cohort D - SAN-300 4.0 mg/kg QOW | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | 0.13 units on a scale | Standard Error 0.125 |
| Cohort E - SAN-300 4.0 mg/kg QW | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | 0.22 units on a scale | Standard Error 0.222 |
| Placebo | Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline | 0.13 units on a scale | Standard Error 0.125 |
Other Pre-specified
Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI)
HAQ assesses the degree of difficulty a participant has had in accomplishing tasks in eight functional areas, over the previous week. 1. dressing and grooming, 2. rising, 3. eating, 4. walking, 5. hygiene, 6. reach, 7. grip, 8. common daily activities. For each of these categories, participants report amount of difficulty they have in performing two or three specific activities. There are four possible responses for the HAQ questions: without ANY difficulty (0), with SOME difficulty (1), with MUCH difficulty (2) and UNABLE to do (3). Scores for each of the eight categories are calculated. HAQ is calculated by adjusting the score for each of these categories, if necessary, based upon the patient's use of an aid, device, or assistance for that category, totaling the sum of the category scores and dividing by the number of categories answered. HAQ can range from 0 to 3. Higher scores (greater level of difficulty) indicate worse outcome.
Time frame: Baseline, End of Treatment Visit (Week 7)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - SAN-300 0.5 mg/kg QW | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | -0.333 units on a scale | Standard Error 0.335 |
| Cohort B - SAN-300 1.0 mg/kg QW | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | -0.018 units on a scale | Standard Error 0.064 |
| Cohort C - SAN-300 2.0 mg/kg QOW | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | -0.146 units on a scale | Standard Error 0.06 |
| Cohort D - SAN-300 4.0 mg/kg QOW | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | -0.313 units on a scale | Standard Error 0.313 |
| Cohort E - SAN-300 4.0 mg/kg QW | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | 0.042 units on a scale | Standard Error 0.07 |
| Placebo | Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI) | -0.111 units on a scale | Standard Error 0.129 |