Back to results(C2013-0302) Safety and Efficacy of Escalating Doses of SAN-300 in Patients With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SAN-300 0.5 mg/kg QW
SAN-300 1.0 mg/kg QW
SAN-300 2.0 mg/kg QOW
SAN-300 4.0 mg/kg QOW
SAN-300 4.0 mg/kg QW
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Phase 2a multiple ascending dose, Anti-Very Late Antigen-1
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with RA for ≥ 6 months according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria 2010
- 18 to 75 years of age, inclusive, at the time of informed consent
- Swollen joint count of ≥ 6 (66-joint count) and tender joint count of ≥ 6 (68-joint count) at Screening and randomization
- 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)
- Stable dose of methotrexate (≥ 15 mg/week and ≤ 25 mg/week) for ≥ 6 weeks before randomization
Exclusion Criteria:
- Functional Class IV as defined by ACR classification of functional status in RA
- History of significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty's syndrome)
- 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
- 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
- History of recurrent clinically significant infections
- Current active infection or serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within 3 months before randomization
- History of severe allergic or anaphylactic reactions to other biologic agents
- History of allergies to murine protein
- 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
- History of tuberculosis or latent infection currently undergoing treatment
- History of malaria
- 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
- Intra-articular corticosteroid injection(s) within 4 weeks before randomization
- Any live immunization/vaccination, including against Herpes zoster, within 4 weeks before randomization. Live vaccinations must also be avoided throughout the study
- Abnormal laboratory value at Screening or Day -1 considered clinically significant
- Positive for hepatitis C virus (HCV) antibody or hepatitis B surface antigen (HBsAg)
- Positive for human immunodeficiency virus (HIV) antibody
- History of tuberculosis or positive QuantiFERON®-TB Gold test (QFT)
Sites / Locations
- Santarus Clinical Investigational Site 1012
- Santarus Clinical Investigational Site 1004
- Santarus Clinical Investigational Site 1008
- Santarus Clinical Investigational Site 1011
- Santarus Clinical Investigational Site 1013
- Santarus Clinical Investigational Site 1003
- Santarus Clinical Investigational Site 1017
- Santarus Clinical Investigational Site 1009
- Santarus Clinical Investigational Site 1019
- Santarus Clinical Investigational Site 1014
- Santarus Clinical Investigational Site 1006
- Santarus Clinical Investigational Site 1001
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
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
Arm Description
SAN-300 0.5 mg/kg subcutaneous once weekly for six weeks
SAN-300 1.0 mg/kg subcutaneous once weekly for six weeks
SAN-300 2.0 mg/kg subcutaneous every other week for six weeks
SAN-300 4.0 mg/kg subcutaneous every other week for six weeks
SAN-300 4.0 mg/kg subcutaneous every other week for six weeks
Placebo dosing
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
Full Information
NCT ID
NCT02047604
First Posted
January 22, 2014
Last Updated
June 18, 2021
Sponsor
Bausch Health Americas, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02047604
Brief Title
(C2013-0302) Safety and Efficacy of Escalating Doses of SAN-300 in Patients With Rheumatoid Arthritis
Official Title
A Randomized, Double-blind, Placebo-Controlled, Multiple Ascending Dose 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).
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
February 23, 2017 (Actual)
Study Completion Date
March 23, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bausch Health Americas, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Phase 2a multiple ascending dose, Anti-Very Late Antigen-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A - SAN-300 0.5 mg/kg QW
Arm Type
Experimental
Arm Description
SAN-300 0.5 mg/kg subcutaneous once weekly for six weeks
Arm Title
Cohort B - SAN-300 1.0 mg/kg QW
Arm Type
Experimental
Arm Description
SAN-300 1.0 mg/kg subcutaneous once weekly for six weeks
Arm Title
Cohort C - SAN-300 2.0 mg/kg QOW
Arm Type
Experimental
Arm Description
SAN-300 2.0 mg/kg subcutaneous every other week for six weeks
Arm Title
Cohort D - SAN-300 4.0 mg/kg QOW
Arm Type
Experimental
Arm Description
SAN-300 4.0 mg/kg subcutaneous every other week for six weeks
Arm Title
Cohort E - SAN-300 4.0 mg/kg QW
Arm Type
Experimental
Arm Description
SAN-300 4.0 mg/kg subcutaneous every other week for six weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo dosing
Intervention Type
Drug
Intervention Name(s)
SAN-300 0.5 mg/kg QW
Intervention Type
Drug
Intervention Name(s)
SAN-300 1.0 mg/kg QW
Intervention Type
Drug
Intervention Name(s)
SAN-300 2.0 mg/kg QOW
Intervention Type
Drug
Intervention Name(s)
SAN-300 4.0 mg/kg QOW
Intervention Type
Drug
Intervention Name(s)
SAN-300 4.0 mg/kg QW
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
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
Secondary Outcome Measure Information:
Title
Change From Baseline in Disease Activity Score With 28-joint Count Using C-reactive Protein (DAS28-CRP)
Description
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)
Title
Number of Participants With American College of Rheumatology 20 (ACR20) Response.
Description
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)
Other Pre-specified Outcome Measures:
Title
Change From Baseline in the Health Assessment Questionnaire-Disease Index (HAQ-DI)
Description
HAQ assesses the degree of difficulty a participant has had in accomplishing tasks in eight functional areas, over the previous week.
dressing and grooming,
rising,
eating,
walking,
hygiene,
reach,
grip,
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)
Title
Bone Erosion Detected Using Magnetic Resonance Imaging (MRI) Findings of the Hand and Wrist - Change From Baseline
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with RA for ≥ 6 months according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria 2010
18 to 75 years of age, inclusive, at the time of informed consent
Swollen joint count of ≥ 6 (66-joint count) and tender joint count of ≥ 6 (68-joint count) at Screening and randomization
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)
Stable dose of methotrexate (≥ 15 mg/week and ≤ 25 mg/week) for ≥ 6 weeks before randomization
Exclusion Criteria:
Functional Class IV as defined by ACR classification of functional status in RA
History of significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty's syndrome)
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
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
History of recurrent clinically significant infections
Current active infection or serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within 3 months before randomization
History of severe allergic or anaphylactic reactions to other biologic agents
History of allergies to murine protein
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
History of tuberculosis or latent infection currently undergoing treatment
History of malaria
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
Intra-articular corticosteroid injection(s) within 4 weeks before randomization
Any live immunization/vaccination, including against Herpes zoster, within 4 weeks before randomization. Live vaccinations must also be avoided throughout the study
Abnormal laboratory value at Screening or Day -1 considered clinically significant
Positive for hepatitis C virus (HCV) antibody or hepatitis B surface antigen (HBsAg)
Positive for human immunodeficiency virus (HIV) antibody
History of tuberculosis or positive QuantiFERON®-TB Gold test (QFT)
Facility Information:
Facility Name
Santarus Clinical Investigational Site 1012
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Santarus Clinical Investigational Site 1004
City
El Cajon
State/Province
California
ZIP/Postal Code
92020
Country
United States
Facility Name
Santarus Clinical Investigational Site 1008
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Santarus Clinical Investigational Site 1011
City
San Leandro
State/Province
California
ZIP/Postal Code
94578
Country
United States
Facility Name
Santarus Clinical Investigational Site 1013
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
Santarus Clinical Investigational Site 1003
City
Palm Harbor
State/Province
Florida
ZIP/Postal Code
34684
Country
United States
Facility Name
Santarus Clinical Investigational Site 1017
City
Florissant
State/Province
Missouri
ZIP/Postal Code
63031
Country
United States
Facility Name
Santarus Clinical Investigational Site 1009
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Santarus Clinical Investigational Site 1019
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Santarus Clinical Investigational Site 1014
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Santarus Clinical Investigational Site 1006
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Facility Name
Santarus Clinical Investigational Site 1001
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
12. IPD Sharing Statement
Learn more about this trial
(C2013-0302) Safety and Efficacy of Escalating Doses of SAN-300 in Patients With Rheumatoid Arthritis
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