(C2013-0302) Safety and Efficacy of Escalating Doses of SAN-300 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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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).

Official Title
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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).

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: SAN-300 0.5 mg/kg QW
* Drug: SAN-300 1.0 mg/kg QW
* Drug: SAN-300 2.0 mg/kg QOW
* Drug: SAN-300 4.0 mg/kg QOW
* Drug: SAN-300 4.0 mg/kg QW
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A - SAN-300 0.5 mg/kg QW<br>SAN-300 0.5 mg/kg subcutaneous once weekly for six weeks | Drug: SAN-300 0.5 mg/kg QW<br> <br> |
| Experimental: Cohort B - SAN-300 1.0 mg/kg QW<br>SAN-300 1.0 mg/kg subcutaneous once weekly for six weeks | Drug: SAN-300 1.0 mg/kg QW<br> <br> |
| Experimental: Cohort C - SAN-300 2.0 mg/kg QOW<br>SAN-300 2.0 mg/kg subcutaneous every other week for six weeks | Drug: SAN-300 2.0 mg/kg QOW<br> <br> |
| Experimental: Cohort D - SAN-300 4.0 mg/kg QOW<br>SAN-300 4.0 mg/kg subcutaneous every other week for six weeks | Drug: SAN-300 4.0 mg/kg QOW<br> <br> |
| Experimental: Cohort E - SAN-300 4.0 mg/kg QW<br>SAN-300 4.0 mg/kg subcutaneous every other week for six weeks | Drug: SAN-300 4.0 mg/kg QW<br> <br> |
| Placebo Comparator: Placebo<br>Placebo dosing | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, End of Treatment Visit (Week 7) | 
| 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 | End of Treatment Visit (Week 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2a multiple ascending dose, Anti-Very Late Antigen-1