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

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).

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; 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

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Santarus Clinical Investigational Site 1012
  • California
    • El Cajon, California, United States, 92020
      • Santarus Clinical Investigational Site 1004
    • Los Angeles, California, United States, 90048
      • Santarus Clinical Investigational Site 1008
    • San Leandro, California, United States, 94578
      • Santarus Clinical Investigational Site 1011
  • Florida
    • Brandon, Florida, United States, 33511
      • Santarus Clinical Investigational Site 1013
    • Palm Harbor, Florida, United States, 34684
      • Santarus Clinical Investigational Site 1003
  • Missouri
    • Florissant, Missouri, United States, 63031
      • Santarus Clinical Investigational Site 1017
  • New York
    • Brooklyn, New York, United States, 11201
      • Santarus Clinical Investigational Site 1009
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Santarus Clinical Investigational Site 1019
    • Charlotte, North Carolina, United States, 28210
      • Santarus Clinical Investigational Site 1014
    • Salisbury, North Carolina, United States, 28144
      • Santarus Clinical Investigational Site 1006
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Santarus Clinical Investigational Site 1001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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 painPatient's global assessment of disease activityPhysician's global assessment of disease activityPatient's assessment of physical function, as measured by the HAQ-DICRP	End of Treatment Visit (Week 7)

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): February 23, 2017
• Study Completion (Actual): March 23, 2017

Study Registration Dates

• First Submitted: January 22, 2014
• First Submitted That Met QC Criteria: January 24, 2014
• First Posted (Estimate): January 28, 2014

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Phase 2a multiple ascending dose, Anti-Very Late Antigen-1
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: C2013-0302; 2013-003719-23 (EudraCT Number)