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

Rheumatoid Arthritis Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02047604
• Other study ID #: C2013-0302
• Secondary ID: 2013-003719-23
• Status: Completed
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: March 23, 2017

Study information

• Verified date: June 2021
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: March 23, 2017
• Est. primary completion date: February 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	Santarus Clinical Investigational Site 1013	Brandon	Florida
United States	Santarus Clinical Investigational Site 1009	Brooklyn	New York
United States	Santarus Clinical Investigational Site 1019	Chapel Hill	North Carolina
United States	Santarus Clinical Investigational Site 1014	Charlotte	North Carolina
United States	Santarus Clinical Investigational Site 1004	El Cajon	California
United States	Santarus Clinical Investigational Site 1017	Florissant	Missouri
United States	Santarus Clinical Investigational Site 1008	Los Angeles	California
United States	Santarus Clinical Investigational Site 1001	Middleburg Heights	Ohio
United States	Santarus Clinical Investigational Site 1003	Palm Harbor	Florida
United States	Santarus Clinical Investigational Site 1012	Phoenix	Arizona
United States	Santarus Clinical Investigational Site 1006	Salisbury	North Carolina
United States	Santarus Clinical Investigational Site 1011	San Leandro	California

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
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.	10 weeks
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.	Baseline, End of Treatment Visit (Week 7)
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	End of Treatment Visit (Week 7)