A Randomized, Multi-Center Biomarker Trial to Predict Therapeutic Responses of Patients With Rheumatoid Arthritis to a Specific Biologic Mode of Action

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01638715
• Date of registration: 03/07/2012
• Prospective Registration: No
• Primary sponsor: Medical University of Vienna
• Public title: A Randomized, Multi-Center Biomarker Trial to Predict Therapeutic Responses of Patients With Rheumatoid Arthritis to a Specific Biologic Mode of Action
• Scientific title: A Randomized, Multi-Center Biomarker Trial to Predict Therapeutic Responses of Patients With Rheumatoid Arthritis to a Specific Biologic Mode of Action
• Date of first enrolment: May 2012
• Target sample size: 115
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01638715
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Austria, Czech Republic, Czechia, Russian Federation, Saudi Arabia, Switzerland

Contacts

• Name: Daniel Aletaha, MD
• Affiliation: Medical University of Vienna

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Men and women, =18 and =75 years of age, capable of understanding and signing an
informed consent.

2. Classifiable RA according to the 2010 ACR/EULAR criteria (American College of
Rheumatology/European League Against Rheumatism classification criteria) or 1987 ARA
criteria (Criteria of American Rheumatology Association) (present or past) (2;3)

3. Duration of RA =3 years

4. Ongoing conventional DMARD therapy (Disease Modifying Antirheumatic Drugs) with
methotrexate (at least 20mg/week, or lower if not tolerated in higher doses) or
leflunomide (=100mg/week), for =6 months or =3 months with documented worsening of
disease activity.

5. Clinical Disease Activity Index (CDAI)=15 corresponding to moderate to severe disease
activity.

Exclusion Criteria:

1. Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have
little or no ability for self care.

2. Weigh more than 100 kg

3. Use glucocorticoids >10 mg/day prednisone or equivalent

4. Have previously received other treatments for their rheumatic disease:

1. intra-muscular or intra-articular injection of steroids in the previous month.

2. monoclonal antibodies or antibody fragments, licenced or investigational

3. any investigational drug within 3 months prior to screening or within 5
half-lives of the investigational agent, whichever is longer.

4. Azathioprine or other cytostatic drugs.

5. Have a history of receiving human/murine recombinant products or a known allergy to
murine products.

6. Have documentation of seropositivity for human immunodeficiency virus (HIV), or a
positive test for hepatitis B surface antigen or hepatitis C ¬antibodies.

7. Have hypergammaglobulinemia

8. Have a history of alcohol or substance abuse within the preceding 6 months.

9. Have or have had a known history of

1. serious infections (such as, but not limited to hepatitis, pneumonia, or
pyelonephritis) in the previous 3 months.

2. opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis
carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 12
months prior to screening.

3. a chronic or recurrent infectious disease (eg, chronic renal infection, chronic
chest infection, COPD, sinusitis, recurrent urinary tract infection, open,
draining or infected skin wound or ulcer etc.).

10. Have undergone any joint replacement surgery.

11. Be men and women of childbearing potential without use of adequate birth control
measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method
with spermicide, implantable or injectable contraceptives or surgical sterilization),
and willingness to continue this precaution for the duration of the study until 6
months after receiving the last medication.

12. Be considered ineligible according to the tuberculosis (TB) eligibility assessment and
screening, or show a positive test for latent Tbc using Quantiferon assay, unless
treatment with INH has been installed for at least 2 weeks prior to starting trial
drug.

13. Show evidence of malignancy, or lymphoproliferative disease, or any history of
malignancy within the previous 5 years, with the exception of basal cell or squamous
cell carcinoma of the skin that has been fully excised with no evidence of recurrence.

14. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic,
hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral
disease.

15. Be unable or unwilling to undergo multiple venipunctures because of poor tolerability
or lack of easy access.

16. Have presence of a transplanted solid organ (with the exception of a corneal
transplant > 3 months prior to screening).

17. Have a concomitant diagnosis or history of congestive heart failure (New York Heart
Association - NYHA - class III or IV) or diverticulitis.

18. Have a known history of a demyelinating disease, such as multiple sclerosis.

19. Be women who are pregnant, nursing, or planning pregnancy within 6 months after the
last infusion



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Mabthera

Drug: Remicade

Drug: Ro-Actemra

Drug: Orencia

Primary Outcome(s)

Absolute Change in the Simplified Disease Activity Index (SDAI) [Time Frame: 24 Weeks]

Secondary Outcome(s)

Change in sleep (Sleep Score on the Visual Analog Scale) [Time Frame: 24 Weeks]

Achieving an SDAI or CDAI response (50%, 70%, 85%) [Time Frame: 24 Weeks]

Change in quality of life (EuroQoL-5D, SF-36) [Time Frame: 24 weeks]

Absolute and relative change in the Disease Activity Score 28 (DAS28) in percent [Time Frame: 24 weeks]

Proportion achieving a low disease activity state (SDAI =11) [Time Frame: 24 Weeks]

Radiographic progression - (Van der Heijde/Sharp Score) [Time Frame: 6 months and 12 months]

Proportion achieving a remission state (SDAI =3.3) [Time Frame: 24 Weeks]

Relative Change in the SDAI in percent [Time Frame: 24 Weeks]

Absolute and relative change in the Clinical Disease Activity Index (CDAI) in percent [Time Frame: 24 Weeks]

Change in physical function (HAQ) [Time Frame: 24 Weeks]

Achieving a EULAR response (European League Against Rheumatism) [Time Frame: 24 Weeks]

Achieving an ACR response (20%, 50%, 70%) (American College of Rheumatology) [Time Frame: 24 Weeks]

Change in fatigue (Fatigue Score on the Visual Analog Scale) [Time Frame: 24 Weeks]

Secondary ID(s)

BIOBIO Study

2012-000139-21

Source(s) of Monetary Support

Please refer to primary and secondary sponsors