NCT01638715

Brief Summary

The purpose of this study is to find biological response patterns of patients with rheumatoid arthritis to drugs with different biologic modes of action. This study should help to predict therapeutic responses and to find the right therapy for the right patient.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
115

participants targeted

Target at P50-P75 for phase_4 rheumatoid-arthritis

Timeline
Completed

Started May 2012

Longer than P75 for phase_4 rheumatoid-arthritis

Geographic Reach
4 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2012

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

July 3, 2012

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 12, 2012

Completed
6.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2018

Completed
Last Updated

October 31, 2018

Status Verified

October 1, 2018

Enrollment Period

6.3 years

First QC Date

July 3, 2012

Last Update Submit

October 30, 2018

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid ArthritisBiologic therapiesBiomarkerMode of Action

Outcome Measures

Primary Outcomes (1)

  • Absolute Change in the Simplified Disease Activity Index (SDAI)

    24 Weeks

Secondary Outcomes (13)

  • Relative Change in the SDAI in percent

    24 Weeks

  • Absolute and relative change in the Clinical Disease Activity Index (CDAI) in percent

    24 Weeks

  • Absolute and relative change in the Disease Activity Score 28 (DAS28) in percent

    24 weeks

  • Achieving an SDAI or CDAI response (50%, 70%, 85%)

    24 Weeks

  • Achieving a EULAR response (European League Against Rheumatism)

    24 Weeks

  • +8 more secondary outcomes

Study Arms (4)

Infliximab

EXPERIMENTAL

Infliximab (Remicade®) will be administered i.v.at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46.

Drug: Remicade

Abatacept

EXPERIMENTAL

Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: \<60 kg Body weight (BW): 500 mg; \>60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c.application at a dose of 125mg weekly.

Drug: Orencia

Tocilizumab

EXPERIMENTAL

Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week.

Drug: Ro-Actemra

Rituximab

EXPERIMENTAL

Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©).

Drug: Mabthera

Interventions

RemicadeDRUG

\- Infliximab (Remicade®) will be administered i.v. at a dose of 3 mg/kg at 0 and 2 weeks, and 5 mg/kg at weeks 6, 14, and 22, 30, 38, and 46.

Infliximab
OrenciaDRUG

\- Abatacept (Orencia®) will be given i.v. at weeks 0, 2, 4, and then every 4 weeks until week 48 at a weight adjusted dose: \<60 kg Body weight (BW): 500 mg; \>60-100 kg BW: 750 mg; alternatively, based on preference and shared decision between patient and physician, patients randomized to the abatacept arm may receive s.c. application at a dose of 125mg weekly.

Abatacept
Ro-ActemraDRUG

\- Tocilizumab (Ro-Actemra®) will be administered every 4 weeks at a dose of 8 mg/kg BW (maximum dose of 800 mg); The employed dosage will be calculated using manufacturer guidelines; alternatively, based on preference and shared decision between patient and physician, patients randomized to the tocilizumab arm may receive s.c. application at a dose of 162mg every week.

Tocilizumab
MabtheraDRUG

\- Rituximab (Mabthera®) will be given as 1000mg at weeks 0 and 2, and then repeated at weeks 24 and 26. Patients will receive 100 mg methylprednisolon i.v. before each infusion, as well as 1000mg paracetamol, as well as 50mg diphenhydramine hydrochloride (Dibondrin©).

Rituximab

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women, ≥18 and ≤75 years of age, capable of understanding and signing an informed consent.
  • 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)
  • Duration of RA ≤3 years
  • 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.
  • Clinical Disease Activity Index (CDAI)≥15 corresponding to moderate to severe disease activity.

You may not qualify if:

  • Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
  • Weigh more than 100 kg
  • Use glucocorticoids \>10 mg/day prednisone or equivalent
  • Have previously received other treatments for their rheumatic disease:
  • intra-muscular or intra-articular injection of steroids in the previous month.
  • monoclonal antibodies or antibody fragments, licenced or investigational
  • any investigational drug within 3 months prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
  • Azathioprine or other cytostatic drugs.
  • Have a history of receiving human/murine recombinant products or a known allergy to murine products.
  • Have documentation of seropositivity for human immunodeficiency virus (HIV), or a positive test for hepatitis B surface antigen or hepatitis C ¬antibodies.
  • Have hypergammaglobulinemia
  • Have a history of alcohol or substance abuse within the preceding 6 months.
  • Have or have had a known history of
  • serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
  • opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Gesundheitszentrum Mariahilf

Vienna, 1060, Austria

Location

AKH Wien

Vienna, 1090, Austria

Location

Krankenhaus Hietzing

Vienna, 1130, Austria

Location

Hanusch Krankenhaus

Vienna, 1140, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

Ordination Wels (Private Medical Office)

Wels, 4600, Austria

Location

Institute of Rheumatology

Prague, 12850, Czechia

Location

V. A. Nasonova Research Institute of Rheumatology

Moscow, 115522, Russia

Location

Kantonsspital St.Gallen, Klinik für Rheumatologie

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

  • Studenic P, Bond G, Kerschbaumer A, Becede M, Pavelka K, Karateev D, Stieger J, Puchner R, Mueller RB, Puchhammer-Stockl E, Durechova M, Loiskandl M, Perkmann T, Olejarova M, Luchikhina E, Steiner CW, Bonelli M, Smolen JS, Aletaha D. Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2022 Jul 6;61(7):2815-2825. doi: 10.1093/rheumatology/keab839.

    PMID: 34792562DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

InfliximabAbataceptRituximab

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmunoconjugatesAntibodies, Monoclonal, Murine-Derived

Study Officials

  • Daniel Aletaha, MD

    Medical University of Vienna

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 3, 2012

First Posted

July 12, 2012

Study Start

May 1, 2012

Primary Completion

August 1, 2018

Study Completion

August 1, 2018

Last Updated

October 31, 2018

Record last verified: 2018-10

Locations

CH(1)RU(1)CZ(1)AU(6)