A Randomized,Biomarker Trial to Predict Therapeutic Responses of Patients with Rheumatoid Arthritis to a Specific Biologic Mode of Action

• Register: EUCTR
• Last refreshed on: 15 October 2018
• Main ID: EUCTR2015-000581-58-CZ
• Date of registration: 16/06/2015
• Prospective Registration: Yes
• Primary sponsor: Revmatologicky ustav Praha
• Public title: A Randomized,Biomarker Trial to Predict Therapeutic Responses of Patients with Rheumatoid Arthritis to a Specific Biologic Mode of Action
• Scientific title: A Randomized, Biomarker Trial to Predict Therapeutic Responses of Patients with Rheumatoid Arthritis to a Specific Biologic Mode of Action - BioBio
• Date of first enrolment: 14/10/2015
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000581-58
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Czech Republic

Contacts

• Name: Coordinator
• Affiliation: Revmatologicky ustav Praha

• Name: Coordinator
• Affiliation: Revmatologicky ustav Praha

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 or 1987 ARA criteria (present or past)
3) Duration of RA =3 years
4) Ongoing conventional DMARD therapy with methotrexate (at least 20 mg/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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1) Be incapacitated, largely or wholly bedridden, or confined to a wheelchair, or have little or no ability for self care.
2) Telesná hmotnost nad 100 kg
3) Užívání glukokortikoidu >10 mg prednisonu denne nebo ekvivalentu
4) Predcházející lécba revmatického onemocnení:
a) intramusculární nebo intraartikulární injekce glukokortikoidu v posledním mesíci
b) monoklonální protilátky nebo jejich fragmenty, registrovanými nebo ve fázi klinického
zkoušení
c) jakékoliv léky ve fázi klinického zkoušení behem 5 mesícu nebo po dobu 5 polocasu zkoušeného
léku pred screeningem, podle toho, co je delší
d) Azathioprin nebo jiné cytotoxické látky
5) Podávání humánního/ myšího rekombinantního produktu nebo známá alergie na myší produkty v anamnéze.
6) Známá pozitivita viru lidské imunodeficience (HIV) nebo pozitivní antigen HBsAg nebo protilátky proti viru hepatitidy C.
7) Hypergamaglobulinémie pred screeningem
8) Anamnéza abúzu alkoholu nebo jiných látek v posledních 6 mesících.
9) Soucasné nebo minulé
a) serious infections (such as, but not limited to hepatitis, pneumonia, or pyelonephritis) in the
previous 3 months.
b) opportunistic infections (eg, herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis,
histoplasmosis, or mycobacteria other than TB) within 12 months prior to screening.
c) 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 (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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Remicade
Product Name: Remicade
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 100-

Trade Name: Orencia
Product Name: Orencia
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 250-

Trade Name: Ro-Actemra
Product Name: Ro Actemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumabum
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: up to
Concentration number: 20-

Trade Name: Mabthera
Product Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: up to
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Absolute change in the Simplified Disease Activity Index (SDAI) after 24 weeks.

Main Objective: To identify a set of clinical and/or biological markers that allows the identification of the optimal biological mode of action for a given patient with rheumatoid arthritis.
Primary endpoint: Absolute change in the Simplified Disease Activity Index (SDAI) after 24 weeks.

Timepoint(s) of evaluation of this end point: 24 weeks, 48 weeks

Secondary Objective: - Relative change in the SDAI after 24 weeks in percent.
- Absolute and relative change in the Clinical Disease Activity Index (CDAI) after 24 weeks in percent.
- Absolute and relative change in the Disease Activity Score 28 (DAS28) after 24 weeks in percent.
- Achieving an SDAI or CDAI response (50%, 70%, 85%)
- Achieving a EULAR response
- Achieving an ACR response (20%, 50%, 70%)
- Change in quality of life (EuroQoL-5D, SF-36) and physical function (HAQ)
- Change in fatigue and sleep
- Proportion achieving a low disease activity state (SDAI =11) after 24 weeks
- Proportion achieving a remission state (SDAI =3.3) after 24 weeks
- Radiographic progression over 6 months / 12 months

Secondary Outcome(s)

Secondary end point(s): - Relative change in the SDAI after 24 weeks in percent.
- Absolute and relative change in the Clinical Disease Activity Index (CDAI) after 24 weeks in percent.
- Absolute and relative change in the Disease Activity Score 28 (DAS28) after 24 weeks in percent.
- Achieving an SDAI or CDAI response (50%, 70%, 85%)
- Achieving a EULAR response
- Achieving an ACR response (20%, 50%, 70%)
- Change in quality of life (EuroQoL-5D, SF-36) and physical function (HAQ)
- Change in fatigue and sleep
- Proportion achieving a low disease activity state (SDAI =11) after 24 weeks
- Proportion achieving a remission state (SDAI =3.3) after 24 weeks
- Radiographic progression over 6 months / 12 months

Timepoint(s) of evaluation of this end point: 6 months, 12 Months

Secondary ID(s)

BioBioV4.0

Source(s) of Monetary Support

Medical University of Vienna