Tocilizumab Dose Optimization in Rheumatoid Arthritis

2025-520513-30-00 Therapeutic use (Phase IV) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 6 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Authorised, recruitment pending
Participants planned 98
Countries 1
Sites 6

Rheumatoid arthritis

The main objective is to investigate the difference in mean time weighted Disease Activity Score in 28 joints, including erythrocyte sedimentation rate (DAS28-ESR) in patients with RA with serum trough concentrations higher than 15 mg/L who are randomly assigned to continuation of the standard dose or to increase dosin…

Key facts

Sponsor
Reade revalidatie & reumatologie centrum te Amsterdam
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Immune System Diseases [C20]
Decision date (initial)
2025-01-16
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2025-520513-30-00
EudraCT number
2018-004605-57

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic

The main objective is to investigate the difference in mean time weighted Disease Activity Score in 28 joints, including erythrocyte sedimentation rate (DAS28-ESR) in patients with RA with serum trough concentrations higher than 15 mg/L who are randomly assigned to continuation of the standard dose or to increase dosing interval to every two weeks.

Conditions and MedDRA coding

Rheumatoid arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Rheumatoid arthritis according to the ACR 1987 or 2010 criteria
  2. Current use of subcutaneous tocilizumab 162 mg weekly , for at least the last 6 months
  3. The treating rheumatologist is convinced of the benefit of tocilizumab continuation
  4. No changes in the treatment with glucocorticoids and DMARDs such as methotrexate in the past three months
  5. Written informed consent

Exclusion criteria 1

  1. A scheduled surgery in the next 52 weeks or other pre-planned reasons for treatment discontinuation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary objective of this study is to investigate the difference in mean time weighted DAS28 after 28 weeks between concentration-guided dose reduction and standard dosing. This analysis will be based on the non-inferiority principle, since we expect no worse outcome for patients in whom the dosing interval will be adjusted compared to patients who continue on the regular tocilizumab dose. As explained in the sample size calculation, the mean time weighted DAS28 is expected to be 2.8, with a

Secondary endpoints 11

  1. We will look at the difference in mean time weighted DAS28 after 52 weeks between the two treatment groups.
  2. The difference in CDAI, SDAI, and HAQ score after 28 weeks and 52 weeks between the two treatment groups
  3. The direct medical costs of TDM compared to the standard treatment regimen
  4. The difference in number of flares between the two treatment arms at 28 and 52 weeks
  5. The number and severity of adverse events in both treatment arms
  6. The difference in drug levels in the intervention group between week 0 and 52
  7. The change in drug levels from baseline after 52 weeks of intervention
  8. The relationship between dose, drug concentration, and clinical disease activity
  9. The therapeutic range of tocilizumab
  10. The development of a pharmacokinetic model resulting in a dashboard system
  11. The perspective of the patients about optimizing their dose with therapeutic drug monitoring

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Tocilizumab

SCP176238 · ATC

Active substance
Tocilizumab
Substance synonyms
RO4877533, BIIB800, ATLIZUMAB, TOCILIZUMABUM
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
162
Max total dose
162
Max treatment duration
1 Week(s)
Authorisation status
Authorised
ATC code
L04AC07 — TOCILIZUMAB
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Reade revalidatie & reumatologie centrum te Amsterdam

2 Total trials
Academic / Non-commercial
Sponsor organisation
Reade revalidatie & reumatologie centrum te Amsterdam
Address
Admiraal Helfrichstraat 1
City
Amsterdam
Postcode
1056 AA
Country
Netherlands

Scientific contact point

Organisation
Reade revalidatie & reumatologie centrum te Amsterdam
Contact name
Maureen Leeuw

Public contact point

Organisation
Reade revalidatie & reumatologie centrum te Amsterdam
Contact name
Maureen Leeuw

Locations

1 EU/EEA country · 6 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Authorised, recruitment pending 98 6
Rest of world 0

Investigational sites

Netherlands

6 sites · Authorised, recruitment pending
Noordwest Ziekenhuisgroep Stichting
Reumatologie, Wilhelminalaan 12, 1815 JD, Alkmaar
Reade revalidatie & reumatologie centrum te Amsterdam
Reumatologie, Admiraal Helfrichstraat 1, 1056 AA, Amsterdam
Maasstad Ziekenhuis Stichting
Reumatologie, Maasstadweg 21, 3079 DZ, Rotterdam
Amsterdam UMC Stichting
Reumatologie, De Boelelaan 1117, 1081 HV, Amsterdam
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Reumatologie, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Sint Maartenskliniek Stichting
Reumatologie, Hengstdal 3, 6574 NA, Ubbergen

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Onderzoeksprotocol 2025-520513-30-00 6
Recruitment arrangements (for publication) K1_Recruitement arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF TODORA adult 5
Summary of Product Characteristics (SmPC) (for publication) E2_SPC Tocilizumab 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-01-07 Netherlands Acceptable
2025-01-16
2025-01-16