Therapeutic Drug Monitoring of Tocilizumab in Rheumatoid Arthritis

NCT03781310 | Unknown Phase 4 FDA Drug

• 1 other identifier: 0563-18-TLV
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: A wide range of serum trough concentrations is observed in tocilizumab-treated rheumatoid arthritis (RA) patients, while 1 mg/L tocilizumab is sufficient to block systemic interleukin-6 receptor. A substantial proportion of patients has higher serum tocilizumab concentrations and is likely to be overexposed. We expect that patients can at least reduce the dose aiming for a concentration of 5 mg/L without reducing efficacy. Objective: To evaluate the feasibility of the study after 20 weeks of follow-up, this includes the evaluation of the dose-reduction algorithm in tocilizumab-treated patients with RA. Study design: Double-blind randomized controlled pilot study with a follow up of 20 weeks. Study population: Consecutive RA patients that are treated with tocilizumab intravenously every four weeks for at least 24 weeks. Patients are screened for tocilizumab concentration after signing informed consent. Intervention: Patients with a concentration below 5 mg/L will continue the dose. Those patients with a tocilizumab concentration above 5 mg/L are randomly assigned (2:1) to dose reduction or to continuation of the standard care tocilizumab dose. In the intervention group, the precise dose-reduction is calculated per patient in order to achieve a tocilizumab concentration of 5 mg/L (range 4-6 mg/L). Main study parameters/endpoints: The feasibility of the study logistics is evaluated according to the dropout rate and patients opinion about the study. Second, the proportion of patients achieving the targeted tocilizumab concentration after dose reduction is evaluated. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Dose-reduction will lead to lower drug costs and possibly to reduce the risk of adverse events. Since we lower the tocilizumab concentration in a proportion of the patients, risk of a exacerbation of the disease exists. In this case, patients will receive their original dose. Previous studies showed that disease activity is controlled adequately after returning to the standard dose. However, our algorithm is designed to reach concentrations of 5 mg/L (range 4-6 mg/L) and studies showed that 1 mg/L of tocilizumab is sufficient to maintain clinical effect. The expected burden of this study is low, since study visits are planned at the time of infusion and therefore do not take extra time. The additional burden consists of an extra blood sample taken every visit and the fingerprick that is performed once.

Conditions

Rheumatoid Arthritis; Tocilizumab

Outcome Measures

Primary Outcomes (2)

• Disease flare rate

  Percent of patients experiencing a flare in RA disease activity according to DAS28-ESR score from week 0 until week 20.

  20 weeks

• Drop-out rate

  Percentage of patients completing 20-weeks on assigned treatment arm without withdrawing from the trial.

  20 weeks

Secondary Outcomes (10)

• DAS28 score

  20 weeks

• SDAI score

  20 weeks

• CDAI score

  20 weeks

• Swollen joint count

  20 weeks

• Tender joint count

  20 weeks

Study Arms (2)

Dose reduction

EXPERIMENTAL

Reduce the Tocilizumab dose at the baseline visit (week 0) and maintain that dose until 20 weeks of follow-up. The reduced dose is dependent of the tocilizumab serum concentration, measured at the screening visit, and is calculated according to the pre-defined dose-reduction algorithm.

Drug: Tocilizumab

Maintain dose

ACTIVE COMPARATOR

Maintain the original dose at baseline visit (week 0) until 20 weeks of follow-up.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

IV Tocilizumab once every 4 weeks at reduced dose according to algorithm.

Dose reduction; Maintain dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• RA according to the ACR 1987 or 2010 criteria;
• Current use of tocilizumab IV, with a consistent interval of 4 weeks for at least 24 weeks.
• years of age and older.

You may not qualify if:

• A potential subject will be excluded from participation in case of a scheduled surgery in the next 20 weeks or other preplanned reasons for treatment discontinuation.
• Children, pregnant women and individuals with a lack of judgement.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Amsterdam Rheumatology and Immunology Center: collaborator

Study Sites (1)

Department of Rheumatology, Tel Aviv Medical Center

Tel Aviv, 64239, Israel

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Uri Arad

  Tel-Aviv Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uri Arad

CONTACT

+972524262446; uria@tlvmc.gov.il

Sara Pel

CONTACT

+972524266605; sarap@tlvmc.gov.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research and Developemnt, Head

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 19, 2018
• Study Start: December 1, 2018
• Primary Completion: June 30, 2019
• Study Completion: December 1, 2019
• Last Updated: December 26, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)