Working… Menu

Rituximab Objective Outcome Measures Trial in SLE (ROOTS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03054259
Recruitment Status : Recruiting
First Posted : February 15, 2017
Last Update Posted : May 1, 2019
Information provided by (Responsible Party):
University of Leeds

Tracking Information
First Submitted Date  ICMJE January 17, 2017
First Posted Date  ICMJE February 15, 2017
Last Update Posted Date May 1, 2019
Actual Study Start Date  ICMJE September 21, 2017
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
Feasibility of trial considering adherence to protocol, completion of all assessments and visits [ Time Frame: 26 weeks ]
Overall feasibility of the trial will be judged based on the feasibility variables. It is acknowledged that this trial incorporates multiple inter-related aspects of design, with many possible modifications in trials derived from it. Hence these numbers will be used as a guide only and specific target values have not been defined.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03054259 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • Proportion of patients achieving BILAG-based Composite Lupus Assessment (BICLA) [ Time Frame: 16 weeks ]
    An assesment of clinical efficacy of treatment
  • Proportion of patients achieving SLEDAI responder Index (SRI) [ Time Frame: 16 weeks ]
    An assesment of clinical efficacy of treatment
  • Number of serious adverse events [ Time Frame: 26 weeks ]
    Safety assessment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Rituximab Objective Outcome Measures Trial in SLE
Official Title  ICMJE A Feasibility Randomised Placebo-controlled Trial With Objective Outcome Measures to Evaluate the Efficacy of Biosimilar Rituximab in Musculoskeletal and Mucocutaneous Systemic Lupus Erythematosus
Brief Summary

This is a feasibility study to test a new trial design for an important drug in Systemic Lupus Erythematosus (SLE or "lupus").

SLE is an autoimmune disease. The immune system attacks the body's own tissues, any part of the body may be affected, but most commonly lupus causes a rash and arthritis, this affects patients' quality of life.

Lupus is usually treated with steroids or drugs that suppress the immune system. Although these help, many patients don't respond well enough and there is also concern for long term side effects. There is a new type of treatment called biologics. These target individual cells or molecules rather than the whole immune system and may be more effective with fewer side-effects. B cells are a part of the immune system that are known to play a role in lupus. There is already a biologic that removes these, called rituximab. In rheumatoid arthritis and vasculitis (similar to lupus), rituximab has been proven to be effective in clinical trials. However, in lupus clinical trials it did not seem to show any benefit. But many doctors and patients found that rituximab is effective, but the trials couldn't show this because of the way the drug's effects were measured. Therefore it is important that we test whether it truly is effective for lupus.

In this 6 month clinical study the investigators will look at lupus patients who have skin disease and arthritis as these are very common and randomise them to receive either rituximab or a placebo. Patients will have a careful clinical examination and undergo different methods to measure the effectiveness of the treatment. There are new versions to rituximab called "biosimilars". In this study biosimilar GP2013 will be used.

If this trial is successful a larger definitive study will be designed based on its results.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus Arthritis
Intervention  ICMJE
  • Drug: Rituximab
    1000mg rituximab infusions on days 1 and 15 (monoclonal antibody)
  • Drug: Methylprednisolone
    100mg infusion on days 1 and 15
  • Drug: Normal Saline
    250ml infusion on days 1 and 15
Study Arms  ICMJE
  • Experimental: Intervention
    2 x 1000mg Rituximab and 100mg methylprednisolone
    • Drug: Rituximab
    • Drug: Methylprednisolone
    • Drug: Normal Saline
  • Placebo Comparator: Control
    2 x 100mg methylprednisolone plus placebo
    • Drug: Methylprednisolone
    • Drug: Normal Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults aged at least 18 years old
  • Active musculoskeletal SLE defined by inflammatory musculoskeletal pain with either clinical synovitis, ultrasound tenosynovitis or positive power Doppler in at least 1 joint
  • No contraindication to the use of IV methylprednisolone, biosimilar rituximab, or any other required medications such as antipyretics and antihistamines
  • Willing to use appropriate contraception if at risk of pregnancy
  • Disease activity that is refractory to hydroxychoroquine, or patients unable to take hydroxychoroquine due to contra-indication or prior toxicity

Exclusion Criteria:

  • • Severe "critical" SLE flare defined as: (i) BILAG 2004 A flare in CNS system; (ii) BILAG 2004 A flare in the renal system; or (iii) any other SLE manifestation requiring more immunosuppression than allowed within the protocol in the physician's opinion

    • Pregnancy
    • Breast Feeding
    • Receipt of daily oral glucocorticoids greater than 10mg prednisolone or equivalent at screening or within the previous 5 days, or change in glucocorticoid dose in the previous 5 days.
    • Receipt of intramuscular or intravenous glucocorticoids within the past 4 weeks
    • Receipt of intravenous immunoglobulin, plasma exchange or cyclophosphamide within the last 3 months
    • Rituximab within the past 18 months or other biologic therapies within the past 6 months
    • Active infections, including but not limited to the human immunodeficiency virus, hepatitis B (including prior infection as judged by positive Hepatitis B core antibody) or hepatitis C
    • Serum IgG below the lower limit of the local laboratory range
    • Receipt of a live attenuated vaccine within 3 months prior to study enrolment
    • History of cancer in the past 5 years except for squamous or basal cell carcinoma that has been completely excised or treated cervical carcinoma in situ
    • In female participants, known history of cervical dysplasia CIN Grade III cervical high-risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) within the past 3 years. The patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality has been effectively treated >1 year ago)
    • Planned surgery within the study period that is expected to require overnight hospital admission
    • Any other concomitant medical condition that, in the investigator's opinion, or after discussion with the CI, places the participant at risk by participating in this study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Edward Vital, PhD 01133924396
Contact: James Goulding, MSc 01133924396
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03054259
Other Study ID Numbers  ICMJE RR15/197
2015-002688-40 ( EudraCT Number )
16/YH/0032 ( Other Identifier: Research Ethics Committee Reference Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Leeds
Study Sponsor  ICMJE University of Leeds
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Leeds
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP