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Rituximab Objective Outcome Measures Trial in SLE (ROOTS)

Primary Purpose

Systemic Lupus Erythematosus Arthritis

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Rituximab
Methylprednisolone
Normal Saline
Sponsored by
University of Leeds
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Lupus Erythematosus Arthritis

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Chapel Allerton Hospital- Leeds Institute for Rheumatic and Musculoskeletal MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Control

Arm Description

2 x 1000mg Rituximab and 100mg methylprednisolone

2 x 100mg methylprednisolone plus placebo

Outcomes

Primary Outcome Measures

Feasibility of trial considering adherence to protocol, completion of all assessments and visits
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.

Secondary Outcome Measures

Proportion of patients achieving BILAG-based Composite Lupus Assessment (BICLA)
An assesment of clinical efficacy of treatment
Proportion of patients achieving SLEDAI responder Index (SRI)
An assesment of clinical efficacy of treatment
Number of serious adverse events
Safety assessment

Full Information

First Posted
January 17, 2017
Last Updated
April 30, 2019
Sponsor
University of Leeds
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1. Study Identification

Unique Protocol Identification Number
NCT03054259
Brief Title
Rituximab Objective Outcome Measures Trial in SLE
Acronym
ROOTS
Official Title
A Feasibility Randomised Placebo-controlled Trial With Objective Outcome Measures to Evaluate the Efficacy of Biosimilar Rituximab in Musculoskeletal and Mucocutaneous Systemic Lupus Erythematosus
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 21, 2017 (Actual)
Primary Completion Date
February 2020 (Anticipated)
Study Completion Date
February 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leeds

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
2 x 1000mg Rituximab and 100mg methylprednisolone
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
2 x 100mg methylprednisolone plus placebo
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
1000mg rituximab infusions on days 1 and 15 (monoclonal antibody)
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
100mg infusion on days 1 and 15
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
250ml infusion on days 1 and 15
Primary Outcome Measure Information:
Title
Feasibility of trial considering adherence to protocol, completion of all assessments and visits
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients achieving BILAG-based Composite Lupus Assessment (BICLA)
Description
An assesment of clinical efficacy of treatment
Time Frame
16 weeks
Title
Proportion of patients achieving SLEDAI responder Index (SRI)
Description
An assesment of clinical efficacy of treatment
Time Frame
16 weeks
Title
Number of serious adverse events
Description
Safety assessment
Time Frame
26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Edward Vital, PhD
Phone
01133924396
Email
e.m.j.vital@leeds.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
James Goulding, MSc
Phone
01133924396
Facility Information:
Facility Name
Chapel Allerton Hospital- Leeds Institute for Rheumatic and Musculoskeletal Medicine
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edward Vital

12. IPD Sharing Statement

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Rituximab Objective Outcome Measures Trial in SLE

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