Systemic Lupus Erythematosus ArthritisPhase 2MEASURENCT03355482
MRI Evaluation Assessing Synovitis to Address the Unmet Need for Reliable Endpoints in SLE
A Phase 2 study testing Methylprednisolone in people with Systemic Lupus Erythematosus Arthritis, run by Oklahoma Medical Research Foundation at 1 site in United States.
Trial summary
This is an exploratory evaluation of MRI as a reliable, sensitive, and accurate outcome measure for clinical trials in SLE arthritis. Forty patients with SLE and moderate to severe synovitis (minimum of 3 tender and 3 swollen joints in wrists and hands) will be randomized to new or increased methotrexate therapy plus… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus Arthritis
- What is being tested?
- Methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2017to 16 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meeting 4 1997 revised ACR classification criteria or SLICC criteria for SLE.
- Have active polyarticular arthritis with a minimum of 3 tender and 3 swollen joints or tendons in the hands and wrists observed at the screening visit and a history consistent with BILAG 2004 "B" arthritis.
- Willing and able to receive weekly subcutaneous methotrexate and intramuscular steroid injections (or placebo injection) as per the protocol.
- Willing and able to stop current immunosuppressants.
- Willing and able to undergo MRI and other study procedures (including no known allergy to contrast material).
- Women of childbearing potential must have a negative pregnancy test at screening and baseline and be willing to use effective contraception after the screening visit until three months after the end of the study.
- People of any sex or gender 18 to 70 years of age.
Who cannot join
- Target Disease Exceptions: Patients with acute nephritis requiring induction therapy, CNS lupus (except chorea, cranial neuropathy, and resolving optic neuritis) or any lupus condition requiring cyclophosphamide, biologics, or IV steroids >/= 500 mg.
- Medical History and Concurrent Diseases:
- Patients incapable of understanding or completing study-related assessments.
- Patients with any condition, whether or not related to SLE, which, in the opinion of the investigator, might place a patient at unacceptable risk for participation in the study.
- Patients with a history of cancer in the last 5 years, other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ.
- Patients who, in the opinion of the investigator, currently abuse drugs or alcohol.
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- Patients with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before the informed consent document was signed.
- Patients who have received any live vaccines within 2 months of the anticipated first dose of study medication.
- Patients with any serious bacterial infection within the last 2 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (eg, chronic pyelonephritis, osteomyelitis, or bronchiectasis).
- Patients at risk for tuberculosis (TB). Patients with active TB within 3 years, even if treated; history of active TB > 3 years ago, unless documented prior anti-TB treatment appropriate in duration and type; current known or suspected active TB; and latent TB not successfully treated (≥ 4 weeks at baseline).
- Physical and Laboratory Test Findings:
- Patients must not be known to be positive for hepatitis B surface antigen.
- Patients who are known to be positive for hepatitis C antibody may participate if the presence of hepatitis C virus can be excluded by polymerase chain reaction or recombinant immunoblot assay at screening.
- Acute hemolytic anemia with hemoglobin < 7.0 g/dL or known change in Hg by 2.0 g/dL within the last two months unless due to SLE and stable for the past month
- WBC < 1500/mm3 (< 1.5 x 109/L) unless due to chronic lupus activity and stable for at least one month
- Platelets < 40,000/mm3 (< 3 x 109/L) (If less than 100,000 must have been stable (within a range of 10,000/mm3) either by historical testing of known chronic thrombocytopenic patients within two months of screening or in two tests during the screening period at least one week apart.
- Serum creatinine > 2 times the ULN or estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2
- Serum ALT or AST > 2.5 times the ULN. If currently on methotrexate, patients may repeat this test during the screening period or later rescreen.
- Any other laboratory test results that, in the opinion of the investigator, might place a patient at unacceptable risk for participation in the study.
- Allergies and Adverse Drug Reactions: Known allergy or a history, in the opinion of the investigator or patient, of an unacceptable adverse sensitivity to gadolinium, methotrexate or unacceptable difficulties tolerating intramuscular or subcutaneous injections. Patients may elect lower doses of Depomedrol (1/2 or ¼ the dose) however if there is concern about tolerability of the large dose injection.
- Prohibited Treatments and/or Therapies:
- Patients who have received treatment with an investigational biologic within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.
- Patients who have received cyclophosphamide within 3 months of the Day 1 dose or bolus parenteral steroids >/= 500 mg within 1 month of screening.
- Use of rituximab within 6 months prior to Day 1; if > 6 months have elapsed since last rituximab dose, reconstitution of total peripheral B cell counts to predosing range should be documented. If there were no predose levels obtained then B cell counts must be minimally 200 x 106/l which characterizes most SLE patients (Odendahl et al. J Immunol 2000;165:5970-5979).
- Ongoing treatment (after the baseline visit) with immune suppressants (such as azathioprine, mycophenolate mofetil, leflunomide, calcineurin inhibitors or belimumab). These may be stopped or tapered as soon as informed consent procedures have been completed at the screening visit.
- Prednisone > 20 mg po qd (or equivalent) at the time of the screening visit or > 10 mg po qd (or equivalent) at or after randomization (steroids will additionally be tapered during the study if tolerated). Hydroxychloroquine is not exclusionary if the investigator or patient is unwilling to stop it, but taper will also be encouraged if the patient improves. NSAIDS are not exclusionary, but patients will be asked not to take them on the morning of each monthly visit, until the visit is concluded.
- Other Exclusion Criteria:
- Prisoners or patients who are involuntarily incarcerated.
- Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- Known contraindication or intolerance or risk of MRI procedures (e.g. permanent pacemakers, cardioverter-defibrillators, other implanted electronic devices, aneurysm clips and other metal implants, procedure-limiting claustrophobia (unless mitigated by the circumstances of the testing MRI for small joints) and severe renal impairment (estimated GFR < 40 mL/min/1.73 m2).
Trial locations and contacts
1 site in 1 country.
About this study
This is an exploratory evaluation of MRI as a reliable, sensitive, and accurate outcome measure for clinical trials in SLE arthritis. Forty patients with SLE and moderate to severe synovitis (minimum of 3 tender and 3 swollen joints in wrists and hands) will be randomized to new or increased methotrexate therapy plus a single injection of Depomedrol or a matched placebo at baseline. Methotrexate will be injected subcutaneously once per week at ascending doses. The study will evaluate a range of outcomes discernable by MRI at 3 months and 6 months after baseline. We will also compare MRI findings, clinical endpoints, and biomarker changes in patients that were treated with Depomedrol vs. matched placebo at baseline.
Read the detailed description
This will be a six month, double blind, randomized, placebo- controlled trial of subcutaneous methotrexate vs methotrexate plus baseline Depomedrol in patients with SLE and >/= 3 tender and 3 swollen joints in the hands and wrists. Patients who are already taking methotrexate </= 15 mg/week may qualify and will have a >/= 2.5 mg/week dose increase at baseline, receiving subcutaneous dosing whether on oral or sc dosing prior to entry. Those not taking methotrexate at baseline will initiate open label treatment in ascending doses beginning at 15 mg/week. All patients will increase methotrexate weekly up to 25 mg as tolerated or until resolution of arthritis. Decreases are allowed as needed.
After randomization, patients may choose to stop or continue any NSAIDs, hydroxychloroquine, or up to 10 mg prednisone if these were being used at screening. All other lupus-specific treatments or medications will be withdrawn. Optimization of methotrexate dose must be completed by Month 2. If additional immune- suppressive medications or steroids become necessary during the trial, patients remain evaluable for the primary endpoint, which is defined by clinical response regardless of treatment. In secondary analyses of Depomedrol vs. placebo, patients treated with rescue interventions will be censored when comparing changes in mean/median synovitis, osteitis RAMRIS or tendinitis scores in the two treatment groups, and they will be included as non- responders in dichotomous endpoints (SRI-4, BICLA). These analyses will also provide useful data for many of the other endpoints (comparisons of MRI vs joint counts and other measures which are valid regardless of treatment). Thus, although off protocol medications will not be encouraged, they will not require removal from the study.
- Conditions
- Systemic Lupus Erythematosus Arthritis
- Being tested
- Methylprednisolone, Placebos
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
160mg IM at baseline
PlacebosDrug
IM saline injection at baseline
| Study group | Role | What they receive |
|---|---|---|
| Depomedrol arm | Active comparator | Patients are treated with new or ascending doses of subcutaneous methotrexate, and receive a single intramuscular dose of Depomedrol (160mg) at baseline. Receives: Drug: Methylprednisolone |
| Placebo arm | Sham comparator | Patients are treated with new or ascending doses methotrexate, and receive a single intramuscular placebo injection at baseline. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
combined MRI synovitis, osteitis and tendinitis score at 3 months compared to baseline in clinical responders
the sum of the MRI synovitis, osteitis and tendinitis scores at 3 months will be compared to baseline by paired t test for those patients with a clinical response to the treatment regimen (defined as>/= 50% decrease in tender and swollen joints and disease severity scored as BILAG C or D at the 3 month visit). Each MRI parameter will be scored semi-quantitatively according to the OMERACT RA-MRI scoring system (RAMRIS) on a scale of 0-3, with 0=normal, 1=mild, 2=moderate, 3=severe involvement.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2017
- Study start10 Apr 2017
- Primary completion16 Feb 2022
- Study completion16 Dec 2022
Why it stopped: poor recruitment, funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus Erythematosus ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oklahoma Medical Research Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03355482
- Sponsor's protocol ID
- 17-09
- Other IDs
- BMS IM101-636
- Acronym
- MEASURE
- Status last verified
- Feb 2024
- First submitted
- 22 Nov 2017
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MRI Evaluation Assessing Synovitis to Address the Unmet Need for Reliable Endpoints in SLE
- ClinicalTrials.gov ID
- NCT03355482
- Acronym / sponsor ID
- MEASURE / 17-09
- Conditions
- Systemic Lupus Erythematosus Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor recruitment, funding
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Oklahoma Medical Research FoundationUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 10 Apr 2017 (actual)
- Primary completion
- 16 Feb 2022 (actual)
- Study completion
- 16 Dec 2022 (actual)
- First posted
- 28 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an exploratory evaluation of MRI as a reliable, sensitive, and accurate outcome measure for clinical trials in SLE arthritis. Forty patients with SLE and moderate to severe synovitis (minimum of 3 tender and 3 swollen joints in wrists and hands) will be randomized to new or increased methotrexate therapy plus a single injection of Depomedrol or a matched placebo at baseline. Methotrexate will be injected subcutaneously once per week at ascending doses. The study will evaluate a range of outcomes discernable by MRI at 3 months and 6 months after baseline. We will also compare MRI findings, clinical endpoints, and biomarker changes in patients that were treated with Depomedrol vs. matched placebo at baseline.
Detailed description
This will be a six month, double blind, randomized, placebo- controlled trial of subcutaneous methotrexate vs methotrexate plus baseline Depomedrol in patients with SLE and >/= 3 tender and 3 swollen joints in the hands and wrists. Patients who are already taking methotrexate </= 15 mg/week may qualify and will have a >/= 2.5 mg/week dose increase at baseline, receiving subcutaneous dosing whether on oral or sc dosing prior to entry. Those not taking methotrexate at baseline will initiate open label treatment in ascending doses beginning at 15 mg/week. All patients will increase methotrexate weekly up to 25 mg as tolerated or until resolution of arthritis. Decreases are allowed as needed.
After randomization, patients may choose to stop or continue any NSAIDs, hydroxychloroquine, or up to 10 mg prednisone if these were being used at screening. All other lupus-specific treatments or medications will be withdrawn. Optimization of methotrexate dose must be completed by Month 2. If additional immune- suppressive medications or steroids become necessary during the trial, patients remain evaluable for the primary endpoint, which is defined by clinical response regardless of treatment. In secondary analyses of Depomedrol vs. placebo, patients treated with rescue interventions will be censored when comparing changes in mean/median synovitis, osteitis RAMRIS or tendinitis scores in the two treatment groups, and they will be included as non- responders in dichotomous endpoints (SRI-4, BICLA). These analyses will also provide useful data for many of the other endpoints (comparisons of MRI vs joint counts and other measures which are valid regardless of treatment). Thus, although off protocol medications will not be encouraged, they will not require removal from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Depomedrol arm | Active comparator | Drug: MethylprednisolonePatients are treated with new or ascending doses of subcutaneous methotrexate, and receive a single intramuscular dose of Depomedrol (160mg) at baseline. |
| Placebo arm | Sham comparator | Drug: PlacebosPatients are treated with new or ascending doses methotrexate, and receive a single intramuscular placebo injection at baseline. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Meeting 4 1997 revised ACR classification criteria or SLICC criteria for SLE.
- Have active polyarticular arthritis with a minimum of 3 tender and 3 swollen joints or tendons in the hands and wrists observed at the screening visit and a history consistent with BILAG 2004 "B" arthritis.
- Willing and able to receive weekly subcutaneous methotrexate and intramuscular steroid injections (or placebo injection) as per the protocol.
- Willing and able to stop current immunosuppressants.
- Willing and able to undergo MRI and other study procedures (including no known allergy to contrast material).
Key exclusion criteria (30 listed)
- Target Disease Exceptions: Patients with acute nephritis requiring induction therapy, CNS lupus (except chorea, cranial neuropathy, and resolving optic neuritis) or any lupus condition requiring cyclophosphamide, biologics, or IV steroids >/= 500 mg.
- Medical History and Concurrent Diseases:
- Physical and Laboratory Test Findings:
- Allergies and Adverse Drug Reactions: Known allergy or a history, in the opinion of the investigator or patient, of an unacceptable adverse sensitivity to gadolinium, methotrexate or unacceptable difficulties tolerating intramuscular or subcutaneous injections. Patients may elect lower doses of Depomedrol (1/2 or ¼ the dose) however if there is concern about tolerability of the large dose injection.
- Prohibited Treatments and/or Therapies:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylprednisolone160mg IM at baseline | Drug | Depomedrol arm |
| PlacebosIM saline injection at baseline | Drug | Placebo arm |
Primary outcome
combined MRI synovitis, osteitis and tendinitis score at 3 months compared to baseline in clinical responders
Time frame: 3 months
the sum of the MRI synovitis, osteitis and tendinitis scores at 3 months will be compared to baseline by paired t test for those patients with a clinical response to the treatment regimen (defined as>/= 50% decrease in tender and swollen joints and disease severity scored as BILAG C or D at the 3 month visit). Each MRI parameter will be scored semi-quantitatively according to the OMERACT RA-MRI scoring system (RAMRIS) on a scale of 0-3, with 0=normal, 1=mild, 2=moderate, 3=severe involvement.
Results and safety
The study was stopped early (reason given: poor recruitment, funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylprednisolone in people with Systemic Lupus Erythematosus Arthritis, run by Oklahoma Medical Research Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor recruitment, funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
combined MRI synovitis, osteitis and tendinitis score at 3 months compared to baseline in clinical responders (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.