MRI Evaluation Assessing Synovitis to Address the Unmet Need for Reliable Endpoints in SLE

NCT03355482 | Terminated Phase 2 FDA Drug

• 2 other identifiers: 17-09BMS IM101-636
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Systemic Lupus Erythematosus Arthritis

Outcome Measures

Primary Outcomes (1)

• 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.

  3 months

Study Arms (2)

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.

Drug: Methylprednisolone

Placebo arm

SHAM COMPARATOR

Patients are treated with new or ascending doses methotrexate, and receive a single intramuscular placebo injection at baseline.

Drug: Placebos

Interventions

Methylprednisolone DRUG

160mg IM at baseline

Depomedrol arm

Placebos DRUG

IM saline injection at baseline

Placebo arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Oklahoma Medical Research Foundation: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Access Health

Las Vegas, Nevada, 89128, United States

Location

MeSH Terms

Interventions

Methylprednisolone

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: November 28, 2017
• Study Start: April 10, 2017
• Primary Completion: February 16, 2022
• Study Completion: December 16, 2022
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

US (1)