Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus Clinical Trial

— BOLD  

Official title:

Biomarkers of Lupus Disease: Study of Biomarker Changes Before and After Treatment With Depomedrol and Background Medication Withdrawal in Patients With Mild to Moderate SLE Disease Activity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987831
• Other study ID #: OMRF 09-02
• Secondary ID: Pfizer Inc
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 30, 2009
• Last updated: October 17, 2014
• Start date: May 2009
• Est. completion date: December 2012

Study information

• Verified date: October 2014
• Source: Oklahoma Medical Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Hypothesis: A reason for repeated disappointing outcomes of clinical trials testing targeted immune biologics for lupus may be the heterogeneity of the disease, exacerbated by the variable effects on immune homeostasis of the background medications that must be continued, in most study designs, in these flare-prone patients.

Purpose of Study: This study was designed to purposefully study a population equivalent to the placebo group of typical trials in SLE. In Group A patients entered the trial in mild-moderate flare, were treated with depomedrol, and any background immune suppressants withdrawn. Biomarkers at entry on various medications can be compared to biomarkers after steroid efficacy with background immune suppressants withdrawn. Depomedrol usually wears off over one to three months. Patients were closely observed, with serial biomarkers drawn at monthly intervals or immediately at the time of a new flare. Those patients developing new flares donated blood samples, were immediately treated as deemed appropriate, exiting the study. Group A was designed for up to 50 patients and recruited a total of 41. An additional group of 62 SLE patients donated blood once without additional interventions in order to increase the power of exploratory cross-sectional biomarker analysis on different immune suppressants (Group B). A control population of matched, healthy individuals donated blood twice for the same biomarker studies to validate these assays (Group C).

Description:

Original Protocol for Group A: Patients with at least a SLEDAI score of 6 or a BILAG score of B in at least two organ systems or A in at least one organ system were immediately entered into this study once informed consent was obtained. Background immune suppressants (if any) were stopped and in about half of the patients hydroxychloroquine was also stopped. All patients immediately received a shot of depomedrol 160 mg IM. Over the next two weeks they could elect up to three more shots of depomedrol for a total of four shots by the two week visit period. A complete battery of blood tests to assess lupus disease was drawn at the screening visit, and monthly thereafter. Exploratory biomarker studies were drawn as often as weekly for some markers and as often as three times in the study (landmark visits) for others. Protocol Changes during course of study: Biomarkers were drawn at Day zero, week 2 week 4 and monthly thereafter until flare. Patients who did not improve with protocol steroid treatments were withdrawn from Group A and immediately treated as warranted. Since there was no protocol-defined improving visit, they could not continue the protocol until flare. However their baseline samples were appropriate for study as part of Group B (see below).

Landmark visits for Group A are defined as: 1.) screening (pre-dose, on background meds with active disease) 2.) two weeks or four weeks after screening as optimal to assess a patient who has stopped background meds and is now maximally improved (but at least one grade drop in BILAG scores in all organs entered at A or B or a four point drop in SLEDAI, otherwise the participant is deemed a treatment failure and could not participate further in Group A. 3.) Flare visit on no background immune suppression defined as an increase in SLEDAI of 4 points from maximal improvement or one new BILAG moderate (B) score AND the investigator considers the condition to be a significant flare with intent to treat. Patients were (whenever possible) seen within 3 days for the flare visit if flare occured between monthly scheduled visits.

The primary purpose of this study was to evaluate the time to flare and safety of a treatment withdrawal protocol in patients with active, but non-organ threatening SLE. The following biomarkers were obtained for exploratory analysis: cytokine panel, B Cell studies, T Cell studies, autoantibody profiles, epigenetic and gene expression studies and flow cytometry studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 14 Years to 70 Years

Eligibility

Inclusion Criteria:

SLE Groups (Group A and B):

1. ACR criteria for SLE.

2. At least two organ systems moderately active to a minimum of BILAG B or SLEDAI score of 6.

Control group (Group C):

1. Age, ethnicity and gender matched (2:1) with an SLE study participant.

2. Free of active or major chronic disease as determined by brief history.

Exclusion Criteria:

1. Safety or circumstantial reasons why volunteer cannot comply with the protocol.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Other:
• Group B SLE one blood donation
Blood drawing, history, physical examination,medical record review, questionnaires, completion of disease activity measures including SLEDAI,BILAG, CLASI,PGA,PROs,LFA investigational systems, BICLA, SRI
• Blood drawing only Group C
Blood drawing and Brief medical history to ensure status of healthy control

Drug:
• Group A SLE prospective study
Patients have history and physical exmamination at each visit. Blood is drawn at each visit. At baseline, any background immune suppressant is stopped and patients given depomedrol up to 160 mg IM which can be repeated up to four times in the first two weeks. Patients are seen again at week 2, 4 and monthly until the final flare visit at which time they donate blood, receive appropriate treatments and exit study. Patients may elect to continue in study for up to one year. The following disease activity measures are included: SLEDAI, BILAG, CLASI, PGA, PROs (including lupus PRO and SF-36 ant ptGA), joint counts, exploratory outcome measures,BICLA,SRI

Locations

Country	Name	City	State
United States	Pfizer Inc	Collegeville	Pennsylvania
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Oklahoma Medical Research Foundation	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Flare Comparing Patients With Moderate vs Severe Disease Activity at Baseline	Group A only: patients on immunosuppressive treatments had them withdrawn at baseline. All patients were allowed up to 160 mg depomedrol at baseline which could be repeated within two weeks up to a total of 4 shots maximum or until satisfactory improvement. Time to flare was calculated from baseline. moderate disease at baseline was defined as up to 3 BILAG B (moderate disease) organ scores, no BILAG A (severe disease) score and a SLEDAI	12 months	No