Clarification of Abatacept Effects in SLE With Integrated Biologic and Clinical Approaches

NCT02270957 | Completed Phase 2 Results DMC

• 1 other identifier: OMRF 13-38
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double blind, placebo controlled trial of abatacept for the treatment of lupus arthritis and other manifestations of lupus. Patients with lupus and at least 3 tender and 3 swollen joints and \</= 20 mg prednisone have other background immune suppressants withdrawn at entry. They can elect to receive up to a total of 320 mg depomedrol (in two or more injections) between the screening visit and the visit 2 months after dosing begins. Abatacept (125 mg) or placebo is administered in weekly subcutaneous doses. After 3 months of treatment patients who are not responding may elect to receive open label abatacept with or without additional standard of care therapies. Such patients are considered non responders. The primary endpoint is the British Isles Lupus Assessment Group Index (BILAG)-linked Combined Lupus Assessment (BICLA) which will require a clinically significant improvement in arthritis and other active features of lupus

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)

  The British Isles Lupus Assessment Group Index is a scoring system for progress of disease activity over the prior month with a scoring system that rates each organ system as "A" or severe, "B" or moderate, "C" or mild vs no activity in the past month. To meet the BICLA endpoint requires all baseline severe features (BILAG A) improving to moderate (BILAG B), mild or resolved, and all baseline BILAG B features improving to mild or resolved without increase in any other feature on either the BILAG or a different measure called the SLEDAI (SLE Disease Activity Index). Furthermore there must be no increase in Physician's Global Assessment or any rescue medications after the month 2 visit. Only those meeting all of these criteria meet the primary endpoint.

  6 months

Study Arms (2)

Abatacept

ACTIVE COMPARATOR

Patients receive Abatacept 125 mg subcutaneously weekly for six months. An optional continuation up until 12 months is allowed. Background immune suppressants are withdrawn at the beginning of the study and the option of depomedrol up to 320 mg total (in divided doses) is allowed at any time up through the visit 2 months after study medication is started. After this additional rescue is allowed with any standard of care treatment and/or open label abatacept (since patients are blinded) but this additional rescue will define non-response in the primary endpoint at six months.

Biological: Abatacept

Placebo

PLACEBO COMPARATOR

Patients receive placebo instead of Abatacept in a double blind fashion. Otherwise participation is the same, including that at the time of treatment failure they may elect any standard of care treatment and/or to begin taking open label abatacept but this rescue will define non-response in the primary endpoint at six months.

Other: Placebo

Interventions

Abatacept BIOLOGICAL

Also known as: Orencia

Abatacept

Placebo OTHER

Placebo

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• Four 1997 revised ACR Classification Criteria for SLE
• Active polyarticular arthritis meeting at minimum BILAG 2004 B definition with a minimum of 3 tender and 3 swollen joints observed at the screening visit
• Men and women 18 to 70 years of age.
• Women of childbearing potential and men with partners of childbearing potential must use an acceptable method of birth control throughout the study
• Women of childbearing potential must have a negative urine pregnancy test at screening and Study Day 1 (baseline visit) and may not be breast feeding

You may not qualify if:

• Current severe, organ-threatening disease (e.g. acute nephritis appropriate for induction therapy, CNS lupus (excepting chorea, cranial neuropathy, and resolving optic neuritis) or any lupus condition requiring cyclophosphamide, biologic therapy, or IV bolus steroids of \>/= 500 mg.
• Subjects who are incapable of understanding or completing study-related assessments.
• Subjects with any condition, whether or not related to SLE, which, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
• Subjects 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.
• Subjects who currently abuse drugs or alcohol.
• Subjects with acute herpes zoster or cytomegalovirus (CMV) within 2 months of screening.
• Subjects who have received any live vaccines within 3 months of first dose.
• Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection (eg, chronic pyelonephritis, osteomyelitis, or bronchiectasis).
• Subjects at risk for tuberculosis (TB).
• Subjects known to be positive for hepatitis B surface antigen or hepatitis C unless negative by PCR or RIBA
• Acute hemolytic anemia with hemoglobin \< 7.0 g/dL or known change in Hg by 2.0 g/dL within four months
• WBC \< 2500/mm3 (\< 3 x 109/L) unless due to chronic stable lupus activity
• Platelets \< 40,000/mm3 (\< 3 x 109/L) (If less than 100,000 must have been stable (within a range of 10,000/mm3 ) within two months of screening or in two tests during the screening period.
• Serum creatinine \> 2 times the ULN
• Serum ALT or AST \> 2.5 times the ULN

Sponsors & Collaborators

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

Study Sites (1)

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (2)

• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

  PMID: 33687069 DERIVED

• Thanou A, James JA, Arriens C, Aberle T, Chakravarty E, Rawdon J, Stavrakis S, Merrill JT, Askanase A. Scoring systemic lupus erythematosus (SLE) disease activity with simple, rapid outcome measures. Lupus Sci Med. 2019 Dec 30;6(1):e000365. doi: 10.1136/lupus-2019-000365. eCollection 2019.

  PMID: 31921432 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Joan T. Merrill, M.D.
• Organization: Oklahoma Medical Research Foundation

joan-merrill@omrf.org

405 822 2336

Study Officials

• Joan T Merrill, MD

  Oklahoma Medical Research Foundation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: October 13, 2014
• First Posted: October 22, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2021
• Last Updated: January 26, 2022
• Results First Posted: November 25, 2020

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: June 2021-May 2023
• Access Criteria: contact the PI at joan-merrill@omrf.org

Locations

US (1)