A Randomized, Double-Blind, Controlled, Phase II Multicenter Trial of CTLA41g (Abatacept) Plus Cyclophosphamide vs. Cyclophosphamide Alone in the Treatment of Lupus Nephritis.

Summary

Study Summary Text
This is a 1:1 randomized, double-blind, controlled phase II multicenter trial in individuals with lupus nephritis. Approximately 10 participants will be enrolled locally, and approximately 100 participants total will be enrolled among the 20 participating sites. The experimental group will receive abatacept 10 mg/kg IV at weeks 0, 2, and 4, then every 4 weeks until week 24; plus cyclophosphamide 500 mg IV q 2 weeks for 6 doses followed by azathioprine 2 mg/kg/day PO (rounded to nearest 25 mg and to a maximum dose of 200 mg) for 16 weeks. Participants randomized to the control group will receive abatacept placebo and cyclophosphamide followed by azathioprine as described for the experimental group. All participants will receive a prednisone regimen. The primary endpoint will be assessed at 24 weeks. Thereafter, subsequent therapy will depend on the study group and the nature of the response assessed at 24 weeks.

At week 28:
1.Experimental group participants:
a. Who achieve a complete response will discontinue abatacept and switch to overencapsulated azathioprine placebo up to week 52. This is intended to allow assessment of the durability of the response.

b. Who have no response will be terminated from the study and treated according to their physician’s best clinical judgment unless the site investigator judges the participant may benefit from continued participation. In this case, the participant may be proposed for continuation to the protocol chairs, medical monitor and clinical trial physician. If this group agrees, the participant will continue the treatment regimen as in (c) below. If this group disagrees, the participant will be terminated from the study and treated according to best clinical judgment.

c. Who achieve a partial response will continue abatacept up to week 48 and azathioprine up to week 52.

2.Control group participants:
a. Who achieve a complete response will discontinue abatacept placebo and switch to overencapsulated azathioprine up to week 52.
b. Who have no response will be terminated from the study and treated according to their physician’s best clinical judgment unless the site investigator judges the participant may benefit from continued participation. In this case, the participant may be proposed for continuation to the protocol chairs, medical monitor and clinical trial physician. If this group agrees, the participant will continue the treatment regimen as in (c) below. If this group disagrees, the participant will be terminated from the study and treated according to best clinical judgment.

c. Who achieve a partial response will continue abatacept placebo up to week 48 and azathioprine up to week 52.

Participant Eligibility

Patients must meet the following criteria to participate in the study:
1. Diagnosis of SLE by American College of Rheumatology (ACR) criteria
(http://www.rheumatology.org/practice/clinical/classification/SLE/1997_update_of_the_1982_acr_revised_criteria_for_classification_of_sle.pdf)
2. Positive antinuclear antibody (ANA) positive Anti-ds DNA test results at visit -1 or at any time within 14 days before visit -1.
3. Age 16 years or older.
4. Active lupus nephritis, as defined by
a. kidney biopsy documentation within the last 12 months of International Society of
Nephrology/Renal Pathology Society (ISN/RPS) proliferative nephritis
i. class III,
ii. class IV, or
iii. class V occurring in combination with classes III or IV; and
b. urine protein-to-creatinine ratio >1 at visit -1 or at any time within 14 days before visit
-1.
5. Ability to provide informed consent.