Clinical trial NCT01369628: Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil
Official title: A Phase Ib, Multicenter, Open Label, Dose-Escalating, Repeat-Dose Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Atacicept When Administered to Subjects With Lupus Nephritis on a Stable Regimen of Mycophenolate Mofetil (MMF) With or Without Corticosteroids
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lupus Nephritis
Keywords: Open label
Dose Escalating
Phase Ib
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2011-06-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The sponsor electively terminated the study because the risk mitigation measures, deemed necessary after an unforeseen safety event, could not be effectively implemented within this protocol while maintaining study timelines within a reasonable time frame.

Detailed description: This study will evaluate atacicept's effects in subjects who have lupus nephritis, at least 2 g/day of protein in the urine, and are already taking mycophenolate mofetil. The evaluations will include the concentrations of atacicept in the blood, the effects of atacicept on immunoglobulins (antibodies), and any side effects. The first subjects will be given a low dose. Following periodic reviews of the trial data, subsequent subjects are planned to receive one of 2 progressively higher doses of atacicept.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects, ≥ 18 years of age, who provide written informed consent
* Subjects must have a diagnosis of SLE satisfying ≥ 4 of 11 ACR criteria, and must have had a renal biopsy during screening or within the previous 18 months demonstrating class III (A or A/C), IV (A or A/C), V, or concomitant III/V or IV/V LN as defined by the International Society of Nephrology/Renal Pathology Society (ISN/RPS).
* Subjects must have a urine protein: creatinine ratio ≥ 2 mg/mg (≥ 226.2 mg/mmol), and either a positive test for antinuclear antibody (ANA) (HEp-2 ANA ≥ 1:80) and/or anti-double stranded deoxyribonucleic acid (dsDNA) (≥ 30 IU/mL) at screening.
* Subjects must have started induction therapy for LN at least 5 months prior to Trial Day 1, be considered to have received continuous treatment for LN during the 5 months prior to Trial Day 1, and have received a stable dose of MMF ≥ 1 g/day, with or without corticosteroids, for at least 8 weeks prior to Trial Day 1.

Exclusion Criteria:

* Recent changes in immunosuppressant, ACD inhibitors for ARBs
* Use of azathioprine, cyclosporine, tacrolimus, or cyclophosphamide or other biologics within 8 weeks prior to Trial Day 1.
* Serum IgG \< 6 g/L
* Estimated Glomerular Filtration Rate (GFR) ≤ 30 mL/min per 1.73 m2
* History of Demyelinating Disease
* Significant Hematuria and/or Proteinuria due to a reason(s) other than LN. Evaluation should be done according to the local standard of care
* Breast feed or pregnancy
* Legal Incapacity or limited legal capacity

Primary outcomes:
measure: The nature (preferred terms) and incidence of AEs
timeFrame: 12 weeks
measure: Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
timeFrame: 12 weeks
measure: The frequency and severity of laboratory abnormalities
timeFrame: 12 weeks
Secondary outcomes:
measure: The nature (preferred terms) and incidence of AEs
timeFrame: 36 weeks
measure: Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
timeFrame: 36 weeks
measure: The frequency and severity of laboratory abnormalities
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Rockland
country: United States
facility: EMD Serono Inc., One Technology Place
state: Massachusetts
Study officials:
References: