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
Overview
- Phase
- Phase 1
- Intervention
- Atacicept
- Conditions
- Lupus Nephritis
- Sponsor
- EMD Serono
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- The nature (preferred terms) and incidence of AEs
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
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.
Investigators
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
- •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
Arms & Interventions
Arm 1
1 arm with the 3 following dose regimens: 1. Regimen 1: Atacicept 25 mg weekly for 12 weeks 2. Regimen 2: Atacicept 75 mg weekly for 12 weeks 3. Regimen 3: Atacicept 150 mg weekly for 12 weeks
Intervention: Atacicept
Outcomes
Primary Outcomes
The nature (preferred terms) and incidence of AEs
Time Frame: 12 weeks
Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.
The frequency and severity of laboratory abnormalities
Time Frame: 12 weeks
The incidence of subjects given each atacicept regimen who have shifts from Baseline in serum creatinine, serum albumin, urinary protein, or Hematology test (counts of white blood cells, neutrophils, lymphocytes, platelets) of at least 2 grades will be presented. Grading will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 toxicity grading, using the worst grade post-baseline during the 12-week treatment period.
Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
Time Frame: 12 weeks
Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.
Secondary Outcomes
- The nature (preferred terms) and incidence of AEs(36 weeks)
- The frequency and severity of laboratory abnormalities(36 weeks)
- Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease(36 weeks)