Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil

Lupus Nephritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01369628
• Other study ID #: EMR 700461_014
• Status: Terminated
• Phase: Phase 1
• First received: June 7, 2011
• Last updated: October 21, 2013
• Start date: June 2011

Study information

• Verified date: October 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: AEMPS
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Atacicept
Regimen 1: Atacicept 25 mg weekly for 12 weeks Regimen 2: Atacicept 75 mg weekly for 12 weeks Regimen 3: Atacicept 150 mg weekly for 12 weeks

Locations

Country	Name	City	State
United States	EMD Serono Inc., One Technology Place	Rockland	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The nature (preferred terms) and incidence of AEs	Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.	12 weeks	Yes
Primary	Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease	Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.	12 weeks	Yes
Primary	The frequency and severity of laboratory abnormalities	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.	12 weeks	Yes
Secondary	The nature (preferred terms) and incidence of AEs	Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.	36 weeks	Yes
Secondary	Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease	Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.	36 weeks	Yes
Secondary	The frequency and severity of laboratory abnormalities	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.	36 weeks	Yes

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