A study to evaluate the safety and efficacy of Blisibimod in IgA Nephropathy

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-001365-26-ES
• Date of registration: 27/03/2015
• Prospective Registration: Yes
• Primary sponsor: Anthera pharmaceuticals, Inc
• Public title: A study to evaluate the safety and efficacy of Blisibimod in IgA Nephropathy
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Evaluate the Efficacy and Safety of Blisibimod Administration in Subjects with IgA Nephropathy - BRIGHT-SC: Blisibimod Response in IGA following at-Home Treatment by Subcutaneous Administration
• Date of first enrolment: 27/05/2015
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001365-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belarus, Belgium, Brazil, Bulgaria, Canada, Czech Republic, France, Georgia, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Netherlands, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom

Contacts

• Name: Colin Hislop, MD
• Affiliation: Anthera pharmaceuticals, Inc

• Name: Colin Hislop, MD
• Affiliation: Anthera pharmaceuticals, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects are eligible for enrollment if they meet the following inclusion criteria:
1.Male or female age 18 ? 65 years of age, inclusive.
2.Historical documentation of biopsy-proven IgA nephropathy according to definitions specified in the Oxford classification of IgA nephropathy (Appendix B). Histology should include evidence of staining of IgA in glomeruli by immunofluorescence of immunoperoxidase. Evidence of mesangial hypercellularity, segmental glomerulosclerosis, or endocapilllary hypercellularity must also be present.
3.Treatment with a stable clinically-optimized dose of ACEI and/or ARB for at least 90 days prior to screening.
4.Proteinuria > or = 1g/24hr but < or = 6g/24hr or equivalent as measured by random urine protein:creatinine ratio at 2 consecutive time points measured 2-6 weeks apart prior to randomization. At least one of these measures must be collected during screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Subjects must NOT meet any of the following exclusion criteria:
1.Clinical or histologic evidence of lupus nephritis or membranoproliferative glomerulonephritis, or non-IgA-related glomerulonephritis.
2.Greater than 50% glomerulosclerosis or cortical scarring on renal biopsy or an Oxford Classification Score that includes T2.
3.Crescentic IgA nephropathy (> or =30%) or clinical evidence of rapidly progressive glomerulonephritis.
4.Henoch-Schonlein purpura resulting in nephropathy.
5.eGFR < or = 30 mL/min per 1.73 m2 in subjects with a qualifying biopsy within 1 year of screening, or eGFR < or = 40 mL/min per 1.73 m2 in subjects with a qualifying biopsy conducted more than 1 year before screening.
6.Blood uric acid > 1.5 times the upper limit of normal upon repeat testing at screening.
7.History or clinical evidence of cirrhosis, or liver disease with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x upper limit of normal upon repeat testing.
8.Poorly controlled hypertension (> or = 150/90 mmHg).
9.History of diabetes mellitus.
10.Known to be positive for human immunodeficiency virus (HIV) and/or positive at the screening visit for hepatitis B surface antigen, or hepatitis C virus.
11.History of Crohn?s disease or celiac sprue.
12.Anemia (hemoglobin <8 g/dL), neutropenia (< or = 1500 cells/?L), or thrombocytopenia (<75,000 cells/?L).
13.Malignancy within the past 5 years (other than a squamous or basal cell carcinoma of the skin which has been excised and considered cured). Those with history of malignancy greater than 5 years ago should provide evidence of remission or cure. Subjects with a history of cervical cancer may be included in the study with documented evidence of conization or cure within the last 3 years.
14.Active infection requiring hospitalization or treatment with parenteral antibiotics within the past 60 days, or history of repeated herpetic viral infections (defined as more than 2 episodes in the year prior to screening). Other chronic infectious history should be discussed with the Medical Monitor.
15.History of active tuberculosis (TB). History of latent TB infection is also excluded unless there is documentation of appropriate anti TB therapy per Centers for Disease Control (CDC) guidelines or local regulations. In addition, the subject must not have any clinical signs/symptoms of active TB.
16.History of treatment with oral or parenteral corticosteroids for the treatment of IgA nephropathy within 3 months of screening or immunosuppressants within 6 months prior to screening. Treatment with oral or parenteral corticosteroids for non-IgAN related disease may be permitted at any time prior to or during the trial (please refer to protocol section 5.3 for specific requirements).
17.History of treatment with a molecule that targets the B-cell pathway within the last 12 months (e.g. rituximab, belimumab).
18.Received transfusion, plasmapheresis or plasma exchange, IV immunoglobulin (IVIg), or live vaccines according to listed wash-out periods:
?Transfusion, IVIg, plasmapheresis or plasma exchange ? 90 days prior to screening
?Live vaccines ? 30 days prior to randomization
19.Females who are nursing, pregnant, intending to become pregnant or intending to nurse during the time of the study, or who have a positive pregnancy test at baseline. All sexually-active subjects of reproductive potential are required to use a reliable method of birth control. Females and males are required to us

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

IgA Nephropathy
MedDRA version: 17.1 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: Blisibimod Injection
Product Code: A-623 or AMG 623
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: blisibimod
CAS Number: 1236126-45-6
Current Sponsor code: A-623 or AMG-623
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: This study is divided into 2 parts (A and B). All subjects will be on stable, optimized therapy with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), and the analyses will compare the effects of blisibimod plus ACEI/ARB therapy with placebo plus ACEI/ARB therapy.

The objective of Part A (from randomization through Week 24) is to assess the effect of blisibimod treatment on proteinuria.

The objective of Part B is to follow subjects for the occurrence of end-stage renal disease (ESRD) clinical events. The analysis for ESRD clinical events will include events accrued in this study (during Parts A and B) as well as in other concurrent placebo-controlled trials with blisibimod in patients with IgA nephropathy (e.g. Study AN-IGN3331).

Primary end point(s): All efficacy analyses in this study will compare the effects of blisibimod plus ACEI/ARB therapy with placebo plus ACEI/ARB therapy. All analyses will seek to evaluate superiority of blisibimod over placebo.

Primary Endpoint in Part A
In Part A, the Proteinuria Efficacy Endpoint will compare the proportion of subjects with baseline proteinuria > or = 1 g/24hr achieving proteinuria ? 0.5g/24hr at 24 weeks.
For this analysis, proteinuria will be inferred from urinary protein:creatinine ratio determined at 2 consecutive time points including Week 24.

Timepoint(s) of evaluation of this end point: Week 24

Secondary Objective: Secondary objectives are to evaluate changes in proteinuria, immunoglobulins IgA, IgG, IgM, plasma cells, renal function, safety profile, requirement for steroid therapy and biomarker changes in subjects treated with blisibimod compared to placebo.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints to be evaluated at the end of Part A

Secondary end point(s): Secondary endpoints to be evaluated at the end of Part A include:
.The proportion of subjects achieving proteinuria < or = 1g/24hr at Week 24.
.Percent change in proteinuria from baseline to Week 24.
.The proportion of subjects with baseline proteinuria > or = 1 g/24hr who
achieve proteinuria < or = 0.5g/24hr at Week 36 amongst subjects who
electively discontinue study drug therapy at Week 24.
.Percent change in proteinuria from baseline to Week 36 amongst
subjects who electively discontinue study drug therapy at Week 24.
.The proportion of subjects with baseline proteinuria > or = 2g/24hr
achieving proteinuria < or = 1g/24hr at Week 24.
.Change in serum IgG from baseline to Week 24.
.Change in serum IgA from baseline to Week 24.
. Change in plasma cell counts from baseline to Week 24.
. Change from baseline in serum immunoglobulin IgM.
. Percent reduction from baseline in plasma cells and B-cell subsets.
. Percent reduction from baseline in complement C3 and C4.
. Proportion of subjects achieving proteinuria < or = 1g/24hr or a reduction in proteinuria of ?50% from baseline.
. Proportion of subjects with baseline proteinuria > or = 3g/24hr achieving proteinuria < or = 1g/24hr.
. Change in hematuria from baseline to Week 24.
. Population PK evaluation of the effects of covariate factors, including demographic and health factors, on blisibimod PK parameters.

Secondary ID(s)

2014-001365-26-CZ

AN-IGN3321

NCT02062684

Source(s) of Monetary Support

Anthera Pharmaceuticals, Inc.