Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis - Eculizumab

NCT01275287 | Withdrawn Phase 2

• 2 other identifiers: 10-2218P01DK058335
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity. ANCA vasculitis is an inflammation of the small vessels whereby ANCA antibodies inappropriately activate one's own white blood cells (neutrophils) and cause damage to the small blood vessels.

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Keywords

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Complement Activation

Outcome Measures

Primary Outcomes (1)

• Birmingham Vasculitis Activity Score (BVAS)

  Change in disease activity as measured by BVAS at 12 weeks.

  12 weeks

Secondary Outcomes (6)

• Complement levels elevation

  up to 52 weeks

• Birmingham Vasculitis Activity Score(BVAS)

  up to 52 weeks

• Normalisation of complement activation

  up to 52 weeks

• Change in complement levels

  from baseline to week 12

• change in complement levels 2

  up to 52 weeks

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here.

Drug: Standard of care treatment

Eculizumab arm

EXPERIMENTAL

Standard of care for ANCA vasculitis + eculizumab treatment Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here.

Drug: eculizumab

Interventions

Standard of care treatment DRUG

induction : pulse methyl prednisolone (7 mg/kg/day x3) then prednisone 1 mg/kg/day (not to exceed 60 mg/day) for 4 weeks, then taper over the following 12 weeks. Cyclophosphamide starting at 0.75 gm/m2 IV (decreased to 0.5 gm/m\^2 for patients \> than 70 or with estimated Glomerular Filtration Rate (eGFR) \< 20 ml/min) to be titrated up to 1 gm/m\^2 depending on the 2 week white blood count (WBC) nadir \> 3000 cell/μL. Subsequent cyclophosphamide will be given every 4 weeks for at least 2 more doses. Once complete remission for 2 months, patient may be switched from cyclophosphamide to maintenance therapy with azathioprine 1.5-2 mg/kg/day for 6-9 months (to a total of 12 months of therapy) . For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, if rituximab is indicated for the patient, he cannot participate in the study.

Also known as: cytoxan

Standard of care

eculizumab DRUG

In addition to conventional therapy, patients randomized to eculizumab will receive 600 mg by IV infusion over 35 minutes every 7 days for the first 4 weeks, then 900 mg by IV infusion for the fifth dose 7 days later (week 5), then 900 mg every 14 days thereafter, for a total of 9 doses (about 3 months of treatment). This dosing scheme is based on that used for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). The length of treatment is shorter than for PNH, based on a desire to target the addition of eculizumab to the period of maximal disease activity, while limiting the risks of infectious complications in this first pilot study.

Also known as: Soliris

Eculizumab arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a current or a history of positive ANCA by the ELISA technique.
• De novo or relapsing disease requiring immunosuppression.
• Patients must have evidence of active glomerulonephritis as evidenced by the presence of glomerular hematuria (dysmorphic Red Blood Cells (RBCs) or RBC casts) with or without an increase in serum creatinine.
• Patients will be eligible within 10 days of commencing induction therapy (i.e., they may have already received pulse methylprednisolone and first dose of cyclophosphamide).

You may not qualify if:

• Patients with severe renal failure: creatinine \> 6 mg/dL or receiving hemodialysis and/or receiving plasmapheresis therapy.
• Patients with severe pulmonary hemorrhage requiring ventilation and/or plasmapheresis therapy.
• Patients with active bacterial or viral infection.
• Absolute neutrophils count \< 1000/mm\^3 to minimize the risk of infections
• Hemoglobin \< 8.5 g/dL
• Prior therapy with a monoclonal antibody (for example rituximab)within the previous 6 months. Peripheral CD-20 B-cells count \<= 1% due to rituximab even longer than 6 months.
• Severe coexisting conditions precluding immunosuppressive therapy or conditions requiring intravenous antibiotic therapy.
• History of infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV, tuberculosis or syphilis.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Alexion Pharmaceuticals, Inc.: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

UNC Kidney Center

Chapel Hill, North Carolina, 27510-7155, United States

Location

Related Publications (1)

• Bala MM, Malecka-Massalska TJ, Koperny M, Zajac JF, Jarczewski JD, Szczeklik W. Anti-cytokine targeted therapies for ANCA-associated vasculitis. Cochrane Database Syst Rev. 2020 Sep 29;9(9):CD008333. doi: 10.1002/14651858.CD008333.pub2.

  PMID: 32990324 DERIVED

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Cyclophosphamide; eculizumab

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Patrick H Nachman, MD

  UNC Kidney Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2010
• First Posted: January 12, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 23, 2017

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)