Xolair (Omalizumab) for Treatment of Drug-induced Acute Tubulointerstitial Nephritis (AIN)

The investigators goal is to evaluate the role of XOLAIR® in treatment of Acute Tubulointerstitial Nephritis (AIN) with the goal of shortening the duration and dose of prednisone for treatment of drug-induced AIN. Currently there is no good treatment for drug-induced AIN. Prednisone is the standard treatment but is associated with many side-effects when used long-term and at high doses.

Study Overview

• Status: Withdrawn
• Conditions: Acute Interstitial Nephritis
• Intervention / Treatment: Drug: Omalizumab; Drug: Prednisone

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult subjects > 18 years old of both genders
2. Biopsy proven acute interstitial nephritis in the native kidneys without evidence of ischemic or glomerular pathology in the biopsy
3. Normal baseline creatinine defined as estimated GFR ≥ 60 ml/min/SA based on MDRD calculation within 1 year prior to renal biopsy
4. Serum creatinine elevation of > 0.3 mg/dL and/or doubling of serum creatinine compared to most recent documented creatinine available (at least within the last year)
5. No immunosuppressants in the last three months including prednisone
6. Women of childbearing potential not using the contraception method can be included as this is a one time dosing and has no known long-term effects.

Exclusion Criteria:

1. Unwillingness to give consent
2. Patients who are Pregnant (positive serum pregnancy test for females) or breast feeding
3. Documented history of an autoimmune disease
4. Inability or unwillingness to take prednisone for the prescribed duration and/or dose
5. Subjects suspected to have non-drug-induced AIN
6. Subjects not meeting the inclusion criteria
7. Subjects with contraindication to administration of omalizumab
8. Prior use of omalizumab
9. Severe hypersensitivity to omalizumab or any component of the product
10. Known elevated IgE level from other disease processes
11. Subjects taking (nonsteroidal antiinflammatory drug) NSAIDs chronically
12. Use of any other investigational agents in the last 30 days
13. Patients with severe medical condition(s) including metastatic cancer, terminal congestive heart failure, severe ischemic heart disease or any other medical condition in which life expectancy is less than 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Omalizumab and Prednisone; Omalizumab in addition to prednisone. Omalizumab will be given once subcutaneously at a dose of 375 mg within 24 hours after receiving prednisone Standard clinical therapy with prednisone.; Day 1-14: 60 mg/day 14 days (2 weeks); Day 15-28: 40 mg/day (2 weeks); Day 29-35: 30 mg/day (1 week); Day 36-42: 20 mg/day (1 week); Day 43-49: 10 mg/day (1 week); Day 50-56: 5 mg/day (1 week); Subjects will stop taking prednisone on day 57 If patients weigh less than 60 Kg, the dose will be adjusted accordingly (to equal 1mg/kg/day of prednisone as the starting dose).	Drug: Omalizumab; administration of a single dose together with the standard treatment; Other Names: Xolair; Drug: Prednisone; standard treatment; Other Names: Prednisolone
ACTIVE_COMPARATOR: Prednisone; Standard clinical therapy with prednisone.; Day 1-14: 60 mg/day 14 days (2 weeks); Day 15-28: 40 mg/day (2 weeks); Day 29-35: 30 mg/day (1 week); Day 36-42: 20 mg/day (1 week); Day 43-49: 10 mg/day (1 week); Day 50-56: 5 mg/day (1 week); Subjects will stop taking prednisone on day 57 If patients weigh less than 60 Kg, the dose will be adjusted accordingly (to equal 1mg/kg/day of prednisone as the starting dose).	Drug: Prednisone; standard treatment; Other Names: Prednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in serum creatinine	Baseline to three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean individual percentage drop in serum creatinine relative to entry creatinine levels		baseline to 3 months
Percentage of subjects returning to their usual baseline creatinine (+25%) or below		baseline to 3 months
Reduction in Neutrophil gelatinase-associated lipocalcin.	24 hours, 4 hours, and in 3 months after Xolair treatment	baseline to 3 months
Percentage of subjects requiring renal replacement therapy		baseline to 3 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Vesna D. Garovic, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2018
• Primary Completion (ACTUAL): September 28, 2018
• Study Completion (ACTUAL): September 28, 2018

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: July 2, 2013
• First Posted (ESTIMATE): July 9, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 6, 2018
• Last Update Submitted That Met QC Criteria: December 4, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Nephritis; Kidney; Renal disease; Interstitial Nephritis; Tubulointerstitial
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephritis; Nephritis, Interstitial; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Prednisolone; Prednisone; Omalizumab
• Other Study ID Numbers: 12-006797

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No