Clinical trial NCT03157037: Open-Label Phase II Study to Evaluate the Efficacy and Safety of IdeS in Anti-GBM Disease
Official title: Open-Label Phase II Study in Anti-GBM Disease (Goodpasture's Disease) With Adverse Renal Prognosis to Evaluate the Efficacy and Safety of IdeS - GOOD-IDES
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anti-Glomerular Basement Membrane Antibody Disease
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Hansa Biopharma AB
First posted: 2017-05-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-Label, Single Arm study
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability of IdeS in patients with severe anti-glomerular basement membrane (anti-GBM) disease receiving standard of care consisting of pulse-methylprednisolone, oral prednisolone and intravenous cyclophosphamide combined with plasma exchange (PLEX).

Detailed description: This is an Open-Label Phase 2 Study to Evaluate the Efficacy and Safety of IdeS in anti-GBM disease (Goodpasture's disease, i.e. GP) with Adverse Renal Prognosis. The primary efficacy objective is to evaluate the efficacy of an IdeS based regimen to salvage independent renal function measured as no need for dialysis at 6 months after IdeS treatment. The primary safety objective of this study is to evaluate the safety and tolerability of IdeS in patients with severe anti-GBM disease on background of standard care consisting of pulse-methylprednisolone, oral prednisolone and intravenous cyclophosphamide (CYC) combined with plasma exchange (PLEX). The patients will be followed during 6 months according to the study visit plan.

Eligibility criteria: Inclusion Criteria:

1. Anti-GBM antibodies detected by ELISA above a level that is considered toxic by the investigator using local laboratory. Patients double-positive for anti-GBM and anti-neutrophil cytoplasmic antibodies (ANCAs) may be entered in the trial, but only if their level of anti-GBM antibodies fulfil the criteria listed above.
2. Estimated glomerular filtration rate (eGFR) \<15 ml/min/1.73 m\^2 (by modification of diet in renal disease (MDRD) equation) or if the patient is non-responsive to standard treatment, and has lost \>15 ml/min/1.73 m\^2 after start of treatment
3. Haematuria on dipstick and/or urinary sediment
4. Male or female patients aged at least 18 years; Female patients of childbearing potential may participate if highly effective contraception is used during the study, according to Clinical Trials Facilitation and Coordination Group (CTFG) guidance \[18\], see also section 4.9 (pregnancy test should be performed before inclusion).
5. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; and
6. Judged to be otherwise healthy by the Investigator, based on medical history, physical examination, and clinical laboratory assessments. Patients with clinical laboratory values that are outside of normal limits (other than those specified in the Exclusion Criteria) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study.

Exclusion Criteria:

1. Anuria for more than 2 days (less than 200 ml during last 48 hours);
2. Dialysis dependency for more than 5 days (maximum 3 sessions before signing informed consent);
3. Ongoing moderate to severe pulmonary haemorrhage (or having ceased within the last two weeks), defined as requiring assisted ventilation, oxygen or blood transfusions.
4. Pregnancy.
5. Symptomatic congestive heart failure (NYHA class 2-4) and requiring prescription medication or clinically evident peripheral edema of cardiac origin;
6. Myocardial infarction, unstable angina or stroke within 3 months prior to screening;
7. Ongoing bacterial infection requiring antibiotic therapy or viral infection with Hepatitis B, C or HIV (up to 3 months old negative test results are accepted); or active tuberculosis as indicated by chest x-ray.
8. Patients should not have received investigational drugs within 30 days prior to screening or within 4 half-lives (whichever is longer); and
9. History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.

Primary outcomes:
measure: Number of Patients With Independent Renal Function at 6 Months
timeFrame: 6 months after dosing
Secondary outcomes:
measure: Number of Patients With Independent Renal Function at 3 Months
timeFrame: 3 months after dosing
measure: Renal Function at 3 and 6 Months
timeFrame: 3 and 6 months after imlifidase dosing
measure: Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR
timeFrame: Pre-imlifidase, 1, 3 and 6 months after imlifidase dosing
measure: Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits
timeFrame: Predose up to 6 months after dosing
measure: Number of Patients With Haematuria (Blood in Urine)
timeFrame: At 6 months after dosing
measure: Change in Proteinuria During the Study
timeFrame: Pre-imlifidase, 3 and 6 months after imlifidase dosing
measure: Number of PLEXs Needed Over Time
timeFrame: Pre-screening and up to Day 93 after imlifidase dosing
measure: Pharmacokinetics of Imlifidase (Cmax)
timeFrame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15
measure: Pharmacokinetics of Imlifidase (AUC)
timeFrame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15
measure: Pharmacokinetics of Imlifidase (t1/2)
timeFrame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15
measure: Pharmacokinetics of Imlifidase (CL)
timeFrame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15
measure: Pharmacokinetics of Imlifidase (Vz)
timeFrame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15
measure: Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG)
timeFrame: Pre-dose up to 6 months after imlifidase administration
measure: Anti-imlifidase Antibodies (ADA)
timeFrame: Up to 6 months after dosing
measure: Renal Histology
timeFrame: Before administration of imlifidase (0-33 days) and after administration of imlifidase (3-6 days)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Department of Internal Medicine IV (Nephrology and Hypertension)
city: Prague
country: Czechia
facility: Department of Department of nephrology, First Faculty of Medicine and General Teaching Hospital and Charles University in Prague, Czech Republic,
city: Copenhagen
country: Denmark
facility: Department of Department of Nephrology, Rigshospitalet, Copenhagen
city: Paris
country: France
facility: PH USI UNTR, service du Pr Rondeau, Hôpital Tenon
state: Paris Cedex 20
city: Grenoble
country: France
facility: Department of Nephrology, Hemodialysis, Apheresis, and Transplantation, CHUGA (centre hospitalier universitaire Grenoble-Alpes)
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille, Nephrology Service
city: Paris
country: France
facility: Nephrology Service CHU Bichat
city: Toulouse
country: France
facility: Department of Nephrology and Organ Transplant, CHU Rangueil
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Uppsala
country: Sweden
facility: Department of Nephrology, Uppsala University Hospital
Study officials:
affiliation: Linkoeping University
name: Mårten Segelmark, MD PhD Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berden AE, Ferrario F, Hagen EC, Jayne DR, Jennette JC, Joh K, Neumann I, Noel LH, Pusey CD, Waldherr R, Bruijn JA, Bajema IM. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477. Epub 2010 Jul 8.
citation: van Daalen EE, Jennette JC, McAdoo SP, Pusey CD, Alba MA, Poulton CJ, Wolterbeek R, Nguyen TQ, Goldschmeding R, Alchi B, Griffiths M, de Zoysa JR, Vincent B, Bruijn JA, Bajema IM. Predicting Outcome in Patients with Anti-GBM Glomerulonephritis. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):63-72. doi: 10.2215/CJN.04290417. Epub 2017 Nov 21.