Open-Label Phase II Study to Evaluate the Efficacy and Safety of IdeS in Anti-GBM Disease

Mårten Segelmark15 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Anti-Glomerular Basement Membrane Antibody Disease

Interventions

ImlifidaseBIOLOGICAL

One dose of 0.25 mg/kg body weight imlifidase on study day 1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (10)

Department of Internal Medicine IV (Nephrology and Hypertension)

Innsbruck, Austria

Department of Department of nephrology, First Faculty of Medicine and General Teaching Hospital and Charles University in Prague, Czech Republic,

Prague, Czechia

Department of Department of Nephrology, Rigshospitalet, Copenhagen

Copenhagen, Denmark

Outcomes

Primary Outcomes

Number of Patients With Independent Renal Function at 6 Months

Number of patients without need for dialysis at 6 months. A patient with independent renal function is defined as a patient without need for dialysis.

Time frame: 6 months after dosing

Secondary Outcomes

Number of Patients With Independent Renal Function at 3 Months

Number of patients without need for dialysis at 3 months. A patient with independent renal function is defined as a patient without need for dialysis.

Time frame: 3 months after dosing

Renal Function at 3 and 6 Months

Estimated glomerular filtration rate (eGFR) is a measure of kidney function. eGFR was calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is above 90 mL/min/1.73m\^2. Reduced kidney function is characterised by a decreased eGFR value.

Time frame: 3 and 6 months after imlifidase dosing

Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR

eGFR is a measure of kidney function. eGFR has been calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is above 90 mL/min/1.73m\^2. Reduced kidney function is characterised by a decreased eGFR value. Number of patients per 4 different eGFR categories (0-15, 15-30, 30-60, ≥60 mL/min/1.73m\^2) are presented. A shift towards a higher category during the study indicates improved renal function over time.

Time frame: Pre-imlifidase, 1, 3 and 6 months after imlifidase dosing

Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits

Anti-GBM antibodies above a toxic level defined as \>20 U/mL. The level of anti-GBM antibodies was measured centrally using the Phadia ELiA(TM) anti-GBM kit. The enzyme-linked immunoassay (ELiA) is a fluorescence enzyme immunoassay.

Data from ClinicalTrials.gov

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