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

NCT03157037 | Completed Phase 2 Results DMC

• 1 other identifier: GOOD-IDES-01
• Study Type: interventional
• Target: 15
• Locations: 5 countries
• Sites: 10

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).

Conditions

Anti-Glomerular Basement Membrane Antibody Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months after dosing

Secondary Outcomes (15)

• Number of Patients With Independent Renal Function at 3 Months

  3 months after dosing

• Renal Function at 3 and 6 Months

  3 and 6 months after imlifidase dosing

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

  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

  Predose up to 6 months after dosing

• Number of Patients With Haematuria (Blood in Urine)

  At 6 months after dosing

Study Arms (1)

Imlifidase

EXPERIMENTAL

Imlifidase 0.25 mg/kg body weight intravenous infusion

Biological: Imlifidase

Interventions

Imlifidase BIOLOGICAL

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

Also known as: Immunoglobulin G-degrading enzyme of Streptococcus pyogenes, HMed-IdeS, IdeS

Imlifidase

Eligibility Criteria

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

You may qualify if:

• 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.
• 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
• Haematuria on dipstick and/or urinary sediment
• Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; and

You may not qualify if:

• Anuria for more than 2 days (less than 200 ml during last 48 hours);
• Dialysis dependency for more than 5 days (maximum 3 sessions before signing informed consent);
• Ongoing moderate to severe pulmonary haemorrhage (or having ceased within the last two weeks), defined as requiring assisted ventilation, oxygen or blood transfusions.
• Pregnancy.
• Symptomatic congestive heart failure (NYHA class 2-4) and requiring prescription medication or clinically evident peripheral edema of cardiac origin;
• Myocardial infarction, unstable angina or stroke within 3 months prior to screening;
• 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.
• Patients should not have received investigational drugs within 30 days prior to screening or within 4 half-lives (whichever is longer); and
• 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.

Sponsors & Collaborators

• Mårten Segelmark: lead
• Hansa Biopharma AB: collaborator

Study Sites (10)

Department of Internal Medicine IV (Nephrology and Hypertension)

Innsbruck, 6020, Austria

Location

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

Prague, 121 08, Czechia

Location

Department of Department of Nephrology, Rigshospitalet, Copenhagen

Copenhagen, 2100, Denmark

Location

PH USI UNTR, service du Pr Rondeau, Hôpital Tenon

Paris, Paris Cedex 20, 75020, France

Location

Department of Nephrology, Hemodialysis, Apheresis, and Transplantation, CHUGA (centre hospitalier universitaire Grenoble-Alpes)

Grenoble, France

Location

Centre Hospitalier Régional Universitaire de Lille, Nephrology Service

Lille, 59000, France

Location

Nephrology Service CHU Bichat

Paris, 75018, France

Location

Department of Nephrology and Organ Transplant, CHU Rangueil

Toulouse, 31059, France

Location

Karolinska University Hospital Huddinge

Stockholm, 141 86, Sweden

Location

Department of Nephrology, Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (3)

• 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.

  PMID: 20616173 BACKGROUND

• 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.

  PMID: 29162595 BACKGROUND

• Tyrberg L, Andersson F, Uhlin F, Hellmark T, Segelmark M. Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment. Nephrol Dial Transplant. 2023 Dec 20;39(1):45-54. doi: 10.1093/ndt/gfad132.

  PMID: 37385828 DERIVED

MeSH Terms

Conditions

Rapidly progressive glomerulonephritis with pulmonary hemorrhage

Interventions

Mac-1-like protein, Streptococcus

Results Point of Contact

• Title: Professor Mårten Segelmark
• Organization: Linköping University

marten.segelmark@liu.se

+46 70 287 19 44

Study Officials

• Mårten Segelmark, MD PhD Prof

  Linkoeping University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD and Professor Department of Drug Research, Department of Medical and Health Sciences

Model Details: Open-Label, Single Arm study

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: May 17, 2017
• Study Start: June 16, 2017
• Primary Completion: July 24, 2020
• Study Completion: July 24, 2020
• Last Updated: April 7, 2022
• Results First Posted: April 7, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); AU (1); CZ (1); DK (1); SE (2)