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

NCT ID: NCT03157037

Last Updated: 2022-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-16
• Study Completion Date: 2020-07-24

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.

Conditions

Anti-Glomerular Basement Membrane Antibody Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imlifidase

Imlifidase 0.25 mg/kg body weight intravenous infusion

Group Type: EXPERIMENTAL

Imlifidase

Intervention Type: BIOLOGICAL

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

Interventions

Imlifidase

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Immunoglobulin G-degrading enzyme of Streptococcus pyogenes; HMed-IdeS; IdeS

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hansa Biopharma AB

INDUSTRY

Sponsor Role: collaborator

Mårten Segelmark

OTHER_GOV

Sponsor Role: lead

Responsible Party

Mårten Segelmark

MD, PhD and Professor Department of Drug Research, Department of Medical and Health Sciences

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mårten Segelmark, MD PhD Prof

Role: PRINCIPAL_INVESTIGATOR

Linkoeping University

Locations

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

PH USI UNTR, service du Pr Rondeau, Hôpital Tenon

Paris, Paris Cedex 20, France

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

Grenoble, , France

Centre Hospitalier Régional Universitaire de Lille, Nephrology Service

Lille, , France

Nephrology Service CHU Bichat

Paris, , France

Department of Nephrology and Organ Transplant, CHU Rangueil

Toulouse, , France

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Department of Nephrology, Uppsala University Hospital

Uppsala, , Sweden

Countries

Austria; Czechia; Denmark; France; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 20616173 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29162595 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37385828 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GOOD-IDES-01

Identifier Type: -

Identifier Source: org_study_id