A Study With Imlifidase in Anti-GBM Disease

NCT ID: NCT05679401

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-22
• Study Completion Date: 2026-11-30

Brief Summary

An open-label, controlled, randomised, multi-centre Phase 3 trial evaluating renal function in patients with severe anti-GBM disease comparing imlifidase and standard of care (SoC) with SoC alone. All patients will remain in the trial for 24 months.

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo screening to determine eligibility for study entry. Patients will be randomised to treatment in a 1:1 ratio to either imlifidase and SoC or SoC only.

SoC consists of a combination of plasma exchange (PLEX), cyclophosphamide (CYC), and glucocorticoids. For patients randomised to the imlifidase arm the first PLEX immediately after randomisation is replaced by administration of imlifidase.

Kidney function, anti-GBM antibody levels, pulmonary symptoms, safety, pharmacokinetic/pharmacodynamic (PK/PD) and health related quality of life (HRQoL) among others, will be assessed.

Conditions

Anti-Glomerular Basement Membrane Disease; Anti-Glomerular Basement Membrane Antibody Disease; Goodpasture Syndrome; Good Pasture Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imlifidase and Standard-of-Care (SoC)

• Imlifidase is administered IV as one dose of 0.50 mg/kg over 30 minutes.
• SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.

Group Type: EXPERIMENTAL

Imlifidase

Intervention Type: DRUG

Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG.

Plasma exchange (PLEX)

Intervention Type: PROCEDURE

PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.

Cyclophosphamide (CYC)

Intervention Type: DRUG

Cyclophosphamide's main mechanism of action (i.e. crosslinking of strands of DNA and RNA) results in inhibition of protein synthesis. Hence treatment prevents formation of new anti-GBM antibodies.

Glucocorticoids

Intervention Type: DRUG

Glucocorticoids inhibit the inflammation process.

Standard-of-Care (SoC)

SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.

Group Type: ACTIVE_COMPARATOR

Plasma exchange (PLEX)

Intervention Type: PROCEDURE

PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.

Cyclophosphamide (CYC)

Intervention Type: DRUG

Cyclophosphamide's main mechanism of action (i.e. crosslinking of strands of DNA and RNA) results in inhibition of protein synthesis. Hence treatment prevents formation of new anti-GBM antibodies.

Glucocorticoids

Intervention Type: DRUG

Glucocorticoids inhibit the inflammation process.

Interventions

Imlifidase

Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG.

Intervention Type: DRUG

Plasma exchange (PLEX)

PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.

Intervention Type: PROCEDURE

Cyclophosphamide (CYC)

Cyclophosphamide's main mechanism of action (i.e. crosslinking of strands of DNA and RNA) results in inhibition of protein synthesis. Hence treatment prevents formation of new anti-GBM antibodies.

Intervention Type: DRUG

Glucocorticoids

Glucocorticoids inhibit the inflammation process.

Intervention Type: DRUG

Other Intervention Names

IdeS, HMED-IdeS; PE

Eligibility Criteria

Inclusion Criteria

1. Anti-GBM antibodies constituting an indication for PLEX as judged by the Investigator

2. Haematuria on dipstick and/or urinary sediment

3. eGFR(MDRD) <20 mL/min/1.73 m^2

4. Patients aged ≥18 years

5. Willing and able to give written Informed Consent and to comply with the requirements of the study protocol

Exclusion Criteria

1. Diagnosis of anti-GBM disease more than 14 days prior to randomisation

2. Anuria during the last 24-hour

3. Any constituent of SoC given more than 10 days prior to randomisation

4. IVIg within 4 weeks before randomisation

5. History or presence of any medical condition or disease which, in the opinion of the investigator, may place the patient at unacceptable risk, or jeopardise the purpose of the study

6. Patients previously randomised in the study

7. Unsuitable to participate in the trial for any other reason in the opinion of the investigator

8. Pregnancy or breast feeding

9. Contraception:

1. Men who are not vasectomised or abstinent or with a partner (of child-bearing potential) not willing to use one of the highly effective contraceptives listed below from screening to 6 months following discontinuation of CYC

2. Men who are not willing to refrain from donating sperm from screening to 6 months following discontinuation of CYC

3. Men who are not willing to use a condom during any form of sexual intercourse, regardless of a partner being of child-bearing potential from screening to 6 months following discontinuation of CYC

4. Women of child-bearing potential not willing or not able to use at least one highly effective contraceptive method from screening to 12 months following discontinuation of CYC.

In the context of this trial, a highly effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:

• combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral/intravaginal/transdermal)
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral/injectable/implantable)
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion
• vasectomised partner
• true abstinence: When this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]

10. Previous imlifidase treatment or known hypersensitivity to any of the excipients

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

Sponsors

Hansa Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Operations

Role: STUDY_DIRECTOR

Hansa Biopharma AB

Locations

UCLA Medical Center Plaza

Los Angeles, California, United States

John Hopkins Medical Institution

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Minnesota Health Clinical Research Unit

Minneapolis, Minnesota, United States

UNC Kidney Center/Division of Nephrology & Hypertension

Chapel Hill, North Carolina, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Med Uni Graz / LKH-UNIV Klinikum Graz, Klinische Abteilung fuer Nephrologie

Graz, Stiermark, Austria

Medical University Innsbruck, Dept of Internal Medicine IV (Nephrology and Hypertension)

Innsbruck, Tyrol, Austria

Medical University of Vienna, Dept of Medicine III, Division of Nephrology and dialysis

Vienna, , Austria

UZ Leuven

Leuven, , Belgium

Všeobecná fakultní nemocnice v Praze

Prague, Prague, Czechia

Aarhus University Hospital, Renal Medicine and Clinical Medicine

Aarhus N, Central Jutland, Denmark

Odense University Hospital, Medical Nephrology, Department Y

Odense, Region Syddanmark, Denmark

Rigshospitalet, Department of Nephrology

Copenhagen, , Denmark

CHU Grenoble Alpes - Michallon Hospital, Nephrology, Hemodialysis, Apheresis and Kidney Transplantation

Grenoble, Auvergne-Rhône-Alpes, France

University Hospital of Marseille, Nephrology - Renal transplantation service

Marseille, Bouches-du-Rhône, France

Nouvel Hôpital Civil (University Hospital of Strasbourg)

Strasbourg, Grand Est, France

CHU Lille. Nephrology, dialysis transplantation

Lille, Haus-de-France, France

CHU de Rouen, Department of Nephrology,Transplantation, and Hemodialysis

Bois-Guillaume, Normandy, France

CHU Bordeaux, Hôpital Pellegrin, Service nephrologie, transplantation, dialyse, aphereses

Bordeaux, Nouvelle-Aquitaine, France

Hôpital Rangueil, CHU de Toulouse, Department of Nephrology and Organ transplantation

Toulouse, Occitanie, France

CHU de Nantes, Hôtel-Dieu, Le service de néphrologie et immunologie clinique

Nantes, Pays de la Loire Region, France

Tenon Hospital, Renal intensive care unit

Paris, Île-de-France Region, France

LMU Klinikum, Medical Clinic IV / Department of Nephrology

Munich, Bavaria, Germany

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, Germany

Uniklinik Koeln-Klinik II fuer Innere Medizin

Cologne, North Rhine-Westphalia, Germany

Carl-Gustav-Carus University Hospital, Medizinische Klinik III, Nephrologie

Dresden, Saxony, Germany

Charité Department of Nephrology and Intensive Care

Berlin, , Germany

Universitaetsklinikum Erlangen - Medizinische Klinik 4

Erlangen, , Germany

University Hospital Hamburg-Eppendorf, III Department of Medicine and Nephrology

Hamburg, , Germany

Department of Renal Medicine, Cork University Hospital

Cork, , Ireland

IRCCS Policlinico San Martino University Hospital, Department of Internal Medicine, Division of Nephrology

Genova, Genova-Liguria, Italy

IRCCS S. Orsola - Malpighi University Hospital - Nephrology, Dialysis and Transplantation Unit (pav 15)

Bologna, , Italy

ASST degli Spedali Civili di Brescia - SC Nefrologia

Brescia, , Italy

Leiden University Medical Center, Department of Nephrology

Leiden, South Holland, Netherlands

University Medical Center Groningen, Division of Nephrology

Groningen, , Netherlands

Radboudumc

Nijmegen, , Netherlands

University Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Karolinska University Hospital

Huddinge, , Sweden

Linköping University Hospital

Linköping, , Sweden

Skåne University Hospital, Department of Nephrology

Lund, , Sweden

Uppsala University Hospital, Department of Medical Sciences, Renal Medicine

Uppsala, , Sweden

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Dept. of Vasculitis

Cambridge, Cambridgeshire, United Kingdom

Royal Infirmary of Edinburgh, Department of Renal Medicine

Edinburgh, , United Kingdom

University College London, Royal Free Hospital, Department of Renal Medicine

London, , United Kingdom

Hammersmith Hospital, Renal medicine and centre for inflammatory diseases

London, , United Kingdom

Manchester University Hospitals NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Austria; Belgium; Czechia; Denmark; France; Germany; Ireland; Italy; Netherlands; Spain; Sweden; United Kingdom

Other Identifiers

2022-500121-33-01

Identifier Type: OTHER

Identifier Source: secondary_id

1005498

Identifier Type: OTHER

Identifier Source: secondary_id

21-HMedIdeS-24

Identifier Type: -

Identifier Source: org_study_id