A Study With Imlifidase in Anti-GBM Disease

NCT05679401 | Terminated Phase 3 DMC FDA Drug

• 3 other identifiers: 21-HMedIdeS-242022-500121-33-011005498
• Study Type: interventional
• Target: 50
• Locations: 13 countries
• Sites: 48

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.

Conditions

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

Keywords

Anti-GBM

Outcome Measures

Primary Outcomes (1)

• Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months

  At 6 months after randomisation

Secondary Outcomes (22)

• Proportion of patients with functioning kidney at 6 months

  At 6 months after randomisation

• Time to non-toxic level of anti-GBM antibodies

  During the study from screening up to 6 months

• Exposure to toxic level of anti-GBM antibodies

  From randomisation up to Day 22 and to Day 29 respectively

• Renal function as evaluated by eGFR at 3 months

  At 3 months after randomisation

• Proportion of patients with functioning kidney at 3 months,

  At 3 months after randomisation

Study Arms (2)

Imlifidase and Standard-of-Care (SoC)

EXPERIMENTAL

* 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.

Drug: Imlifidase; Procedure: Plasma exchange (PLEX); Drug: Cyclophosphamide (CYC); Drug: Glucocorticoids

Standard-of-Care (SoC)

ACTIVE COMPARATOR

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

Procedure: Plasma exchange (PLEX); Drug: Cyclophosphamide (CYC); Drug: Glucocorticoids

Interventions

Plasma exchange (PLEX) PROCEDURE

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

Also known as: PE

Imlifidase and Standard-of-Care (SoC); Standard-of-Care (SoC)

Cyclophosphamide (CYC) 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.

Imlifidase and Standard-of-Care (SoC); Standard-of-Care (SoC)

Glucocorticoids DRUG

Glucocorticoids inhibit the inflammation process.

Imlifidase and Standard-of-Care (SoC); Standard-of-Care (SoC)

Imlifidase 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.

Also known as: IdeS, HMED-IdeS

Imlifidase and Standard-of-Care (SoC)

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 constituting an indication for PLEX as judged by the Investigator
• Haematuria on dipstick and/or urinary sediment
• eGFR(MDRD) \<20 mL/min/1.73 m\^2
• Patients aged ≥18 years
• Willing and able to give written Informed Consent and to comply with the requirements of the study protocol

You may not qualify if:

• Diagnosis of anti-GBM disease more than 14 days prior to randomisation
• Anuria during the last 24-hour
• Any constituent of SoC given more than 10 days prior to randomisation
• IVIg within 4 weeks before randomisation
• 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
• Patients previously randomised in the study
• Unsuitable to participate in the trial for any other reason in the opinion of the investigator
• Pregnancy or breast feeding
• Contraception:
• 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
• Men who are not willing to refrain from donating sperm from screening to 6 months following discontinuation of CYC
• 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
• 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)

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (48)

UCLA Medical Center Plaza

Los Angeles, California, 90024, United States

Location

John Hopkins Medical Institution

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Health Clinical Research Unit

Minneapolis, Minnesota, 55455, United States

Location

UNC Kidney Center/Division of Nephrology & Hypertension

Chapel Hill, North Carolina, 27599-7155, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43201, United States

Location

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

Graz, Stiermark, 8036, Austria

Location

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

Innsbruck, Tyrol, 6020, Austria

Location

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

Vienna, 1090, Austria

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Všeobecná fakultní nemocnice v Praze

Prague, Prague, 12808, Czechia

Location

Aarhus University Hospital, Renal Medicine and Clinical Medicine

Aarhus N, Central Jutland, 8200, Denmark

Location

Odense University Hospital, Medical Nephrology, Department Y

Odense, Region Syddanmark, 5000, Denmark

Location

Rigshospitalet, Department of Nephrology

Copenhagen, 2100, Denmark

Location

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

Grenoble, Auvergne-Rhône-Alpes, 38043, France

Location

University Hospital of Marseille, Nephrology - Renal transplantation service

Marseille, Bouches-du-Rhône, 13385, France

Location

Nouvel Hôpital Civil (University Hospital of Strasbourg)

Strasbourg, Grand Est, 67091 Cedex, France

Location

CHU Lille. Nephrology, dialysis transplantation

Lille, Haus-de-France, 59037, France

Location

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

Bois-Guillaume, Normandy, 76130, France

Location

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

Bordeaux, Nouvelle-Aquitaine, 33076 cedex, France

Location

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

Toulouse, Occitanie, 31059, France

Location

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

Nantes, Pays de la Loire Region, 44000, France

Location

Tenon Hospital, Renal intensive care unit

Paris, Île-de-France Region, 75020, France

Location

LMU Klinikum, Medical Clinic IV / Department of Nephrology

Munich, Bavaria, 81377, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Uniklinik Koeln-Klinik II fuer Innere Medizin

Cologne, North Rhine-Westphalia, 50937, Germany

Location

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

Dresden, Saxony, 01307, Germany

Location

Charité Department of Nephrology and Intensive Care

Berlin, 10117, Germany

Location

Universitaetsklinikum Erlangen - Medizinische Klinik 4

Erlangen, 91054, Germany

Location

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

Hamburg, 20246, Germany

Location

Department of Renal Medicine, Cork University Hospital

Cork, T12 DC4A, Ireland

Location

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

Genova, Genova-Liguria, 16132, Italy

Location

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

Bologna, 40138, Italy

Location

ASST degli Spedali Civili di Brescia - SC Nefrologia

Brescia, 25123, Italy

Location

Leiden University Medical Center, Department of Nephrology

Leiden, South Holland, 2333, Netherlands

Location

University Medical Center Groningen, Division of Nephrology

Groningen, 9713GZ, Netherlands

Location

Radboudumc

Nijmegen, 6525 GA, Netherlands

Location

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Karolinska University Hospital

Huddinge, 14186, Sweden

Location

Linköping University Hospital

Linköping, 58185, Sweden

Location

Skåne University Hospital, Department of Nephrology

Lund, 22185, Sweden

Location

Uppsala University Hospital, Department of Medical Sciences, Renal Medicine

Uppsala, 751 85, Sweden

Location

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

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Royal Infirmary of Edinburgh, Department of Renal Medicine

Edinburgh, EH16 4SA, United Kingdom

Location

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

London, NW3 2QG, United Kingdom

Location

Hammersmith Hospital, Renal medicine and centre for inflammatory diseases

London, W12 0HS, United Kingdom

Location

Manchester University Hospitals NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Anti-Glomerular Basement Membrane Disease; Rapidly progressive glomerulonephritis with pulmonary hemorrhage

Interventions

Mac-1-like protein, Streptococcus; Plasma Exchange; Cyclophosphamide; Glucocorticoids

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Clinical Operations

  Hansa Biopharma AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, controlled, randomised, multi-centre trial

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 11, 2023
• Study Start: December 22, 2022
• Primary Completion: June 23, 2025
• Study Completion: February 2, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); IE (1); CZ (1); AU (3); SE (4); IT (3); DK (3); FR (9); NL (3); ES (2); DE (7); BE (1); GB (5)