A Study With Imlifidase in Anti-GBM Disease (GOOD-IDES-02)

A Phase 3 Open-label, Controlled, Randomised, Multi-centre Trial Comparing Imlifidase and Standard-of-care With Standard-of-care Alone in the Treatment of Severe Anti-GBM Antibody Disease (Goodpasture Disease)

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.

Study Overview

• Status: Terminated
• Conditions: Anti-Glomerular Basement Membrane Disease; Goodpasture Syndrome; Anti-Glomerular Basement Membrane Antibody Disease; Good Pasture Syndrome
• Intervention / Treatment: Drug: Imlifidase; Procedure: Plasma exchange (PLEX); Drug: Cyclophosphamide (CYC); Drug: Glucocorticoids

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna, Dept of Medicine III, Division of Nephrology and dialysis
  • Stiermark
    • Graz, Stiermark, Austria, 8036
      • Med Uni Graz / LKH-UNIV Klinikum Graz, Klinische Abteilung fuer Nephrologie
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University Innsbruck, Dept of Internal Medicine IV (Nephrology and Hypertension)
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Czechia
  • Prague
    • Prague, Prague, Czechia, 12808
      • Vseobecna Fakultni Nemocnice V Praze
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet, Department of Nephrology
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Aarhus University Hospital, Renal Medicine and Clinical Medicine
  • Region Syddanmark
    • Odense, Region Syddanmark, Denmark, 5000
      • Odense University Hospital, Medical Nephrology, Department Y
• France
  • Auvergne-Rhône-Alpes
    • Grenoble, Auvergne-Rhône-Alpes, France, 38043
      • CHU Grenoble Alpes - Michallon Hospital, Nephrology, Hemodialysis, Apheresis and Kidney Transplantation
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13385
      • University Hospital of Marseille, Nephrology - Renal transplantation service
  • Grand Est
    • Strasbourg, Grand Est, France, 67091 Cedex
      • Nouvel Hôpital Civil (University Hospital of Strasbourg)
  • Haus-de-France
    • Lille, Haus-de-France, France, 59037
      • CHU Lille. Nephrology, dialysis transplantation
  • Normandy
    • Bois-Guillaume, Normandy, France, 76130
      • CHU de Rouen, Department of Nephrology,Transplantation, and Hemodialysis
  • Nouvelle-Aquitaine
    • Bordeaux, Nouvelle-Aquitaine, France, 33076 cedex
      • CHU Bordeaux, Hôpital Pellegrin, Service nephrologie, transplantation, dialyse, aphereses
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • Hôpital Rangueil, CHU de Toulouse, Department of Nephrology and Organ transplantation
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44000
      • CHU de Nantes, Hôtel-Dieu, Le service de néphrologie et immunologie clinique
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75020
      • Tenon Hospital, Renal intensive care unit
• Germany
  • Berlin, Germany, 10117
    • Charité Department of Nephrology and Intensive Care
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen - Medizinische Klinik 4
  • Hamburg, Germany, 20246
    • University Hospital Hamburg-Eppendorf, III Department of Medicine and Nephrology
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • LMU Klinikum, Medical Clinic IV / Department of Nephrology
  • North Rhine-Westphalia
    • Aachen, North Rhine-Westphalia, Germany, 52074
      • Uniklinik RWTH Aachen
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Uniklinik Koeln-Klinik II fuer Innere Medizin
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Carl-Gustav-Carus University Hospital, Medizinische Klinik III, Nephrologie
• Ireland
  • Cork, Ireland, T12 DC4A
    • Department of Renal Medicine, Cork University Hospital
• Italy
  • Bologna, Italy, 40138
    • IRCCS S. Orsola - Malpighi University Hospital - Nephrology, Dialysis and Transplantation Unit (pav 15)
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia - SC Nefrologia
  • Genova-Liguria
    • Genova, Genova-Liguria, Italy, 16132
      • IRCCS Policlinico San Martino University Hospital, Department of Internal Medicine, Division of Nephrology
• Netherlands
  • Groningen, Netherlands, 9713GZ
    • University Medical Center Groningen, Division of Nephrology
  • Nijmegen, Netherlands, 6525 GA
    • Radboudumc
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Leiden University Medical Center, Department of Nephrology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • University Hospital Vall d'Hebron
• Sweden
  • Huddinge, Sweden, 14186
    • Karolinska University Hospital
  • Linköping, Sweden, 58185
    • Linköping University Hospital
  • Lund, Sweden, 22185
    • Skåne University Hospital, Department of Nephrology
  • Uppsala, Sweden, 751 85
    • Uppsala University Hospital, Department of Medical Sciences, Renal Medicine
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh, Department of Renal Medicine
  • London, United Kingdom, NW3 2QG
    • University College London, Royal Free Hospital, Department of Renal Medicine
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital, Renal medicine and centre for inflammatory diseases
  • Manchester, United Kingdom, M13 9WL
    • Manchester University Hospitals NHS Foundation Trust
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Dept. of Vasculitis
• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Medical Center Plaza
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins Medical Institution
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Health Clinical Research Unit
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7155
      • UNC Kidney Center/Division of Nephrology & Hypertension
  • Ohio
    • Columbus, Ohio, United States, 43201
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard-of-Care (SoC); SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.	Procedure: Plasma exchange (PLEX); PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.; Other Names: PE; Drug: 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.; Drug: Glucocorticoids; Glucocorticoids inhibit the inflammation process.
Experimental: 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.	Drug: 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.; Other Names: IdeS, HMED-IdeS; Procedure: Plasma exchange (PLEX); PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.; Other Names: PE; Drug: 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.; Drug: Glucocorticoids; Glucocorticoids inhibit the inflammation process.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months	At 6 months after randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Exposure to anti-GBM antibodies will be assessed by evaluation of the area under the anti-GBM antibody concentration versus time curve.	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
Proportion of patients experiencing end stage renal disease (ESRD) within 6 months		During the study from randomisation up to 6 months
Proportion of patients experiencing death due to anti-GBM disease within 6 months		During the study from randomisation up to 6 months
Change in urine creatinine clearance (CrCl) from randomisation to 3 and 6 months		At randomisation and at 3 and 6 months
U-albumin/creatinine ratio at 3 and 6 months (24h collection)		At screening and at 3 and 6 months
U-albumin/creatinine ratio at screening and during study (morning urine void)		During the study from screening up to 6 months
Renal function as evaluated by eGFR at screening and during study		During the study from screening up to 6 months
Number of PLEX sessions within 3 months from randomisation		During the study from randomisation up to 3 months
Number of days on dialysis within 3 and 6 months from randomisation		During the study from randomisation to 3 months and 6 months
Proportion of patients being negative during study for anti-GBM antibodies/anti-neutrophilic cytoplasmic autoantibodies (ANCA)/anti-GBM antibodies+ANCA		During the study from screening up to 6 months
Number of days with mechanical ventilation due to anti-GBM disease within 3 months from randomisation		During the study from randomisation to 3 months
Number of days at intensive care unit (ICU) and number of days in hospitalisation from randomisation to 3 months		During the study from randomisation to 3 months
Change in health related quality of life (HRQoL) from screening to 6 months	All patients will fill out the HRQoL questionnaire PROMIS-29 which is a universal rather than disease specific measure. The PROMIS-29 measure assesses pain intensity using a single 0-10 numeric pain rating item and seven health domains using four items each: physical functioning, fatigue, pain interference, depression, anxiety, ability to participate in social roles and activities, and sleep disturbance. The score of each domain is converted into a standardized score so called T-score reported for each patient. A T-score of 50 represent a person from a reference population. A T-score higher than 50 indicates more of what is measured and a T-score less than 50 indicates less of what is measured.	At screening and at 6 months
Change in health status from screening to 6 months	All patients will fill out the EQ-5D-5L questionnarie that comprises 5 questions measuring 5 dimensions of health status (mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression). Patients will be asked to select a response to each category that best describes their current health. The EQ-5D-5L also contains a visual analogue scale and the patients will be asked to rate their health on a scale of 0-100.	At screening and at 6 months
Pharmacokinetic (PK) data (Cmax) from start of treatment to Day 15	Cmax = Maximum observed plasma concentration of imlifidase following dosing.	During the study from before administration of imlifidase up to Day 15
Imlifidase pharmacodynamic (PD) profile (IgG levels in serum) from start of treatment to Day 15	Imlifidase cleaves IgG. PD of imlifidase will be assessed as IgG levels in serum. A validated electrochemiluminescence (ECL) method will be used for the analysis.	During the study from before administration of imlifidase up to Day 15
Imlifidase pharmacodynamic (PD) profile (composition of different IgG fractions) from start of treatment to Day 15	Imlifidase cleaves IgG. PD of imlifidase will be assessed using a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis to measure the composition of the following fractions of IgG: Intact IgG, single cleaved IgG (scIgG) and Fab'2 fraction.	During the study from before administration of imlifidase up to Day 15
Anti-imlifidase antibody levels from start of imlifidase treatment to 6 months	Only applicable for patients who receive imlifidase.	During the study from before administration of imlifidase up to 6 months

Collaborators and Investigators

• Sponsor: Hansa Biopharma AB
• Investigators: Study Director: Clinical Operations, Hansa Biopharma AB

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): June 23, 2025
• Study Completion (Actual): February 2, 2026

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 23, 2022
• First Posted (Actual): January 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Anti-GBM
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Glomerulonephritis; Nephritis; Anti-Glomerular Basement Membrane Disease; Rapidly progressive glomerulonephritis with pulmonary hemorrhage; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Therapeutics; Surgical Procedures, Operative; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Biological Therapy; Blood Component Removal; Adrenal Cortex Hormones; Blood Transfusion; Plasmapheresis; Sorption Detoxification; Extracorporeal Circulation; Cyclophosphamide; Glucocorticoids; Plasma Exchange; Mac-1-like protein, Streptococcus
• Other Study ID Numbers: 21-HMedIdeS-24; 2022-500121-33-01 (Other Identifier: EU Trial Number); 1005498 (Other Identifier: Integrated Research Application System (IRAS), UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No