A Study With Imlifidase in Anti-GBM Disease

Phase 3

Active, not recruiting

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

• Registration Number: NCT05679401
• Lead Sponsor: Hansa Biopharma AB

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.

Study Timeline

• Study First Submitted: 2022-12-15
• Study Start: 2022-12-22
• Study First Submitted QC: 2022-12-23
• Study First Posted: 2023-01-11
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Primary Completion: 2025-06
• Study Completion: 2026-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imlifidase and Standard-of-Care (SoC)	Glucocorticoids	* 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.
Standard-of-Care (SoC)	Plasma exchange (PLEX)	SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
Standard-of-Care (SoC)	Cyclophosphamide (CYC)	SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
Imlifidase and Standard-of-Care (SoC)	Cyclophosphamide (CYC)	* 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.
Imlifidase and Standard-of-Care (SoC)	Plasma exchange (PLEX)	* 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.
Standard-of-Care (SoC)	Glucocorticoids	SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
Imlifidase and Standard-of-Care (SoC)	Imlifidase	* 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.

Primary Outcome Measures

Name	Time	Method
Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months	At 6 months after randomisation

Secondary Outcome Measures

Name	Time	Method
Proportion of patients with functioning kidney at 6 months	At 6 months after randomisation
Exposure to toxic level of anti-GBM antibodies	From randomisation up to Day 22 and to Day 29 respectively	Exposure to anti-GBM antibodies will be assessed by evaluation of the area under the anti-GBM antibody concentration versus time curve.
Time to non-toxic level of anti-GBM antibodies	During the study from screening up to 6 months
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 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
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
Change in health related quality of life (HRQoL) from screening to 6 months	At screening and at 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.
Change in health status from screening to 6 months	At screening and at 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.
Pharmacokinetic (PK) data (Cmax) from start of treatment to Day 15	During the study from before administration of imlifidase up to Day 15	Cmax = Maximum observed plasma concentration of imlifidase following dosing.
Imlifidase pharmacodynamic (PD) profile (IgG levels in serum) from start of treatment to Day 15	During the study from before administration of imlifidase up 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.
Imlifidase pharmacodynamic (PD) profile (composition of different IgG fractions) from start of treatment to Day 15	During the study from before administration of imlifidase up 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.
Anti-imlifidase antibody levels from start of imlifidase treatment to 6 months	During the study from before administration of imlifidase up to 6 months	Only applicable for patients who receive imlifidase.

Trial Locations

Locations (48)

Uppsala University Hospital, Department of Medical Sciences, Renal Medicine; 🇸🇪 Uppsala, Sweden

Karolinska University Hospital; 🇸🇪 Huddinge, Sweden

Linköping University Hospital; 🇸🇪 Linköping, Sweden

Skåne University Hospital, Department of Nephrology; 🇸🇪 Lund, Sweden

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

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

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, Tirol, 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; 🇨🇿 Praha 2, Prague, Czechia

Aarhus University Hospital, Renal Medicine and Clinical Medicine; 🇩🇰 Aarhus N, Region Midtjylland, Denmark

Odense University Hospital, Medical Nephrology, Department Y; 🇩🇰 Odense, Region Of Southern Denmark, Denmark

University Hospital of Marseille, Nephrology - Renal transplantation service; 🇫🇷 Marseille, Bouches-du-Rhône, France

Nouvel Hôpital Civil (University Hospital of Strasbourg); 🇫🇷 Strasbourg, Grand Est, France

Rigshospitalet, Department of Nephrology; 🇩🇰 Copenhagen, Denmark

CHU Lille. Nephrology, dialysis transplantation; 🇫🇷 Lille, Haus-de-France, France

Tenon Hospital, Renal intensive care unit; 🇫🇷 Paris, Ile De France, France

CHU de Rouen, Department of Nephrology,Transplantation, and Hemodialysis; 🇫🇷 Bois-Guillaume, Normandie, 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, France

CHU Grenoble Alpes - Michallon Hospital, Nephrology, Hemodialysis, Apheresis and Kidney Transplantation; 🇫🇷 Grenoble, Rhône-Alpes, France

LMU Klinikum, Medical Clinic IV / Department of Nephrology; 🇩🇪 Munich, Bavaria, Germany

Uniklinik Koeln-Klinik II fuer Innere Medizin; 🇩🇪 Koeln, Nordrhein-Westfalen, Germany

Uniklinik RWTH Aachen; 🇩🇪 AAchen, NRW, 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, ZH, Netherlands

University Medical Center Groningen, Division of Nephrology; 🇳🇱 Groningen, Netherlands

Radboudumc; 🇳🇱 Nijmegen, Netherlands

University Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

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