Clinical trial NCT05679401: A Study With Imlifidase in Anti-GBM Disease
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Anti-Glomerular Basement Membrane Disease
Anti-Glomerular Basement Membrane Antibody Disease
Goodpasture Syndrome
Good Pasture Syndrome
Keywords: Anti-GBM
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
First posted: 2023-01-11
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, controlled, randomised, multi-centre trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months
timeFrame: At 6 months after randomisation
Secondary outcomes:
measure: Proportion of patients with functioning kidney at 6 months
timeFrame: At 6 months after randomisation
measure: Time to non-toxic level of anti-GBM antibodies
timeFrame: During the study from screening up to 6 months
measure: Exposure to toxic level of anti-GBM antibodies
timeFrame: From randomisation up to Day 22 and to Day 29 respectively
measure: Renal function as evaluated by eGFR at 3 months
timeFrame: At 3 months after randomisation
measure: Proportion of patients with functioning kidney at 3 months,
timeFrame: At 3 months after randomisation
measure: Proportion of patients experiencing end stage renal disease (ESRD) within 6 months
timeFrame: During the study from randomisation up to 6 months
measure: Proportion of patients experiencing death due to anti-GBM disease within 6 months
timeFrame: During the study from randomisation up to 6 months
measure: Change in urine creatinine clearance (CrCl) from randomisation to 3 and 6 months
timeFrame: At randomisation and at 3 and 6 months
measure: U-albumin/creatinine ratio at 3 and 6 months (24h collection)
timeFrame: At screening and at 3 and 6 months
measure: U-albumin/creatinine ratio at screening and during study (morning urine void)
timeFrame: During the study from screening up to 6 months
measure: Renal function as evaluated by eGFR at screening and during study
timeFrame: During the study from screening up to 6 months
measure: Number of PLEX sessions within 3 months from randomisation
timeFrame: During the study from randomisation up to 3 months
measure: Number of days on dialysis within 3 and 6 months from randomisation
timeFrame: During the study from randomisation to 3 months and 6 months
measure: Proportion of patients being negative during study for anti-GBM antibodies/anti-neutrophilic cytoplasmic autoantibodies (ANCA)/anti-GBM antibodies+ANCA
timeFrame: During the study from screening up to 6 months
measure: Number of days with mechanical ventilation due to anti-GBM disease within 3 months from randomisation
timeFrame: During the study from randomisation to 3 months
measure: Number of days at intensive care unit (ICU) and number of days in hospitalisation from randomisation to 3 months
timeFrame: During the study from randomisation to 3 months
measure: Change in health related quality of life (HRQoL) from screening to 6 months
timeFrame: At screening and at 6 months
measure: Change in health status from screening to 6 months
timeFrame: At screening and at 6 months
measure: Pharmacokinetic (PK) data (Cmax) from start of treatment to Day 15
timeFrame: During the study from before administration of imlifidase up to Day 15
measure: Imlifidase pharmacodynamic (PD) profile (IgG levels in serum) from start of treatment to Day 15
timeFrame: During the study from before administration of imlifidase up to Day 15
measure: Imlifidase pharmacodynamic (PD) profile (composition of different IgG fractions) from start of treatment to Day 15
timeFrame: During the study from before administration of imlifidase up to Day 15
measure: Anti-imlifidase antibody levels from start of imlifidase treatment to 6 months
timeFrame: During the study from before administration of imlifidase up to 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center Plaza
state: California
city: Baltimore
country: United States
facility: John Hopkins Medical Institution
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Health Clinical Research Unit
state: Minnesota
city: Chapel Hill
country: United States
facility: UNC Kidney Center/Division of Nephrology & Hypertension
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Graz
country: Austria
facility: Med Uni Graz / LKH-UNIV Klinikum Graz, Klinische Abteilung fuer Nephrologie
state: Stiermark
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Dept of Internal Medicine IV (Nephrology and Hypertension)
state: Tirol
city: Vienna
country: Austria
facility: Medical University of Vienna, Dept of Medicine III, Division of Nephrology and dialysis
city: Leuven
country: Belgium
facility: UZ Leuven
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
state: Prague
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital, Renal Medicine and Clinical Medicine
state: Region Midtjylland
city: Odense
country: Denmark
facility: Odense University Hospital, Medical Nephrology, Department Y
state: Region Of Southern Denmark
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Nephrology
city: Marseille
country: France
facility: University Hospital of Marseille, Nephrology - Renal transplantation service
state: Bouches-du-Rhône
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil (University Hospital of Strasbourg)
state: Grand Est
city: Lille
country: France
facility: CHU Lille. Nephrology, dialysis transplantation
state: Haus-de-France
city: Paris
country: France
facility: Tenon Hospital, Renal intensive care unit
state: Ile De France
city: Bois-Guillaume
country: France
facility: CHU de Rouen, Department of Nephrology,Transplantation, and Hemodialysis
state: Normandie
city: Bordeaux
country: France
facility: CHU Bordeaux, Hôpital Pellegrin, Service nephrologie, transplantation, dialyse, aphereses
state: Nouvelle-Aquitaine
city: Toulouse
country: France
facility: Hôpital Rangueil, CHU de Toulouse, Department of Nephrology and Organ transplantation
state: Occitanie
city: Nantes
country: France
facility: CHU de Nantes, Hôtel-Dieu, Le service de néphrologie et immunologie clinique
state: Pays De La Loire
city: Grenoble
country: France
facility: CHU Grenoble Alpes - Michallon Hospital, Nephrology, Hemodialysis, Apheresis and Kidney Transplantation
state: Rhône-Alpes
city: Munich
country: Germany
facility: LMU Klinikum, Medical Clinic IV / Department of Nephrology
state: Bavaria
city: Koeln
country: Germany
facility: Uniklinik Koeln-Klinik II fuer Innere Medizin
state: Nordrhein-Westfalen
city: AAchen
country: Germany
facility: Uniklinik RWTH Aachen
state: NRW
city: Dresden
country: Germany
facility: Carl-Gustav-Carus University Hospital, Medizinische Klinik III, Nephrologie
state: Saxony
city: Berlin
country: Germany
facility: Charité Department of Nephrology and Intensive Care
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen - Medizinische Klinik 4
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf, III Department of Medicine and Nephrology
city: Cork
country: Ireland
facility: Department of Renal Medicine, Cork University Hospital
city: Genova
country: Italy
facility: IRCCS Policlinico San Martino University Hospital, Department of Internal Medicine, Division of Nephrology
state: Genova-Liguria
city: Bologna
country: Italy
facility: IRCCS S. Orsola - Malpighi University Hospital - Nephrology, Dialysis and Transplantation Unit (pav 15)
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - SC Nefrologia
city: Leiden
country: Netherlands
facility: Leiden University Medical Center, Department of Nephrology
state: ZH
city: Groningen
country: Netherlands
facility: University Medical Center Groningen, Division of Nephrology
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital, Department of Nephrology
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Department of Medical Sciences, Renal Medicine
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Dept. of Vasculitis
state: Cambridgeshire
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh, Department of Renal Medicine
city: London
country: United Kingdom
facility: University College London, Royal Free Hospital, Department of Renal Medicine
city: London
country: United Kingdom
facility: Hammersmith Hospital, Renal medicine and centre for inflammatory diseases
city: Manchester
country: United Kingdom
facility: Manchester University Hospitals NHS Foundation Trust
Study officials:
affiliation: Hansa Biopharma AB
name: Clinical Operations
role: STUDY_DIRECTOR
References: