Company decision, not due to any safety reason.

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.

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.

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