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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hansa Biopharma AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

8 May 2023 → 3 Feb 2026

Decision date (initial)

2023-09-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Hansa Biopharma AB

External identifiers

EU CT number

2022-500121-33-01

ClinicalTrials.gov

NCT05679401

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

Show superior effect of imlifidase and SoC versus SoC alone on kidney function

Secondary objectives 11

1. Compare renal function between treatment arms
2. Compare time to non-toxic level of anti-GBM antibodies between treatment arms
3. Compare the need for PLEX within 3 months between treatment arms
4. Compare the need for mechanical ventilation within 3 months between treatment arms
5. Compare presence of anti-GBM antibodies and ANCA between treatment arms
6. Compare longitudinal change in health-related quality of life (HRQoL) and health status between treatment arms
7. Assessment of pharmacokinetics (PK) of imlifidase
8. Assessment of pharmacodynamics (PD) (IgG) of imlifidase
9. Assessment of immunogenicity profile of imlifidase
10. Assessment of safety and tolerability of imlifidase
11. Assessment of long-term outcome in terms of kidney and patient survival and recurrence of anti-GBM disease

Conditions and MedDRA coding

Anti-GBM antibody disease (Goodpasture disease)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. An anti-GBM antibody level which: • at last available assessment result is above a toxic level • constitutes an indication for intensive PLEX
2. Haematuria on dipstick and/or urinary sediment
3. eGFR(MDRD) <20 mL/min/1.73 m2
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 11

1. Diagnosis of anti-GBM disease more than 10 days prior to randomisation
2. Contraception: a) 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 b) Men who are not willing to refrain from donating sperm from screening to 6 months following discontinuation of CYC c) 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 d) 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]
3. Previous imlifidase treatment or known hypersensitivity to any of the excipients
4. Anuria for more than 24 hours at time of randomisation (Anuria is defined as < 100 mL urine produced during 24-hours)
5. Any constituent of SoC (PLEX, glucocorticoids or immunosuppressive) given for treatment of rapidly progressing glomerulonephritis and/or pulmonary haemorrhage more than 7 days prior to randomisation
6. IVIg within 4 weeks before randomisation
7. History or presence of any medical condition or disease which, in the opinion of the investigator, may place the patient at unacceptable risk, or would jeopardise the interpretation of the imlifidase results due to severeness of the co-morbidity
8. Patients previously randomised in the study
9. Unsuitable to participate in the trial for any other reason in the opinion of the investigator
10. Pregnancy or breast feeding
11. Start of PLEX more than 3 days prior to the day of randomisation if eGFR when starting PLEX was <20 mL/min/1.73 m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Renal function as evaluated by eGFR at 6 months

Secondary endpoints 19

1. Proportion of patients with functioning kidney at 6 months, i.e. no dialysis events within 4 weeks prior to assessment
2. Time to non-toxic level of anti-GBM antibodies
3. Exposure to toxic level of anti-GBM antibodies
4. Renal function as evaluated by eGFR at 3 months
5. Proportion of patients with functioning kidney at 3 months, i.e. no dialysis event within 4 weeks prior to assessment
6. Proportion of patients experiencing ESRD or death due to anti-GBM disease within 6 months
7. Urine creatinine clearance from randomisation to 3 and 6 months
8. U-albumin at 3 and 6 months (24h collection)
9. U-albumin/creatinine ratio at screening and during study (morning urine void)
10. Renal function as evaluated by eGFR at screening and during study
11. Number of PLEX sessions within 3 months from randomisation
12. Number of days on dialysis within 3 and 6 months from randomisation
13. Proportion of patients being negative during study for: Anti-GBM antibodies; ANCA;Anti-GBM antibodies and ANCA
14. Number of days with mechanical ventilation due to anti-GBM disease within 3 months from randomisation
15. Number of days at ICU and number of days in hospitalisation from randomisation to 3 months
16. HRQoL and health status as evaluated by PROMIS-29 and EQ-5D-5L from screening to 6 months
17. Imlifidase PK data from start of imlifidase treatment to Day 15
18. Imlifidase PD (IgG) profile from start of imlifidase treatment to Day 15
19. Anti-imlifidase antibody levels from start of imlifidase treatment to 6 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hansa Biopharma AB

Sponsor organisation

Hansa Biopharma AB

Address

P.O. Box 785

City

Lund

Postcode

220 07

Country

Sweden

Scientific contact point

Organisation

Hansa Biopharma AB

Contact name

Clinical contact information

Public contact point

Organisation

Hansa Biopharma AB

Contact name

Clinical contact information

Third parties 13

Locations

12 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 135 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

22 submissions — initial application plus substantial / non-substantial modifications