REscue of Nephrons with ALe.F02 (RENAL F02)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alentis Therapeutics AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Jun 2025 → ongoing

Decision date (initial)

2023-07-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alentis Therapeutics AG

External identifiers

EU CT number

2022-502184-38-00

WHO UTN

U1111-1286-9095

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

The primary objective of this study is to assess the safety and tolerability of ALE.F02 when administered as a continuous IV infusion in patients with RPGN attributed to AAV.

Secondary objectives 3

1. 1. To assess the ability of ALE.F02 to preserve renal function and eGFR over time in patients diagnosed with RPGN attributed to AAV when added to SOC;
2. 2. To assess the use of glucocorticoids and immunosuppressant concomitant medications in patients diagnosed with RPGN attributed to AAV when ALE.F02 is added to SOC; and
3. 3. To determine the PK properties of ALE.F02 in patients diagnosed with RPGN attributed to AAV.

Conditions and MedDRA coding

Rapidly progressive glomerulonephritis

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Paul Ehrlich Institute

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Are male or female patients ≥18 years of age of any race or ethnicity with a score of <7 on the Clinical Frailty Scale in the 3 months preceding the onset of RPGN attributed to AAV; Note: The PI should assess the Clinical Frailty Scale based on medical history and interview with the patient.
2. 6. Have a weight of ≤130 kg;
3. 2. Must be willing and able to comply with the study requirements and give informed consent for participation in the study;
4. 3. Must be willing to have a renal biopsy procedure performed no later than prior to study drug administration at the Week 6 Visit; alternatively, a historical biopsy performed up to 45 days prior to the initiation of study drug administration is considered acceptable;
5. 4. Have been newly diagnosed with RPGN within 45 days prior to the initiation of study drug treatment, as demonstrated by the following: - Evidence of loss of renal function with an eGFR of ≤50 mL/min/1.73 m2 and ≥10 mL/min/1.73 m2; and - History of proteinuria of any degree AND/OR hematuria that is temporally associated with the presenting episode of illness and supports the diagnosis of RPGN.
6. 5. Are suspected of having RPGN attributed to AAV at Screening based on clinical laboratory diagnostic criteria, including a positive test for an ANCA, ie, anti MPO or anti-PR3;
7. 7. Female patients must not be pregnant or lactating at Screening and 1 of the following conditions must apply: - Is a female of childbearing potential and agrees to use a highly effective method of birth control during their participation in the study and for at least 5 half-lives or a minimum of 30 days after the last dose of study drug, or as recommended in the Summary of Product Characteristics (SmPC) of any authorized AxMP given as part of background SOC therapy, whichever is longer; or - Is a female of nonchildbearing potential.
8. 8. Female patients must agree not to donate ova for 6 months after the last dose of study drug or as recommended in the SmPC of any authorized AxMP given as part of background SOC therapy, whichever is longer;
9. 9. Male patients must agree to use contraception, in the form of either sexual abstinence or a condom, during their participation in the study and for 90 days after the last dose of study drug or as recommended in the SmPC of any authorized AxMP given as part of background SOC therapy, whichever is longer; and
10. 10. Male patients must agree to abstain from sperm donation during their participation in the study and for 90 days after the last dose of study drug or as recommended in the SmPC of any authorized AxMP given as part of background SOC therapy, whichever is longer.
11. 11. Applicable ONLY to Part B: Have been treated with avacopan up to 14 days prior to Screening and initiated avacopan treatment no later than Study Day 1; and
12. 12. Applicable ONLY to Part B: Are being treated with avacopan as per the SmPC and according to local institutional guidelines.

Exclusion criteria 28

1. 1. Have a history of previous RPGN that resolved or ameliorated (ie, the patient had a documented case of RPGN and has suffered a relapse);
2. 7. Have received a course of SOC therapy which exceeds a high-dose prolonged regimen of treatment of ANCA RPGN, such as >3000 mg of IV methylprednisoloneequipotent glucocorticoids, or >1 mg/kg/day of oral glucocorticoids (prednisone equivalent) for >14 days (doses are provided as a guidance for assessment of intensity; patients who received highdose glucocorticoids should be discussed with and approved by the Medical Monitor and the Sponsor);
3. 9. Have participated in an investigational drug or device study and received investigational therapy <30 days or 5 half lives, whichever is the greater, prior to the first dose of study drug. For biological investigational drugs, the exclusionary period may not be <90 days prior to the first dose of study drug;
4. 8. Have poor venous access;
5. 20. Have alveolar haemorrhage with hypoxia defined by an oxygen saturation <85% or that requires the use of invasive or noninvasive ventilatory support;
6. 21. Have undergone dialysis within 7 days prior to Screening;
7. 22. Have undergone therapeutic plasma exchange within 7 days prior to Screening; or
8. 11. Have a diagnosis of systemic lupus erythematosus-AAV overlap syndrome;
9. 12. Have a diagnosis of eosinophilic granulomatosis with polyangiitis;
10. 17. Have not recovered from AEs and/or complications from major surgery prior to the first dose of study drug; Note: The PI should consult with the Medical Monitor and Sponsor to determine if ongoing, significant complications from major surgery are exclusionary.
11. 13. Have evidence of uncontrolled respiratory, cardiac, hepatic, endocrine, central nervous system, or renal disease, unrelated to RPGN or AAV, that the PI believes cannot be readily brought under control, or any other medical condition that in the opinion of the PI renders the patient unsuitable for enrollment and could prevent the successful completion of the study;
12. 14. Have received a live vaccine within 30 days prior to Screening;
13. 15. Have received any vaccine within 7 days of the first dose of study drug other than against influenza or pneumococcal infection;
14. 16. Are employed by the PI or the study site, have direct involvement in the proposed study or other studies under the direction of that PI, or are a family member of the PI or study site personnel;
15. 23. Have known hypersensitivity to the study drug or any of the excipients used in the formulation of the study drug.
16. 18. Have active or known history of alcohol or substance abuse within 1 year prior to Day 1/Randomization or have a positive urine drug screen for drugs of abuse at Screening;
17. 2. Have a positive serology test for anti-glomerular basement membrane antibodies;
18. 19. Have been diagnosed within the preceding 5 years with a malignant neoplastic disease, other than locally invasive cutaneous squamous or basal cell carcinoma;
19. 3. Have evidence of active or latent TB determined by a positive (not indeterminate) QuantiFERON®-TB Gold test (or equivalent). In countries where QuantiFERON®-TB Gold test (or equivalent) is not available, radiological criteria, including chest X-ray or computed tomography scan, may alternatively be used;
20. 4. Have a chronic infection that could be exacerbated by RPGN or SOC therapy for RPGN;
21. 5. Have active hepatitis B, hepatitis C, or HIV infection. Active hepatitis B infection will be determined by hepatitis B surface antigen and antibody to hepatitis B core antigen testing;
22. 6. Have taken any prohibited medications;
23. 24. Applicable ONLY to Part A: Have been treated with or are expected to be treated with avacopan;
24. 25. Applicable ONLY to Part B: Have been treated with avacopan >14 days prior to Screening;
25. 26. Applicable ONLY to Part B: Have known hypersensitivity to avacopan or any of the excipients used in the formulation of avacopan;
26. 27. Applicable ONLY to Part B: Have evidence of hepatic disease (cirrhosis, other liver diseases AND a Child-Pugh Class C) or aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin >3 × the upper limit of normal before Study Day 1;
27. 28. Applicable ONLY to Part B: Have had a white blood cell count <3500/μL, neutrophil count <1500/μL, or lymphocyte count <500/μL before Study Day 1; or
28. 29. Applicable ONLY to Part B: Have an intake of strong cytochrome P450 (CYP) (CYP3A4) inducers and/or inhibitors, if not in line with the latest SmPC of avacopan.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint for this study is the safety and tolerability of ALE.F02 when administered as a continuous IV infusion in patients with RPGN attributed to AAV. Safety endpoints are the following: - All AEs; - All SAEs; - Hematology and clinical chemistry analyte assessments; - Serum lipids; - Antidrug antibodies (ADAs); and - ECGs.

Secondary endpoints 6

1. 1. The key secondary endpoint for this study is the change in mean eGFR from baseline to Week 24/EOT for recipients of ALE.F02 compared to placebo.
2. 2. Change in mean urine protein to creatinine ratio (UPCR) AUC from baseline to Week 24/EOT and Week 52/EOS for recipients of ALE.F02 compared to placebo;
3. 3. Time to stable proteinuria (≤0.5 g/day for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
4. 4. Time to stable hematuria (≤5 RBCs/high-power field for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
5. 5. Incidence of RRT at any time during the study for recipients of ALE.F02 compared to placebo; and
6. 6. Total glucocorticoid and immunosuppressive exposure at Week 24/EOT and Week 52/EOS for recipients of ALE.F02 compared to placebo.

Investigational products

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

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alentis Therapeutics AG

Sponsor organisation

Alentis Therapeutics AG

Address

Hegenheimermattweg 167a

City

Allschwil

Postcode

4123

Country

Switzerland

Scientific contact point

Organisation

Alentis Therapeutics AG

Contact name

Clinical Trial Manager

Public contact point

Organisation

Alentis Therapeutics AG

Contact name

Clinical Trial Manager

Third parties 4

Locations

7 EU/EEA countries · 42 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

Temporary halts 7 · Art. 38 CTR

Results and documents

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

Documents 69 files

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

Application history

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