Rescue of Nephrons With ALE.F02 (RENAL-F02)
RENAL-F02
A Randomized, Double-Blind, Placebo-Controlled Study of Intravenously Administered ALE.F02 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Renal Sparing in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Rapidly Progressive Glomerulonephritis
3 other identifiers
interventional
80
10 countries
49
Brief Summary
The goal of this clinical trial is to learn if a new drug that might help protect and preserve kidney function in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). AAV is a type of autoimmune disease where the body's own immune system attacks itself, and in the case of AAV the body attacks its own small blood vessels. There are many small blood vessels in the kidneys meaning the kidneys are commonly affected in AAV. The main questions it aims to answer are:
- Is the new drug well tolerated and safe?
- Can the new drug protect and preserve kidney functions when is added to standard therapy? Researchers will compare the following groups to see how the new drug is tolerated and what effect to preserve kidney tissue has:
- Group A: Standard treatment + ALE.F02 low dose infusions
- Group B: Standard treatment + ALE.F02 high dose infusions
- Group C: Standard treatment + ALE.F02 maximum dose infusions
- Group D: Standard treatment + placebo infusions (inactive substance) The Treatment period will consist of 24 weeks beginning on Day 1, during which time participants will receive 13 infusions of the study medicine, along with standard therapy for kidney inflammation due to AAV. During the treatment period, participants will have the following assessments:
- A brief physical examination focusing on their skin any pre-existing medical conditions that you have.
- Collection of blood and urine samples for routine safety tests and to assess renal function.
- Collection of blood samples:
- To measure the amount of study medicine in their blood. This is called pharmacokinetics (PK) and it is tested to see how study medicine enters, moves through, and exits the body.
- To test for antidrug antibodies (ADA). To check if their body create antibodies against the study medicine, as this could reduce its effect.
- To measure biomarkers. Biomarkers are specific compounds in the body (can be protein, hormones, or genetic molecules) that indicate normal or abnormal processes taking place in your body and may be a sign of an underlying condition or disease (for example glucose levels are used as biomarker in managing diabetes). They are used to see how well the body responds to a treatment for a disease or condition.
- Collection of urine to measure urine markers of vasculitis/inflammation called biomarkers.
- Urine pregnancy test. A urine pregnancy test is a quick medical test that can tell if a woman is pregnant or not by checking for a hormone which is produced during pregnancy, usually in the urine.
- Chest High Resolution Computed Tomography (HRCT) scan to check whether they have vasculitis affecting their lungs. A CT scan uses special x-ray equipment to take detailed pictures of body tissues and organs to diagnose and monitor conditions in various parts of the body. For the CT scan, they will need to lie still on a table. At Week 24 a second lung CT scan will be performed for participants whose initial scan showed lung vasculitis to see whether your lung vasculitis is getting better or ongoing/worse.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2023
Typical duration for phase_2
49 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 5, 2023
CompletedStudy Start
First participant enrolled
September 7, 2023
CompletedFirst Posted
Study publicly available on registry
September 21, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
November 20, 2025
November 1, 2025
3.8 years
September 5, 2023
November 19, 2025
Conditions
Outcome Measures
Primary Outcomes (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 rapidly progressive glomerulonephritis (RPGN) attributed to AAV.
Safety endpoints are the following: * All adverse events (AEs); * All serious adverse events (SAEs); * Hematology and clinical chemistry analyte assessments; * Serum lipids; * Antidrug antibodies (ADAs); and * ECGs
through study completion, an average of 1 year
Secondary Outcomes (7)
The key secondary endpoint for this study is the change in mean estimated glomerular filtration rate (eGFR) from baseline to Week 24/End of Treatment (EOT) for recipients of ALE.F02 compared to placebo.
from baseline to Week 24/EOT
Change in mean urine protein to creatinine ratio (UPCR) area under the concentration time curve (AUC) from baseline to Week 24/EOT for recipients of ALE.F02 compared to placebo;
from baseline to Week 24/EOT
Change in mean urine protein to creatinine ratio (UPCR) area under the concentration time curve (AUC) from baseline to Week 52/End of Study (EOS) for recipients of ALE.F02 compared to placebo;
from baseline to Week 52/EOS
Time to stable proteinuria (≤0.5 g/day for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
up to 24 weeks
Time to stable hematuria (≤5 RBCs/high-power field for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
up to 24 weeks
- +2 more secondary outcomes
Study Arms (4)
Standard treatment + ALE.F02 low dose infusions
EXPERIMENTALStandard treatment + ALE.F02 low dose infusions
Standard treatment + ALE.F02 high dose infusions
EXPERIMENTALStandard treatment + ALE.F02 high dose infusions
Standard treatment + placebo infusions (inactive substance)
PLACEBO COMPARATORStandard treatment + placebo infusions (inactive substance)
Standard treatment + ALE.F02 maximum dose infusions
EXPERIMENTALStandard treatment + ALE.F02 maximum dose infusions
Interventions
ALE.F02 is an anti-Claudin-1 (CLDN1) monoclonal antibody (mAb) to selectively target the non-tight junctions (TJ), exposed form of CLDN1. CLDN1 is an integral component of the TJs between cells.
Rituximab is a monoclonal antibody that targets cluster of differentiation antigen 20 (CD20), an antigen expressed on the surface of pre-B and mature B-lymphocytes
Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones that bind to the glucocorticoid receptor. Glucocorticoid effects may be broadly classified into two major categories: immunological and metabolic.
Cyclophosphamid is a medication used as chemotherapy and to suppress the immune system
Drug product that will contain no active ingredient
Immunosuppressants are drugs that prevent your immune system from attacking healthy cells and tissues by mistake.
Eligibility Criteria
You may qualify if:
- 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
- Must be willing and able to comply with the study requirements and give informed consent for participation in the study;
- 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;
- 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. Note: The hematuria may be represented by the presence of eumorphic or dysmorphic red blood cells (RBCs) and/or RBC casts. Patients with extrarenal manifestations of ANCA which started prior to RPGN should be discussed with the Medical Monitor and the Sponsor.
- 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-myeloperoxidase (MPO) or anti-proteinase 3 (PR3);
- Have a body weight of ≤130 kg;
- 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 standard of care (SOC) therapy, whichever is longer; or - Is a female of nonchildbearing potential.
- 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;
- 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 auxiliary medicinal product (AxMP) given as part of background SOC therapy, whichever is longer; and
- 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.
You may not qualify if:
- Have a history of previous RPGN that resolved or ameliorated (ie, the patient had a documented case of RPGN and has suffered a relapse);
- Have a positive serology test for anti-glomerular basement membrane antibodies;
- Have evidence of active or latent tuberculosis (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;
- Have a chronic infection that could be exacerbated by RPGN or SOC therapy for RPGN;
- Have active hepatitis B, hepatitis C, or HIV infection;
- Have taken any prohibited medications.
- Have been treated or planned to be treated with avacopan;
- Have poor venous access;
- Have a diagnosis of systemic lupus erythematosus-AAV overlap syndrome;
- Have a diagnosis of eosinophilic granulomatosis with polyangiitis;
- 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;
- Have received a live vaccine within 30 days prior to Screening;
- Have received any vaccine within 7 days of the first dose of study drug other than against influenza or pneumococcal infection;
- 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;
- 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;
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (49)
Vseobecna fakultni nemocnice v Praze
Prague, 128 08, Czechia
Institut klinicke a experimentalni mediciny
Prague, 140 21, Czechia
Aalborg University Hospital
Aalborg, 9000, Denmark
Aarhus University Hospital
Aarhus, 8200, Denmark
Rigshospitalet
Copenhagen, 56 2100, Denmark
Odense University Hospital
Odense, 5000, Denmark
Centre Hospitalier Boulogne sur Mer
Boulogne-sur-Mer, Cedex, 62200, France
CHU Bordeaux - Hopital Pellegrin
Bordeaux, 33000, France
CHRU de Brest - Hopital de la Cavale Blanche
Brest, 29200, France
CHU Grenoble-Alpes - Hopital Michallon
La Tronche, 38700, France
CHU de Nantes - Hotel-Dieu
Nantes, 44000, France
CHU de Nimes
Nîmes, 31000, France
AP-HP Hopital Pitie-Salpetriere
Paris, 75013, France
AP-HP Hopital Cochin
Paris, 75014, France
CHU de Toulouse - Hopital Rangueil
Toulouse, 31400, France
Centre Hospitalier de Valenciennes
Valenciennes, 59300, France
Charite Universitaetsmedizin Berlin
Berlin, 10117, Germany
Universitaetsklinikum Koeln (AoeR)
Cologne, 50931, Germany
Universitaetsklinikum Carl Gustav Carus Dresden
Dresden, 01307, Germany
Universitaetsklinikum Essen
Essen, 45147, Germany
Medizinische Hochschule Hannover (MHH)
Hanover, 30625, Germany
Universitaetsklinikum Leipzig
Leipzig, 04103, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
Lübeck, 23562, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
München, 80802, Germany
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Bergamo, 24127, Italy
Azienda Ospedaliero-Universitaria Careggi
Florence, 50134, Italy
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Rome, 00168, Italy
APSS Ospedale Santa Chiara di Trento
Trento, 38122, Italy
Fundacio Puigvert
Barcelona, 08025, Spain
Hospital Universitari de Bellvitge
Barcelona, 08907, Spain
Hospital Universitari Arnau de Vilanova
Lleida, 25198, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Regional Universitario de Malaga
Málaga, 29001, Spain
Linkoping University Hospital
Linköping, 581 85, Sweden
University Hospital of Umea
Umeå, 907 37, Sweden
Kantonsspital Baden AG
Baden, 5404, Switzerland
Inselspital, Universitaetsspital Bern
Bern, 3010, Switzerland
Kantonsspital St. Gallen
Sankt Gallen, 9000, Switzerland
Hôpital Fribourgeois-Freiburger Spital
Villars-sur-Glâne, 1752, Switzerland
Ankara Etlik City Hospital
Ankara, Keçiören, Turkey (Türkiye)
Marmara University Medical Faculty Hospital
Istanbul, Turkey (Türkiye)
Kocaeli University Medical School - Internal Medicine - Nephrology
Kocaeli, Turkey (Türkiye)
Erciyes University Faculty of Medicine
Melikgazi, Turkey (Türkiye)
Queen Elizabeth Hospital Birmingham
Birmingham, B152GW, United Kingdom
Cambridge University - Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Royal Liverpool University Hospital
Liverpool, L78YE, United Kingdom
Imperial College Healthcare NHS Trust
London, W21NY, United Kingdom
Royal Preston Hospital
Preston, PR2 9HT, United Kingdom
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 5, 2023
First Posted
September 21, 2023
Study Start
September 7, 2023
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
November 20, 2025
Record last verified: 2025-11