Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
247
Countries
7
Sites
37
Autoimmune disease
To evaluate the efficacy and safety of zetomipzomib in patients with active Class III or IV (with or without Class V; Class III/IV +/-V) LN and for those with pure Class V LN
Key facts
- Sponsor
- Kezar Life Sciences Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 25 Oct 2023 → 8 Nov 2024
- Decision date (initial)
- 2023-10-02
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Kezar Life Sciences, Inc.
External identifiers
- EU CT number
- 2022-502227-22-00
- ClinicalTrials.gov
- NCT05781750
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate the efficacy and safety of zetomipzomib in patients with active Class III or IV (with or without Class V; Class III/IV +/-V) LN and for those with pure Class V LN
Secondary objectives 1
- To evaluate zetomipzomib compared with placebo in patients with active Class III/IV +/-V LN on background MMF or equivalent, and corticosteroids based upon current guideline-driven standard of care
Conditions and MedDRA coding
Autoimmune disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10029142 | Nephritis systemic lupus erythematosus | 10038359 |
| 21.1 | PT | 10025140 | Lupus nephritis | 100000004857 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | tbc tbc
|
Randomised Controlled | Double | [{"id":50652,"code":1,"name":"Subject"},{"id":50651,"code":3,"name":"Monitor"},{"id":50653,"code":2,"name":"Investigator"}] | Experimental: zetomipzomib 30 mg + standard-of-care: Initial 30 mg dose of zetomipzomib, followed by weekly doses of 30 mg zetomipzomib through 52 weeks of the treatment period. Experimental: zetomipzomib 60 mg + standard-of-care: Initial 30 mg dose of zetomipzomib, followed by weekly doses of 60 mg zetomipzomib through 52 weeks of the treatment period. Placebo Comparator: placebo + standard-of-care: Initial 30 mg dose of placebo, followed by weekly doses (30 mg or 60 mg) of placebo through 52 weeks of the treatment period. |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-004382-39 | An Open-label Extension to the Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients with Active Polymyositis or Dermatomyositis . |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Body mass index of ≥18 kg/m^2 eGFR ≥30 mL/min/1.73 m^2 Unequivocally positive ANA test result and/or a positive anti-dsDNA serum antibody test Diagnosis of LN according to 2003 or 2018 ISN/RPS criteria and confirmed by renal biopsy performed within 12 months prior to Screening. UPCR ≥1.0 (Class III/IV +/-V) or UPCR ≥2.0 (Class V) Adequate hematologic, hepatic, and renal function
Exclusion criteria 1
- 1.Current or medical history of: - Central nervous system manifestations of SLE - Overlapping autoimmune condition that may affect study assessments/outcomes - Antiphospholipid syndrome with history of thromboembolic event of within the 52 weeks prior to Screening - Thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies (i.e., plasmapheresis or acute blood or platelet transfusions - Solid organ transplant or planned transplant during study - Malignancy of any type, with exceptions for non-melanoma skin cancers and certain cancers >5 years ago 2. Has received dialysis within the 52 weeks prior to Screening 3. Positive test at Screening for HIV, hepatitis B/C 4. Known intolerance to MMF or equivalent and corticosteroids
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary efficacy endpoint is the proportion of patients achieving CRR at Week 37.
Secondary endpoints 3
- The key secondary efficacy endpoints will evaluate the proportion of patients achieving the following: • PRR at Week 25, Week 37, and Week 53 • CRR at Week25 and Week 53 The other secondary efficacy endpoints include the following: • Percentage change from Baseline in UPCR by visit • Time to event (CRR, PRR, death or renal event)
- • Proportion of patients achieving CRR (at Weeks 25, 37, and 53) with successful taper of prednisone or equivalent by Week 17 • Proportion of patients achieving CRR (at Weeks 25, 37, and 53) with no use of prednisone or equivalent during the 8 weeks prior to the renal response assessment • Proportion of patients with UPCR ≤0.5 at Weeks 13, 25, 37, and 53
- • Proportion of patients achieving CRR with UPCR ≤ upper limit of normal (ULN) at Weeks 25, 37, and 53 • Change from Baseline in clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, excluding complement and anti-dsDNA components • Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 5
-
V07AB · Product
- Pharmaceutical form
- PHF00017MIG
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 0.92 ml millilitre(s)
- Max total dose
- 0.92 ml millilitre(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sterile Water For Injection, 0.92 mL (Prefilled Syringe)
PRD10367627 · Product
- Active substance
- Water for Injection
- Pharmaceutical form
- SOLVENT FOR PARENTERAL USE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 0.92 ml millilitre(s)
- Max total dose
- 0.92 ml millilitre(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- KEZAR LIFE SCIENCES, INC.
- Paediatric formulation
- No
- Orphan designation
- No
Myfenax 500 mg film-coated tablets
PRD8167789 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 3 g gram(s)
- Max total dose
- 1022 g gram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- EU/1/07/438/010
- MA holder
- TEVA B.V
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Myfenax 500 mg film-coated tablets
PRD3926751 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 3 g gram(s)
- Max total dose
- 1022 g gram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- EU/1/07/438/005
- MA holder
- TEVA B.V
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD10367626 · Product
- Active substance
- Zetomipzomib
- Substance synonyms
- 4,5-Anhydro-1-(1-cyclopenten-1-yl)-1,2-dideoxy-4-C-methyl-2-((N-(2-(4-morpholinyl)acetyl)-L-alanyl-(βR)-β-hydroxy-O-methyl-L-tyrosyl)amino)-D-erythro-3-pentulose, KZR-616, (2S,3R)-N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 3120 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- KEZAR LIFE SCIENCES, INC.
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- 18-6720 & 18-6635
Placebo 1
sterilized lyophilized powder with no active
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 3
-
H02AB · Product
- Pharmaceutical form
- PHF00231MIG
- Route of administration
- ORAL USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 3815 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- H02AB — GLUCOCORTICOIDS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08872MIG · Substance
- Active substance
- Methylprednisolone
- Pharmaceutical form
- POWDER FOR SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD3680541 · Product
- Active substance
- Methylprednisolone Sodium Succinate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 3 g gram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB04 — METHYLPREDNISOLONE
- Marketing authorisation
- 89739.00.00
- MA holder
- ACIS ARZNEIMITTEL GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Kezar Life Sciences Inc.
- Sponsor organisation
- Kezar Life Sciences Inc.
- Address
- 4000 Shoreline Court Suite 300
- City
- South San Francisco
- Postcode
- 94080-2005
- Country
- United States
Scientific contact point
- Organisation
- Kezar Life Sciences Inc.
- Contact name
- Clinical Operations
Public contact point
- Organisation
- Kezar Life Sciences Inc.
- Contact name
- Clinical Development
Third parties 15
| Organisation | City, country | Duties |
|---|---|---|
| PPD Global Ltd. ORG-100007531
|
Marousi, Greece | On site monitoring, Other |
| Primevigilance Limited ORG-100027742
|
Guildford, United Kingdom | Other, Code 8 |
| Fisher Clinical Services GmbH ORG-100017323
|
Rheinfelden (Baden), Germany | Other |
| Clinical Ink Inc. ORG-100042433
|
Horsham, United States | Other |
| Jumo Health USA Inc. ORG-100044054
|
New Haven, United States | Other |
| Scout Clinical ORG-100042228
|
Dallas, United States | Other |
| PPD Development Ireland Limited ORG-100007309
|
Athlone, Ireland | Other |
| PPD Development LP ORG-100011560
|
Wilmington, United States | On site monitoring, Code 12, Code 13, Code 14, Laboratory analysis, Code 5, Data management, E-data capture |
| Signant Health LLC ORG-100040732
|
Blue Bell, United States | Interactive response technologies (IRT) |
| Fisher Clinical Services GmbH ORG-100012942
|
Allschwil, Switzerland | Other |
| Crisalis LLC ORG-100047297
|
Oklahoma City, United States | Other |
| MARKEN Germany GmbH ORG-100017196
|
Kelsterbach, Germany | Other |
| Fisher Clinical Services UK Limited ORG-100012049
|
Horsham, United Kingdom | Other |
| PPD Global Central Labs ORG-100046496
|
Zaventem, Belgium | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other |
Locations
7 EU/EEA countries · 37 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Croatia | Ended | 6 | 3 |
| France | Ended | 8 | 4 |
| Germany | Ended | 6 | 2 |
| Greece | Ended | 10 | 5 |
| Italy | Ended | 22 | 8 |
| Portugal | Ended | 12 | 6 |
| Spain | Ended | 18 | 9 |
| Rest of world
South Africa, Serbia, Brazil, Canada, Singapore, Argentina, Israel, Taiwan, Australia, China, Turkey, Colombia, United States, United Kingdom, Korea, Republic of
|
— | 165 | — |
Investigational sites
KBC Split
Rheumatology, Clinical Immunology and Allergology, Soltanska 1, 21000, Split
University Hospital Centre Zagreb
Nephrology, Art. Hypertension, Dialysis and Transplantation, Ulica Mije Kispatica 12, Zagreb, Grad Zagreb
Poliklinika Solmed d.o.o.
n/a, Preradoviceva Ulica 20, Zagreb, Grad Zagreb
Assistance Publique Hopitaux De Paris
Département de Néphrologie et Transplantation, 51 Av Du Mal De Lattre De Tassigny, 94000, Creteil
Hospices Civils De Lyon
Département de Néphrologie, 5 Place D Arsonval, 69437, Lyon Cedex 03
Assistance Publique Hopitaux De Paris
Département de Médecine interne, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Centre Hospitalier Universitaire Amiens Picardie
Département de Néphrologie, 1 Rond Point Du Professeur Christian Cabrol, 80054, Amiens
Medical Center - University Of Freiburg
Klinik für Rheumatologie und Klinische Immunologie, Hugstetter Strasse 55, Stuehlinger, Freiburg Im Breisgau
Universitaetsklinikum Bonn AöR
Nephrologie, Venusberg-Campus 1, Venusberg, Bonn
Laiko General Hospital Of Athens
1st Department of Propaedeutic Internal, Agiou Thoma (goudi) 17, 115 27, Athens
General University Hospital Of Larissa
Rheumatology Clinic, P. O. Box 1425, 411 10, Larissa
Laiko General Hospital Of Athens
Clinic of Nephrology and Renal Transplanation, Agiou Thoma (goudi) 17, 115 27, Athens
Ippokratio General Hospital Of Thessaloniki
Department of Nephrology, Konstadinoupoleos 49, 546 42, Thessaloniki
Laiko General Hospital Of Athens
Clinic of Pathological Physiology of the GHA “Laiko”, Laboratory of Pathological Physiology, Agiou Thoma (goudi) 17, 115 27, Athens
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
UOSD di Immunologia Clinica, Largo Francesco Vito 1, 00168, Rome
Fondazione Policlinico Universitario Campus Bio-Medico
Immuno-rheumatology Unit, Via Alvaro Del Portillo N 200, 00128, Rome
Cattinara Hospital
SC Nefrologia e Dialisi di Trieste, Strada Di Fiume 447, 34149, Trieste
Istituti Clinici Scientifici Maugeri In Forma Abbreviata Istituti Clinici Scientifici Maugeri O Anche Ics Maugeri O Maugeri S.p.A. Sb
Unit of Nephrology and Dialysis, Via Salvatore Maugeri 4, 27100, Pavia
Ospedale San Raffaele S.r.l.
Unita' Di Immunobioterapia Del Melanoma E Dei Tumori, Via Olgettina 60, 20132, Milan
University Hospital Consorziale Policlinico
Nephrology, Dialysis and Transplant Unit, Piazzale Giulio Cesare 11, 70124, Bari
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department of Translational Medicine, Corso Giuseppe Mazzini 18, 28100, Novara
Humanitas Research Hospital
Biomedical Sciences – Nephrology Unit, Via Alessandro Manzoni 56, 20089, Rozzano
Centro Hospitalar Universitario De Lisboa Norte E.P.E.
Nephrology Department, Avenida Professor Egas Moniz, 1649-035, Lisbon
Centro Hospitalar de Setubal E.P.E.
Nephrology, Rua Camilo Castelo Branco, 2910-446, Setubal
CCAB Centro Clinico Academico Braga Associacao
Rheumatology Department, Lugar De Sete Fontes S Victor, 4710-243, Braga
Centro Hospitalar Universitario Do Porto E.P.E.
Internal Medicine, Largo Professor Abel Salazar, 4050-011, Porto
Centro Hospitalar De Lisboa Ocidental E.P.E.
Internal Medicine, Nephrology, Av Prof Dr Reinaldo Dos Santos, 2790-134, Carnaxide
Hospital Da Senhora Da Oliveira Guimaraes E.P.E.
Internal Medicine, Rua Dos Cuteleiros De Guimaraes, 4835-044, Guimaraes
University Hospital Virgen Del Rocio S.L.
Nephrology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Clinic De Barcelona
Nephrology, Calle Villarroel 170, 08036, Barcelona
Fundacio Puigvert
Nephrology, Calle De Cartagena 340-350, 08025, Barcelona
Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida
Nephrology, Av Alcalde Rovira Roure 80, 25198, Lleida
Hospital Clinico San Carlos
Nephrology, Calle Del Profesor Martin Lagos S/n, 28040, Madrid
Hospital Universitario De Navarra
Nephrology department, Irunlarrea Kalea 3, 31008, Pamplona
Hospital Universitario 12 De Octubre
Nephrology, Bloque D, Avenida De Cordoba S/n, Madrid
Bellvitge University Hospital
Nephrology, Carrer De La Feixa Llarga Sn, 08907, L'hospitalet De Llobregat
Hospital General Universitario Gregorio Maranon
Rheumatology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Croatia | 2023-11-16 | 2024-03-27 | 2024-09-24 | ||
| Greece | 2023-10-31 | 2024-01-18 | 2024-09-24 | ||
| Portugal | 2023-10-25 | ||||
| Spain | 2023-10-27 | 2024-04-23 | 2024-09-24 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 4 · Art. 38 CTR
Temporary halt TH-50684
- Halt date
- 2024-09-24
- Member states concerned
- Greece
- Publication date
- 2024-10-09
- Reason
- Safety related (clinical or pre-clinical results)
- Follow-up measures
- The Sponsor has notified all study investigators and is in the process of notifying all relevant global regulatory authorities. Investigators and study teams have been instructed to continue to follow patients and perform all safety and efficacy procedures per the schedule of assessments.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-50681
- Halt date
- 2024-09-24
- Member states concerned
- Portugal
- Publication date
- 2024-10-09
- Reason
- Safety related (clinical or pre-clinical results)
- Follow-up measures
- The Sponsor has notified all study investigators and is in the process of notifying all relevant global regulatory authorities. Investigators and study teams have been instructed to continue to follow patients and perform all safety and efficacy procedures per the schedule of assessments.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-50679
- Halt date
- 2024-09-24
- Member states concerned
- Spain
- Publication date
- 2024-10-09
- Reason
- Safety related (clinical or pre-clinical results)
- Follow-up measures
- The Sponsor has notified all study investigators and is in the process of notifying all relevant global regulatory authorities. Investigators and study teams have been instructed to continue to follow patients and perform all safety and efficacy procedures per the schedule of assessments.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-50686
- Halt date
- 2024-09-24
- Member states concerned
- Croatia
- Publication date
- 2024-10-09
- Reason
- Safety related (clinical or pre-clinical results)
- Follow-up measures
- The Sponsor has notified all study investigators and is in the process of notifying all relevant global regulatory authorities. Investigators and study teams have been instructed to continue to follow patients and perform all safety and efficacy procedures per the schedule of assessments.
- Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| Kezar_KZR-616-202_CSR Summary of results SUM-92755
|
2025-08-15T03:02:21 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Summary of the results of the clinical trial | 2025-08-15T03:03:38 | Submitted | Laypersons Summary of Results |
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | B1_Kezar_KZR-616-202_CSR Summary_Cover Letter | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_DE_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_EN_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_ES_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_FR_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_GR_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_HR_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_IT_Public | N/A |
| Laypersons summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Layperson Summary_2022-502227-22-00_PT_Public | N/A |
| Summary of results (for publication) | B1_Kezar_KZR-616-202_CSR Summary_Cover Letter | N/A |
| Summary of results (for publication) | D1_Kezar_KZR 616-202_CSR Summary_2022-502227-22-00_Public | N/A |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-09 | Spain | Acceptable with conditions 2023-09-15
|
2023-09-15 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-01-29 | Spain | Acceptable 2024-04-19
|
2024-04-19 |