Clinical trial • Phase III • Immunology|Rare Disease

INEBILIZUMAB for Immunoglobulin G4-related disease

Phase III trial of INEBILIZUMAB for Immunoglobulin G4-related disease.

Overview

Trial Therapeutic Area
Immunology|Rare Disease
Trial Disease
Immunoglobulin G4-related disease
Trial Stage
Phase III
Drug Modality
Monoclonal antibody

Key dates

Initial CTIS Submission Date
26-02-2024
First CTIS Authorization Date
27-03-2024

Trial design

Randomised, placebo: 10 ml (nominal) solution containing 20 mm histidine/histidine hydrochloride, 70 mm sodium chloride, 106 mm (4% [w/v]) trehalose dihydrate, and 0.01% (w/v) polysorbate 80 (placebo product described; dose/schedule not specified).-controlled Phase III trial in Netherlands, Germany, France and others.

Randomised
Yes
Comparator
Placebo: 10 mL (nominal) solution containing 20 mM histidine/histidine hydrochloride, 70 mM sodium chloride, 106 mM (4% [w/v]) trehalose dihydrate, and 0.01% (w/v) polysorbate 80 (placebo product described; dose/schedule not specified).
Target Sample Size
110
Trial Duration For Participant
364

Eligibility

Recruits 110 Vulnerable population selected. Informed consent must be provided by adult participants who have reached the age of consent in the applicable region (e.g., ≥18 years)..

Pregnancy Exclusion
6. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide (where spermicide is available) from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highlyeffective method of contraception.
Vulnerable Population
Vulnerable population selected. Informed consent must be provided by adult participants who have reached the age of consent in the applicable region (e.g., ≥18 years).

Inclusion criteria

  • {"criterion_text":"- 1.Male or female adults who have reached the age of consent in the applicable region (eg, ≥18 years in the US)\n- 2. Clinical diagnosis of IgG4-RD.\n- 3. Fulfillment of the 2019 ACR/EULAR classification criteria.\n- 4. Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or continuation of glucocorticoid (GC) treatment at the time of informed consent.\n- 5. IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD. One organ must meet the requirements for the ACR/EULAR classification criteria; the second organ is as defined by the investigator\n- 6. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide (where spermicide is available) from Day 1 through to the end of the study and must agree to continue using such precautions for at least 6 months after the final dose of IP. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highlyeffective method of contraception."}

Exclusion criteria

  • {"criterion_text":"- 1. History of solid organ or cell-based transplantation or known immunodeficiency disorder .\n- 2. Active malignancy or history of malignancy that was active within the last 10 years (some specific situations for cervical, skin, prostate or thyroid cancer are acceptable).\n- 3. Receipt of any biologic B cell-depleting therapy or non-depleting Bcell- directed therapy in prior 6 months.\n- 4. Receipt of non-biologic DMARD or immunosuppressive agent other than GCs within prior 4 weeks\n- 5. Active tuberculosis or high risk for tuberculosis; hepatitis C infection in absence of curative treatment; evidence of hepatitis B infection\n- 6. Live vaccine or therapeutic agent in prior 2 weeks\n- 7. Glomerular filtration rate < 30 mL/min/1.73 m2"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Time to disease flare, defined as the time in days from Day 1 (dosing) to the date of the first treated and AC-determined IgG4 RD flare within the 52-week RCP. The date of disease flare is defined as the date of initiation of any flare treatment (new or increased GC treatment, other immunotherapy, or interventional procedure) deemed necessary by the Investigator for the flare.","definition_or_measurement_approach":"Defined as time in days from Day 1 (dosing) to date of first treated and AC-determined IgG4-RD flare within the 52-week RCP. Date of flare = date of initiation of any flare treatment (new or increased GC treatment, other immunotherapy, or interventional procedure) deemed necessary by the Investigator."}

Secondary endpoints

  • {"endpoint_text":"- 1. Annualized flare rate for treated and AC-determined flares during the RCP.","definition_or_measurement_approach":"Annualized rate of treated and AC-determined flares during the RCP."}
  • {"endpoint_text":"- 2. The proportion of subjects achieving flare-free, treatment-free complete remission at Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined flare during the RCP, and no treatment for flare or disease control except the required 8-week GC taper.","definition_or_measurement_approach":"Proportion of subjects with no evident disease activity at Week 52, no AC-determined flare during RCP, and no treatment for flare/disease control except the required 8-week GC taper."}
  • {"endpoint_text":"- 3. The proportion of subjects achieving flare-free, corticosteroid-free complete remission at Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined flare during the RCP, and no corticosteroid treatment for flare or disease control except the required 8-week GC taper.","definition_or_measurement_approach":"Proportion of subjects with no evident disease activity at Week 52, no AC-determined flare during RCP, and no corticosteroid treatment for flare/disease control except required 8-week GC taper."}
  • {"endpoint_text":"- 4. Time to initiation of first treatment (medication or procedure) for new or worsening disease activity by the Investigator within the RCP, regardless of AC determination of flare.","definition_or_measurement_approach":"Time in days from baseline to initiation of first treatment for new or worsening disease activity by the Investigator within the RCP (regardless of AC determination)."}
  • {"endpoint_text":"- 5. Annualized flare rate for AC-determined flares, whether or not treated, during the RCP.","definition_or_measurement_approach":"Annualized rate of AC-determined flares (treated or untreated) during the RCP."}
  • {"endpoint_text":"- 6. Glucocorticoid use, calculated as the cumulative GC dose taken for the purpose of IgG4 RD disease control during the RCP.","definition_or_measurement_approach":"Cumulative glucocorticoid dose taken for disease control during the RCP."}
  • {"endpoint_text":"- 7. Incidence of treatment emergent adverse events (TEAEs), serious TESAEs, and TEAEs of special interest (AESIs) during the 52-week RCP and during the OLP.","definition_or_measurement_approach":"Incidence rates of TEAEs, serious TESAEs, and TEAEs of special interest during the 52-week RCP and OLP."}
  • {"endpoint_text":"- 8. The incidence of ADAs directed against inebilizumab during the RCP.","definition_or_measurement_approach":"Incidence of anti-drug antibodies (ADAs) against inebilizumab during the RCP."}

Recruitment

Planned Sample Size
110
Recruitment Window Months
99
Consent Approach
Informed consent obtained from adult participants who have reached the age of consent in the applicable region (eg, ≥18 years). Subject information and informed consent forms available in multiple languages (documents available in English, French, Dutch, Spanish, Italian, Polish, German).

Geography

Total Number Of Sites
15
Total Number Of Participants
90

Netherlands

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
25-03-2025
Processing Time Days
434
Number Of Sites
1
Number Of Participants
12

Sites

Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Clinical Immunology
Principal Investigator Name
Jan van Laar
Principal Investigator Email
j.vanlaar@erasmusmc.nl
Contact Person Name
Jan van Laar
Contact Person Email
j.vanlaar@erasmusmc.nl

Germany

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
14-04-2025
Processing Time Days
454
Number Of Sites
1
Number Of Participants
12

Sites

Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität München
Principal Investigator Name
Julia Mayerle
Principal Investigator Email
Julia.Mayerle@med.uni-muenchen.de
Contact Person Name
Julia Mayerle

France

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
26-02-2026
Processing Time Days
772
Number Of Sites
4
Number Of Participants
13

Sites

Site Name
Hopital Beaujon
Department Name
Service de Pancréatologie
Principal Investigator Name
Vinciane Rebours
Principal Investigator Email
vinciane.rebours@aphp.fr
Contact Person Name
Vinciane Rebours
Contact Person Email
vinciane.rebours@aphp.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Service de Médecine Interne
Principal Investigator Name
Alexandra Espitia
Principal Investigator Email
alexandra.espitiathibault@chu-nantes.fr
Contact Person Name
Alexandra Espitia
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service de Médecine Interne
Principal Investigator Name
Nicolas Schleinitz
Principal Investigator Email
nicolas.schleinitz@ap-hm.fr
Contact Person Name
Nicolas Schleinitz
Contact Person Email
nicolas.schleinitz@ap-hm.fr
Site Name
Hopital Huriez
Department Name
Service de Médecine Interne
Principal Investigator Name
Eric Hachulla
Principal Investigator Email
eric.hachulla@chru-lille.fr
Contact Person Name
Eric Hachulla
Contact Person Email
eric.hachulla@chru-lille.fr

Italy

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
13-02-2026
Processing Time Days
759
Number Of Sites
4
Number Of Participants
11

Sites

Site Name
Careggi University Hospital
Department Name
Department of Clinical and Experimental Medicine
Principal Investigator Name
Elena Silvestri
Principal Investigator Email
elena.silvestri@unifi.it
Contact Person Name
Elena Silvestri
Contact Person Email
elena.silvestri@unifi.it
Site Name
Ospedale San Giovanni Bosco
Department Name
SCdU Nephrology and Dyalisis - CMID
Principal Investigator Name
Savino Sciascia
Principal Investigator Email
savino.sciascia@unito.it
Contact Person Name
Savino Sciascia
Contact Person Email
savino.sciascia@unito.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR)
Principal Investigator Name
Lorenzo Dagna
Principal Investigator Email
dagna.lorenzo@unisr.it
Contact Person Name
Lorenzo Dagna
Contact Person Email
dagna.lorenzo@unisr.it
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
c/o Policlinico GB Rossi
Principal Investigator Name
Luca Frulloni
Principal Investigator Email
luca.frulloni@univr.it
Contact Person Name
Luca Frulloni
Contact Person Email
luca.frulloni@univr.it

Spain

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
04-03-2026
Processing Time Days
778
Number Of Sites
3
Number Of Participants
30

Sites

Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Internal Medicine
Principal Investigator Name
Irene Calatayud Marin
Principal Investigator Email
calatayud_ire@gva.es
Contact Person Name
Irene Calatayud Marin
Contact Person Email
calatayud_ire@gva.es
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Internal Medicine
Principal Investigator Name
Andres Gonzalez Garcia
Principal Investigator Email
andres.gonzalez@salud.madrid.org
Contact Person Name
Andres Gonzalez Garcia
Site Name
Hospital Universitari Vall D Hebron
Department Name
Internal Medicine
Principal Investigator Name
Fernando Martinez Valle
Principal Investigator Email
ferranmartinezvalle@gmail.com
Contact Person Name
Fernando Martinez Valle
Contact Person Email
ferranmartinezvalle@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
16-01-2024
Latest Decision Or Authorization Date
16-02-2026
Processing Time Days
762
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Narodowy Instytut Geriatrii Reumatologii I Rehabilitacji Im Prof. Dr Hab. Med. Eleonory Reicher
Department Name
Klinika Wczesnego Zapalenia Stawów
Principal Investigator Name
Maria Maślińska
Principal Investigator Email
maria.maslinska@spartanska.pl
Contact Person Name
Maria Maślińska
Contact Person Email
maria.maslinska@spartanska.pl
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Reumatologii i Chorób Wewnętrznych
Principal Investigator Name
Piotr Wiland
Principal Investigator Email
pwiland1@gmail.com
Contact Person Name
Piotr Wiland
Contact Person Email
pwiland1@gmail.com

Sponsor

Primary sponsor

Full Name
Horizon Therapeutics Ireland Designated Activity Company
Organisation Type
Pharmaceutical company
Country Of Registered Address
Ireland

Contract research organisations

Name
Medpace Inc.
Responsibilities
sponsorDuties codes: 1,12,15 (ePRO),2,3,6,7,9
Name
Parexel International Corp.
Responsibilities
sponsorDuties: 8
Name
Icon Public Limited Company
Responsibilities
sponsorDuties: 15 (Safety vendor and Firecrest Training Portal)

Third parties

  • {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"sponsorDuties codes: 1,12,15 (ePRO),2,3,6,7,9","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties: 15 (QP release)","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties: 15 (QP release)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"sponsorDuties: 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties: 15 (QP release)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties: 15 (TMF),7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties: 15 (QP release)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"sponsorDuties: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Public Limited Company","duties_or_roles":"sponsorDuties: 15 (Safety vendor and Firecrest Training Portal)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
INEBILIZUMAB
Active Substance
INEBILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS USE
Route
INTRAVENOUS USE
Maximum Dose
300 mg (max daily); 3000 mg (max total)
Investigational Product Name
10 mL (nominal) solution containing 20 mM histidine/histidine hydrochloride, 70 mM sodium chloride, 106 mM (4% [w/v]) trehalose dihydrate, and 0.01% (w/v) polysorbate 80
Modality
Other
Combination Treatment
Yes

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