Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
130
Countries
1
Sites
3
Immune Bowel Disease (including Crohn's disease and Ulcerative colitis).
To demonstrate that induction treatment with CT-P13 SC is non-inferior to CT-P13 IV in terms of pharmacokinetics at Week 6.
Key facts
- Sponsor
- Centre Medico Chirurgical Ambroise Pare Hartmann
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 10 Jul 2024 → 14 May 2025
- Decision date (initial)
- 2024-05-21
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Celltrion Healthcare France SAS
External identifiers
- EU CT number
- 2023-508584-72-00
- ClinicalTrials.gov
- NCT06274294
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Pharmacokinetic
To demonstrate that induction treatment with CT-P13 SC is non-inferior to CT-P13 IV in terms of pharmacokinetics at Week 6.
Secondary objectives 10
- To demonstrate that induction treatment with CT-P13 SC is non-inferior to CT-P13 IV in terms of pharmacokinetics at Week 24.
- To compare the bioavailability of CT-P13 in both arms at Week 24.
- To compare induction treatment with CT-P13 SC and CT-P13 IV in terms of clinical response at Week 6.
- To evaluate disability in IBD patients treated with SC CT-P13 induction treatment at Week 6.
- To evaluate biomarker responses (fecal calprotectin) of SC CT-P13 induction treatment at Week 24.
- To compare induction treatment with CT-P13 SC and CT-P13 IV in terms of clinical remission at Week 24.
- To assess immunogenicity of SC CT-P13 induction treatment at Week 6 and Week 24.
- To evaluate biomarker responses (C-reactive protein) of SC CT-P13 induction treatment at Week 6.
- To evaluate safety of SC CT-P13 induction treatment.
- To describe patient satisfaction with treatment at Week 6 and Week 24.
Conditions and MedDRA coding
Immune Bowel Disease (including Crohn's disease and Ulcerative colitis).
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10009900 | Colitis ulcerative | 100000004856 |
| 20.0 | PT | 10011401 | Crohn's disease | 100000004856 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Passport cohort This is a multicenter, randomized, open label, controlled trial, comparing two schemes of infliximab
CT-P13 induction: initiation of SC treatment vs IV standard induction of CT-P13.
|
Randomised Controlled | None | Experimental arm SC CTP13 induction: Self-injection education by a nurse o SC induction of 240 mg of CT-P13 o Supply of SC injections (120 mg) to be administered subcutaneously at Week 1, Week 2, Week 3, Week 4 o Prescription for SC CT-P13 treatment (120 mg SC once every 2 weeks) to be retrieved from local pharmacy as part of routine practice for Week 6 Control arm IV CTP13 induction: IV induction of 5 mg/kg of CT-P13 (two-hour infusion) - Treatment provided by Celltrion Healthcare France SAS. o Appointment scheduling for the infusions at W2 (5 mg/kg of CT-P13 - treatment provided by the Celltrion Healthcare France SAS) and prescription for SC CT-P13 treatment (120 mg once every 2 weeks) from week 6 to be retrieved from local pharmacy as part of routine practice |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Male or female, aged at least 18 years old.
- Diagnosis of inflammatory bowel disease according to the ECCO criteria for at least 3 months: ● CD (Crohn’s disease) ● UC (Ulcerative colitis)
- Patients had received conventional therapy for active UC (corticosteroids alone or in combination with thiopurines and 5-aminosalicylates) or CD (corticosteroids and/or immunomodulators) but had not responded despite an adequate course of therapy.
- Patient has active CD or UC with at least one objective sign of disease activity on biology, endoscopy or imaging.
- Initiation of infliximab CT-P13 as part of standard of care.
- Patient suffering from anal suppuration related to CD can be included.
- Person who has received full information about the organization of the research, who has not objected to his or her participation and to the use of his or her data.
- Person affiliated to or beneficiary of a social security plan.
Exclusion criteria 7
- Combination therapy with an immunomodulator except for patients suffering from anal suppuration related to CD.
- Patient who has allergies to any of the excipients of infliximab CT-P13 or any other murine and/or human proteins or patient with a hypersensitivity to immunoglobulin product.
- Patient who had current or past history of chronic infection with hepatitis C or human immunodeficiency virus (HIV)-1 or -2 or current infection with hepatitis B.
- Patient who had acute infection requiring oral antibiotics within 2 weeks or parenteral injection of antibiotics within 4 weeks prior to the first administration of the study drug, other serious infection within 6 months prior to the first administration of study drug or recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug.
- Patients with a positive interferon-γ release assay (IGRA) or latent tuberculosis (TB) prior to initiation of biologic therapy.
- Person referred in articles L.1121-5, L. 1121-7 and L.1121-8 of the Public Health Code: pregnant woman, parturient, or breastfeeding woman, minor person (non-emancipated), adult person under legal protection (any form of public guardianship), adult person incapable of giving consent.
- Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Ctrough measurement (residual concentration of CT-P13) at Week 6.
Secondary endpoints 10
- Ctrough measurement at Week 24.
- AUC assessed at Week 24.
- Clinical response at Week 6: • Defined for UC as a decrease in the partial Mayo score from baseline of 30% or more and 3 or more points, along with either a rectal bleeding subscore of 0 or 1 or a decrease in the rectal bleeding subscore of 1 point or more; • Defined for CD as a decrease from baseline in CDAI score of at least 100 points or a total CDAI score < 150.
- IBD disability index collected at Week 6.
- Fecal calprotectin at Week 24 (the samples are collected at Weeks 0, 6 and 24).
- Clinical remission at Week 24: • Defined for UC as a total Mayo score of ≤ 2 with no individual subscore >1, and a rectal bleeding subscore of 0 at week 24 in active UC patients evaluated in semi-blind (assessment will be done by another investigator without information on the treatment); • Defined for CD as a CDAI score < 150 evaluated in semi-blind (assessment will be done by another investigator without information on the treatment).
- Presence of antibodies to infliximab at Week 6 and Week 24.
- Concentration of CRP up to week 6 (the samples are collected at weeks 0, 6 and 24).
- Adverse events, including injection site reactions and hypersensitivity reactions (from Baseline up to 6 weeks and 24 weeks).
- Treatment Satisfaction Questionnaire for Medication (TSQM) collected at Week 6 and Week 24.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Remsima 120 mg solution for injection in pre-filled syringe
PRD7753572 · Product
- Active substance
- Infliximab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 240 mg milligram(s)
- Max total dose
- 240 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB02 — -
- Marketing authorisation
- EU/1/13/853/006
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Induction treatment with subcutaneous Remsima instead of intraveineus infusion of Remsima.
Comparator 2
Remsima 100 mg powder for concentrate for solution for infusion
PRD2620248 · Product
- Active substance
- Infliximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB02 — -
- Marketing authorisation
- EU/1/13/853/002
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Remsima 100 mg powder for concentrate for solution for infusion
PRD2620218 · Product
- Active substance
- Infliximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB02 — -
- Marketing authorisation
- EU/1/13/853/001
- MA holder
- CELLTRION HEALTHCARE HUNGARY KFT
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Medico Chirurgical Ambroise Pare Hartmann
- Sponsor organisation
- Centre Medico Chirurgical Ambroise Pare Hartmann
- Address
- 25 Boulevard Victor Hugo
- City
- Neuilly-Sur-Seine
- Postcode
- 92200
- Country
- France
Scientific contact point
- Organisation
- Centre Medico Chirurgical Ambroise Pare Hartmann
- Contact name
- Clinical Project Manager
Public contact point
- Organisation
- Centre Medico Chirurgical Ambroise Pare Hartmann
- Contact name
- Clinical Project Manager
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ended | 130 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Medico Chirurgical Ambroise Pare Hartmann
Gastroenterology, 25 Boulevard Victor Hugo, 92200, Neuilly-Sur-Seine
Centre Hospitalier Universitaire De Saint Etienne
Gastroenterology, Avenue Albert Raimond, 42270, Saint Priest En Jarez
CHRU De Nancy
Gastroenterology, 29 Avenue Du Mal De Lattre De Tassigny, 54000, Nancy
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 |
|---|---|---|---|---|---|
| France | 2024-07-10 | 2024-07-10 | 2024-09-19 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-48489
- Halt date
- 2024-09-19
- Planned restart
- 2024-09-27
- Member states concerned
- France
- Publication date
- 2024-09-26
- Reason
- Sponsor decision
- Explanation
- Following the SB-48482 serious breach declared on September 26, 2024, the sponsor has taken the decision to temporarily suspend inclusions for centers 01, 02 and 03.
The sponsor, CMC Ambroise Paré Hartmann, has mandated the CRO Paris IBD Center (PIBDC) for the management of the PASSPORT study, including regulatory aspects (written agreement). On September 18, 2024, the sponsor identified that the following centers were not approved by the ethic committee:
• 250-04 (CHU Amiens - Picardie) : SIV on 30/08/2024, Activation on 11/09/2024 and FPFV on 11/09/2024
To date, 2 patients screened, one of whom randomized and treated.
• 250-05 (Hôpital Henri-Mondor) : no SIV
• 250-06 (Hospices Civils de Lyon - HCL) : no SIV
The sponsor immediately notified the PIBDC team via written email and phone call. On September 19, 2024, the PIBDC confirmed the occurrence of this operational breach. The breach constitutes a violation of regulatory procedures and indirectly affects patient safety. the sponsor put the decision to on-hold inclusion to perform root cause analysis. PIBDC notified this decision to authorized centers (Institut des MICI - CMC Ambroise Paré Hartmann, CHRU Nancy and CHU Saint-Etienne).
The inclusions at centers 01, 02, and 03 will remain suspended until regulatory compliance is verified by the PIBDC and sponsor. - Follow-up measures
- Actions already taken:
1.CHU Amiens-Picardie Notification:
On September 19, after learning that center 250-04 had not received the necessary approvals and that patient inclusions had occurred, the coordinating investigator at the sponsor's request contacted the Principal Investigator of the center to inform the center’s PI, to put the inclusions on hold-on and assess the patient safety concerning the randomized patient.
Given the patient's stable condition and the administration of the first subcutaneous dose as per the experimental arm, it was decided to maintain the current treatment without modifications, after expert consultation (cf infra). The patient with her approval will continue in the experimental schema to ensure close monitoring of her safety. The center will request the patient to return for each injection to ensure proper monitoring and that everything proceeds smoothly.
2. Mondor Hospital and HCL Notification:
On September 19, PIBDC canceled the SIV at Mondor Hospital and HCL.
3. On-hold inclusion:
At the same time, the sponsor put the decision to on-hold inclusion to perform root cause analysis. PIBDC notified this decision to authorized centers (Institut des MICI - CMC Ambroise Paré Hartmann, CHRU Nancy and CHU Saint-Etienne).
4. Meeting between the sponsor, the PIBDC and the coordinating investigator:
On September 24, 2024, a meeting was held between the sponsor, the PIBDC team, and the coordinating investigator. The coordinating investigator shared details of their discussion with the PI from CHU Amiens-Picardie regarding the safety and the follow-up of the treated patient and their decision as experts in gastroenterology. The patient has been under the care of an expert gastroenterologist experienced in therapeutic trials. The patient meets the inclusion criteria and requires treatment with infliximab due to her disease.
To mitigate the situation, we will prioritize the patient’s safety by ensuring close monitoring. The patient will return for clinical follow-up for each injection in the experimental arm.
The issue arose due to lapses in the regulatory submission and approval process, which are currently being addressed to prevent recurrence.
The decision was made to continue the administration of the study drug as described in the experimental arm. The batch of study IMP is subject to strict controls, confirming the decision to continue treatment through Week 4. Transitioning to intravenous administration was ruled out due to a lack of knowledge. The coordinating investigator assured that continuing with the subcutaneous route poses no additional risk to the patient, and there is no loss of therapeutic opportunity.
Upcoming actions:
1. Maintenance of suspension of inclusions:
Inclusions at centers 01, 02, and 03 will remain suspended until regulatory compliance is verified by the PIBDC and sponsor.
Inclusions at centers 04, 05, and 06 will be suspended pending validation by the sponsor, and approval of a substantial amendment.
2. Substantial modification:
A substantial modification will be conducted by PIBDC at the request of the sponsor as soon as possible to add the 3 centers (CHU Amiens-Picardie, Hôpital Mondor and HCL) and to notify the temporary suspension of inclusions.
The document related to the substantial modification will be subjected to sponsor review before approbation.
3. Audit:
The sponsor will conduct an audit of the PIBDC to ensure full regulatory compliance for the study.
4. Patient safety:
Ensuring close monitoring and no risk to the patient.
5. Escalation plan in PIBDC CRO:
Corrective actions: Addressing the organizational and procedural gaps that contributed to the issue.
Preventive actions: Establish an escalation plan, communication plan, and implement a training plan for the project manager.
6. Documentation in the TMF:
Documentation in the TMF by PIBDC of CAPAs pending the audit. - Benefit-risk balance changed
- No
- Treatment stopped
- No
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 |
|---|---|---|---|
| PASSPORT_Summary of the Final Report SUM-134019
|
2026-05-13T19:07:46 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| PASSPORT_Summary of the Final Report | 2026-05-13T19:09:26 | Submitted | Laypersons Summary of Results |
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | PASSPORT_Summary of the Final Report_V2YB | 1 |
| Protocol (for publication) | D1_Protocol 2023-508584-72-00 | 1 |
| Recruitment arrangements (for publication) | Additionnal document | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 2 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF description | 1 |
| Subject information and informed consent form (for publication) | Patient notebook_Control arm | 3 |
| Subject information and informed consent form (for publication) | Patient notebook_Experimental arm | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC REMSIMA | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC REMSIMA EN | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_ SmPC REMSIMA FR | 1 |
| Summary of results (for publication) | PASSPORT_Summary of the Final Report_V2YB | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_EN EU CT number 2023-508584-72-00 | 1 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis_FR EU CT number 2023-508584-72-00 | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-05 | France | Acceptable 2024-05-17
|
2024-05-21 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-07-30 | France | Acceptable 2024-05-17
|
2024-07-30 |