Pharmacokinetics, Efficacy and Safety of CT-P13 Subcutaneous as Induction Therapy in Patients With Active CD or UC

Inflammatory Bowel Diseases Clinical Trial

— PASSPORT  

Official title:

The "PASSPORT Trial": Pharmacokinetics, Efficacy and Safety of CT-P13 Subcutaneous as Induction Therapy in Patients With Active Crohn's Disease or Ulcerative Colitis.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06274294
• Other study ID #: 2023/12
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 2024
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: CMC Ambroise Paré
• Contact: Angèle Benoit, M.Pharm.
• Phone: 0787518342
• Email: angele.benoit[@]institutdesmici.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare induction treatment with CT-P13 SC to induction treatment with CT-P13 IV in terms of pharmacokinetics in adult patients with inflammatory bowel disease (IBD) who have been diagnosed for at least 3 months and for whom the physician has decided to initiate treatment with infliximab CT-P13 as part of the standard of care. The main aim of this study is to demonstrate that induction treatment with CT-P13 SC is non-inferior to CT-P13 IV in terms of pharmacokinetics at Week 6.

Description:

The subcutaneaous formulation of infliximab CT-P13 represents a promising approach in the treatment of inflammatory bowel disease (IBD), with an efficacy/safety/immunogenicity profile similar or even improved compared to the intravenous formulation of CT-P13. For patients, SC administration can offer benefits over their daily activities by reducing the frequency of days spent in the hospital to receive infusions. The SC administration may offer convenience for the healthcare system, optimizing the organizational impact due to the preparation and administration of the IV infusion, allowing resources to be used more efficiently, and reducing direct costs associated with the infusion. There are no clinical trials with Remsima® 120 mg given subcutaneously without IV loading doses of CT-P13 in patients with IBD. However, population pharmacokinetic and pharmacokinetic/pharmacodynamic modelling and simulation predicted comparable CT-P13 exposure (AUC over 8 weeks) and efficacy from Week 6 onward in rheumatoid arthritis patients treated with Remsima® 120 mg given without IV loading doses of CT-P13 when compared with Remsima® 3 mg/kg given intravenously at weeks 0, 2 and 6, and then every 8 weeks. For the dosing regimen with subcutaneous loading in patients with rheumatoid arthritis, the predicted median AUC value was 17,400 μg·h/mL from Week 0 to 6 which was approximately 1.8 fold lower than the predicted median AUC value for the dosing regimen with CT-P13 IV loading doses (32,100 μg·h/mL). Whereas the predicted median AUC values from Week 6 to 14 were comparable between the two dosing regimens with SC loading and IV loading (19,600 and 18,100 μg·h/mL, respectively).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 130
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, aged at least 18 years old.

2. Diagnosis of inflammatory bowel disease according to the ECCO criteria for at least 3

months:

• CD (Crohn's disease)
• UC (Ulcerative colitis)

3. 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.

4. Patient has active CD or UC with at least one objective sign of disease activity on biology, endoscopy or imaging.

5. Initiation of infliximab CT-P13 as part of standard of care.

6. Patient suffering from anal suppuration related to CD can be included.

7. 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.

8. Person affiliated to or beneficiary of a social security plan.

Exclusion Criteria:

1. Combination therapy with an immunomodulator except for patients suffering from anal suppuration related to CD.

2. 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.

3. 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.

4. 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.

5. Patients with a positive interferon-? release assay (IGRA) or latent tuberculosis (TB) prior to initiation of biologic therapy.

6. 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.

7. Person deprived of liberty for judicial or administrative decision, person under psychiatric care as referred in articles L. 3212-1 and L. 3213-1.

Related Conditions & MeSH terms

• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Drug:
• CT-P13
Induction treatment.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
CMC Ambroise Paré	Celltrion HealthCare France, Paris IBD Center

References & Publications (2)

Iannone F, Conti F, Cauli A, Farina A, Caporali R. Subcutaneously-Administered Infliximab in the Management of Rheumatoid Arthritis: A Short Narrative Review of Current Clinical Evidence. J Inflamm Res. 2022 Jun 1;15:3259-3267. doi: 10.2147/JIR.S240593. e — View Citation

Schreiber S, Ben-Horin S, Leszczyszyn J, Dudkowiak R, Lahat A, Gawdis-Wojnarska B, Pukitis A, Horynski M, Farkas K, Kierkus J, Kowalski M, Lee SJ, Kim SH, Suh JH, Kim MR, Lee SG, Ye BD, Reinisch W. Randomized Controlled Trial: Subcutaneous vs Intravenous — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ratio SC/IV	The ratio (SC/IV) of log-normal means of Ctrough at W6 and its 95% CI. Non inferiority will be considered as demonstrated if the lower limit of the 95%CI is higher than 80%.	Week 6
Secondary	Ctrough at week 24 (non-inferiority)		Week 24
Secondary	AUC at week 24		Week 24
Secondary	Clinical response at week 6 and week 24	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.	Weeks 6 and 24
Secondary	IBD disability index at week 6		Week 6
Secondary	Fecal calprotectin at week 24		Week 24
Secondary	Clinical remission at week 6 and week 24	Defined for UC as a partial Mayo score of = 2 with no individual subscore >1, and a rectal bleeding subscore of 0 at week 6 in active UC patients evaluated in semi-blind (assessment will be done by another investigator without information on the treatment); 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).	Weeks 6 and 24
Secondary	Presence of antibodies to infliximab at Week 6 and Week 24		Weeks 6 and 24
Secondary	Concentration of C-reactive protein up to week 6 (the samples are collected at weeks 0, 6 and 24)		Up to Week 6
Secondary	Adverse events, including injection site reactions and hypersensitivity reactions	Number of participants, number of AEs per patient, number of injection site reactions and hypersensitivity reactions per patient.	From Baseline up to 6 weeks and 24 weeks
Secondary	TSQM collected at Week 6 and Week 24	The Treatment Satisfaction Questionnaire for Medication consists of 14 items that results in four specific domains: Effectiveness, Side Effects, Convenience, and one global scale item, Global Satisfaction. Scores for each domain are computed by adding the TSQM items in each domain and then transforming the composite score into a value ranging from 0 to 100.	24 months