Clinical trial • Phase I/II | Phase III • Endocrinology

ZIMISLECEL for Type 1 diabetes mellitus | Impaired hypoglycemic awareness | Severe hypoglycemia

Phase I/II | Phase III trial of ZIMISLECEL for Type 1 diabetes mellitus | Impaired hypoglycemic awareness | Severe hypoglycemia.

Overview

Trial Therapeutic Area
Endocrinology
Trial Disease
Type 1 diabetes mellitus | Impaired hypoglycemic awareness | Severe hypoglycemia
Trial Stage
Phase I/II | Phase III
Drug Modality
Cell therapy

Key dates

Initial CTIS Submission Date
05-09-2024
First CTIS Authorization Date
02-10-2024

Trial design

open-label, none/not specified-controlled Phase I/II | Phase III trial across 6 sites in France, Germany, Italy and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
36
Trial Duration For Participant
365

Eligibility

Recruits 36 Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information sheets and informed consent forms for adults are provided (L1_SIS and ICF Main Adult, Pre-Screening, Pregnancy ICF and country-specific ICFs). No information on assent or parental consent for minors is provided in the available CTIS data..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Subject information sheets and informed consent forms for adults are provided (L1_SIS and ICF Main Adult, Pre-Screening, Pregnancy ICF and country-specific ICFs). No information on assent or parental consent for minors is provided in the available CTIS data.

Inclusion criteria

  • {"criterion_text":"-Clinical history and laboratory evidence of T1D"}
  • {"criterion_text":"-At least 2 episodes of severe hypoglycemia (confirmed by independent adjudication for subjects in Parts B and C) in the 12 months prior to signing of informed consent at Screening."}
  • {"criterion_text":"-Reduced awareness of hypoglycemia at Screening"}
  • {"criterion_text":"-Consistent use of continuous glucose monitor (CGM) for at least 3 months before Screening. In regions where CGM is not standard of care for T1D, subjects are exempted from the requirement for use of CGM before Screening."}
  • {"criterion_text":"-Compatible blood group (A or AB)"}

Exclusion criteria

  • {"criterion_text":"-Prior islet cell transplant, organ transplant, or cell therapy"}
  • {"criterion_text":"-Advanced complications associated with diabetes including untreated proliferative retinopathy, skin ulcers, or amputations attributable to diabetes."}
  • {"criterion_text":"-Subjects who have any 1 of the following criteria: o Insulin requirements: >0.8 U/(kg*day), >55 U/day, or <10 U/day; o HbA1c: <6.0% or >9.5%"}
  • {"criterion_text":"-Clinically significant active infection or chronic infection such as hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and/or tuberculosis (TB); or invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within 1 year prior to signing of informed consent at Screening."}
  • {"criterion_text":"-Negative screen for Epstein-Barr virus (EBV) by immunoglobulin G (IgG) determination"}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Part A - Safety and tolerability based on treatment-emergent adverse events (TEAEs; including incidence and severity of adverse events [AEs] and serious adverse events [SAEs]), clinical laboratory values, vital signs, standard 12-lead ECGs, and imaging findings","definition_or_measurement_approach":"Safety and tolerability assessed by incidence and severity of TEAEs (including AEs and SAEs), clinical laboratory values, vital signs, standard 12-lead ECGs, and imaging findings."}
  • {"endpoint_text":"-Part B and C - The following endpoints apply to the analysis of all infused subjects who intended to receive 0.8 × 10E9 total SC-islet cells with 1 infusion: •Proportion of subjects who are insulin independent at Day 365 after VX-880 infusion","definition_or_measurement_approach":"Proportion of infused subjects who are insulin independent at Day 365 post-infusion (analysis population: all infused subjects who intended to receive 0.8 × 10^9 SC-islet cells in one infusion)."}

Secondary endpoints

  • {"endpoint_text":"-Part B and C: Secondary Endpoints - Proportion of subjects free of SHEs from Day 90 through Day 365 (inclusive) and HbA1c <7.0% at Day 365 after VX 880 infusion","definition_or_measurement_approach":"Proportion free of severe hypoglycemic events (SHEs) between Day 90 and Day 365 inclusive; and proportion with HbA1c <7.0% at Day 365 post-infusion."}
  • {"endpoint_text":"-Part B and C: Secondary Endpoints - Change from baseline in HbA1c at Day 365 after VX-880 infusion","definition_or_measurement_approach":"Change from baseline in HbA1c measured at Day 365 post-infusion compared to baseline."}
  • {"endpoint_text":"-Part B and C: Secondary Endpoints- Proportion of subjects who achieve insulin independence and are insulin independent 12 months later, with absence of SHEs","definition_or_measurement_approach":"Proportion of subjects who achieve insulin independence and remain insulin independent 12 months later without SHEs."}
  • {"endpoint_text":"-Part B and C: Secondary Endpoints- Proportion of subjects who maintain insulin independence for at least 1 year","definition_or_measurement_approach":"Proportion of subjects maintaining insulin independence for ≥1 year post-achievement."}
  • {"endpoint_text":"-Part B and C: afety and tolerability based on TEAEs (including incidence and severity of AEs and SAEs), clinical laboratory values, vital signs, standard 12-lead ECGs, and imaging findings","definition_or_measurement_approach":"Safety and tolerability endpoints measured by TEAE incidence and severity, clinical lab values, vital signs, 12-lead ECGs, and imaging findings for Parts B and C."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
36
Recruitment Window Months
90
Consent Approach
Informed consent obtained from adult subjects using subject information sheets and informed consent forms (L1_SIS and ICF Main Adult, Pre-Screening, Pregnancy ICF and country-specific ICFs). Documents provided in multiple languages (English, French, German, Italian, Dutch, Norwegian as indicated by country-specific ICFs). No information on assent or parental consent for minors is provided in the CTIS data.

Methods

  • MyTomorrows digital patient recruitment platform (landing pages, patient navigator scripts) — country-specific (Netherlands, Germany, Italy, Norway, France) materials listed
  • Online advertising — Google advertisements and Facebook advertisements (MyTomorrows Google/Facebook Advertisements) targeting patients
  • Press releases and study-specific press release texts (country-specific)
  • HCP outreach materials — HCP flyer, PI to physician letters, HCP slide decks and HCP websites to engage healthcare professionals
  • Patient-facing materials — patient invitation letters, recruitment flyers, recruitment brochures, posters (country- and language-specific)

Geography

Total Number Of Sites
6
Total Number Of Participants
8

France

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
07-10-2024
Processing Time Days
13
Number Of Sites
2
Number Of Participants
1

Sites

Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Service Endocrinologie-Diabète-Nutrition
Contact Person Name
Laurence Kessler
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Sce Chir Generale & Endocrinienne
Contact Person Name
Francois Pattou
Contact Person Email
francois.pattou@univ-lille.fr

Germany

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
08-10-2024
Processing Time Days
14
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
Department Name
Medizinische Klinik und Poliklinik III/Klinik und Poliklinik f. Viszeral-,Thorax- und Gefäßchirurgie
Contact Person Name
Barbara Ludwig

Italy

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
14-10-2024
Processing Time Days
20
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Ospedale San Raffaele S.r.l.
Department Name
Department of Regenerative Medicine and Transplantation
Contact Person Name
Lorenzo Piemonti
Contact Person Email
piemonti.lorenzo@hsr.it

Netherlands

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
02-10-2024
Processing Time Days
8
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Leiden University Medical Center
Department Name
Leiden University Medical Centre
Contact Person Name
Eelco de Koning
Contact Person Email
e.j.p.de_koning@lumc.nl

Norway

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
03-10-2024
Processing Time Days
9
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Oslo University Hospital HF
Contact Person Name
Trond G Jenssen
Contact Person Email
trond.jenssen@medisin.uio.no

Sponsor

Primary sponsor

Full Name
Vertex Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Investigational products

Investigational Product Name
VX-880 solution for infusion
Active Substance
ZIMISLECEL
Modality
Cell therapy
Routes Of Administration
INTRAPORTAL USE
Route
INTRAPORTAL
Authorisation Status
Investigational (Advanced Therapy IMP - ATIMP)
Starting Dose
0.8 × 10^9 SC-islet cells (single infusion) for Parts B and C (intended dose for infused subjects)
Frequency
Single infusion (per protocol descriptions for Parts B and C)
Maximum Dose
8000000000

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