Back to resultsMELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D) (Meld-ATG)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Anti-Human Thymocyte Immunoglobulin, Rabbit
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1
Eligibility Criteria
The trial is currently only open for recruitment of the following group: 12 - 25 years old Patients aged 5 -11 years old are currently not eligible for the trial.
Inclusion Criteria:
- has given written informed consent to participate; or have a parent or legal guardian provide written informed consent. Individual under the age of consent will be asked to assent to trial participation
- be aged > 5 years to < 25 years at written informed consent/assent
- have been diagnosed with T1d within 3-9 weeks of planned treatment day 1
- have random C-peptide levels > 200 pmol/L measured at screening, as tested centrally
- have 1 or more diabetes-related autoantibody (GADA, IA-2A or ZnT8A) present at screening, as tested centrally
- will be > 6 weeks form last live immunisation at planned treatment day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment
- be willing to comply with intensive diabetes management
Exclusion Criteria:
- Type 2 diabetes
- Evidence of prior or current tuberculosis (TB) infection
- Clinically significant abnormal full blood count (FBC), renal function or liver function at screening
- Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids
- any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any additional immunosuppression
- seropositive for human immunodeficiency virus (HIV),hepatitis B of hepatitis C infection at screening
- positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) based on local testing regimen
- unwilling to use appropriate contraception if sexually active during the trial, from date of written informed consent until completion of the 12-month follow-up visit
- any history of malignancies, other than skin
- current or ongoing use of non-insulin pharmaceuticals that effect glycaemic control
- active participation in another T1D treatment interventional trial in the previous 30 days prior to screening ( excluding treatment with insulin)
- any prior treatment with ATG, Abatacept or Anti-CD3 monoclonal antibody (Anti-CD3)
- known allergy to ATG or to similar products
- any condition, complicating medical issues, or abnormal clinical laboratory results that the investigator judges may adversely affect trial conduct, cause increased risk to the participant, or compromise the trial results
Sites / Locations
- Medical University of GrazRecruiting
- Medical University of ViennaRecruiting
- Universitair Ziekenhuis AntwerpenRecruiting
- Cliniques Universitaires Saint-Luc
- Universitair ziekenhuis BrusselRecruiting
- Universite Libre de BruxellesRecruiting
- Universitaire Ziekenhuizen LeuvenRecruiting
- Herlev University HospitalRecruiting
- Helsinki University Hospital Children and AdolescentsRecruiting
- Hannoversche Kinderheilanstalt Auf der BultRecruiting
- IRCCS Ospedale San RaffaeleRecruiting
- Ospedale Pediatrico Bambino Gesù
- Slaski Uniwersytet Medyczny w Katowicach
- University Medical Centre LjubljanaRecruiting
- Cambridge University Hospitals NHS TrustRecruiting
- The Royal London Hospital - Barts Health NHS TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
placebo
2.5 mg ATG/kg
1.5 mg ATG/kg
0.5 mg ATG/kg
0.1 mg ATG/kg
Arm Description
placebo arm
the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
the next two cohorts of 12 participants will be randomised to placebo, 2.5 mg/Kg, and 2 specified middle ATG total doses in a 1:1:1:1 allocation ratio
The next four cohorts of 15 participants will be randomised to placebo, 2.5 mg/kg and a single selected middle ATG total dose in a 1:1:1 allocation ratio
the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
Outcomes
Primary Outcome Measures
the area under the stimulated C-peptide response curve
Secondary Outcome Measures
the area under the stimulated C-peptide response curve
dry blood spot (DBS) C-peptide measurements
Cluster of differentiation 4 (CD4) positive T cells and Cluster of differentiation 8 (CD8) positive T cells
HbA1c
insulin requirements
The need for insulin (units) on a daily basis
T1D-associated autoantibodies (glutamic acid decarboxylase antibodies (GADA), insulin auto-antibodies (IAA), IA-2 antibodies (IA-2A) and Zinc transporter 8 antibodies (ZnT8A))
The presence of T1D-associated autoantibodies
continuous glucose monitoring (CGM) measurements ( time in range, time above time below)
Full Information
NCT ID
NCT04509791
First Posted
August 7, 2020
Last Updated
June 22, 2023
Sponsor
Universitaire Ziekenhuizen KU Leuven
1. Study Identification
Unique Protocol Identification Number
NCT04509791
Brief Title
MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D)
Acronym
Meld-ATG
Official Title
MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 24, 2020 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study has been set up within the framework of the INNODIA network. INNODIA is a global partnership between 31 academic institutions, 6 industrial partners, a small sized enterprise and 2 patient organizations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes". (www.innodia.eu) The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D).
For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe and UK (United Kingdom), with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with T1D and their families.
The MELD-ATG trial is a phase II, Multi-centre, randomised, double-blind, placebo-controlled, Multi-arm parallel cohort trial.
to investigate the effect of 2.5 mg/kg og ATG on the preservation of stimulated C-peptide at 12 months compared to placebo
to identify the minimally effective dose of ATG that shows an effect on C-peptide when compared to placebo at 12 months
Detailed Description
A phase II, Multi-centre, randomised, double-blind, placebo-controlled, Multi-arm parallel cohort trial.
Randomisation wil be stratified by age. The trial consist of seven cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg.
ATG total dose in a 1:1:1:1 allocation ratio. There will be an initial age step down selection of this cohort with recruitment starting with dose aged 12-25 years and, providing no new safety concerns are raised in the first 10 participants to receive active dose, progressing to all ages (5-25 years) The next two cohorts of 12 participants will be randomised to placebo, 2.5 mg/kg, and 2 specified middle ATG total doses in a 1:1:1:1 allocation ratio.
The next four cohorts of 15 participants will be randomised to placebo, 2.5 mg/kg, and a single selected middle ATG total doses in a 1:1:1 allocation ratio.
This design allows sequential adjustment of the middle doses to be explored following review of all safety and early efficacy data by the Independent Data Monitoring Committee ( IDMC) and Dose Determine Committee (DDC) to seek the minimum effective dose
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
the trial design consists of 7 cohorts, each recruited sequentially, with between 3 and 5 treatment arms ( there will be fewer arms for later cohorts)
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo arm
Arm Title
2.5 mg ATG/kg
Arm Type
Active Comparator
Arm Description
the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
Arm Title
1.5 mg ATG/kg
Arm Type
Active Comparator
Arm Description
the next two cohorts of 12 participants will be randomised to placebo, 2.5 mg/Kg, and 2 specified middle ATG total doses in a 1:1:1:1 allocation ratio
Arm Title
0.5 mg ATG/kg
Arm Type
Active Comparator
Arm Description
The next four cohorts of 15 participants will be randomised to placebo, 2.5 mg/kg and a single selected middle ATG total dose in a 1:1:1 allocation ratio
Arm Title
0.1 mg ATG/kg
Arm Type
Active Comparator
Arm Description
the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
Intervention Type
Drug
Intervention Name(s)
Anti-Human Thymocyte Immunoglobulin, Rabbit
Other Intervention Name(s)
ATG
Intervention Description
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Primary Outcome Measure Information:
Title
the area under the stimulated C-peptide response curve
Time Frame
over the first 2 hours of a mixed meal tolerance test (MMTT) at 12 months post treatment
Secondary Outcome Measure Information:
Title
the area under the stimulated C-peptide response curve
Time Frame
over the first 2 hours of a MMTT at baseline, 3, 6 and 12 months
Title
dry blood spot (DBS) C-peptide measurements
Time Frame
at all observation times
Title
Cluster of differentiation 4 (CD4) positive T cells and Cluster of differentiation 8 (CD8) positive T cells
Time Frame
over 12 months
Title
HbA1c
Time Frame
over 12 months
Title
insulin requirements
Description
The need for insulin (units) on a daily basis
Time Frame
over 12 months
Title
T1D-associated autoantibodies (glutamic acid decarboxylase antibodies (GADA), insulin auto-antibodies (IAA), IA-2 antibodies (IA-2A) and Zinc transporter 8 antibodies (ZnT8A))
Description
The presence of T1D-associated autoantibodies
Time Frame
over 12 months
Title
continuous glucose monitoring (CGM) measurements ( time in range, time above time below)
Time Frame
over 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
has given written informed consent to participate; or have a parent or legal guardian provide written informed consent. Individual under the age of consent will be asked to assent to trial participation
be aged > 5 years to < 25 years at written informed consent/assent
have been diagnosed with T1d within 3-9 weeks of planned treatment day 1
have random C-peptide levels > 200 pmol/L measured at screening, as tested centrally
have 1 or more diabetes-related autoantibody (GADA, IA-2A or ZnT8A) present at screening, as tested centrally
will be > 6 weeks form last live immunisation at planned treatment day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment
be willing to comply with intensive diabetes management
Exclusion Criteria:
Type 2 diabetes
Evidence of prior or current tuberculosis (TB) infection
Clinically significant abnormal full blood count (FBC), renal function or liver function at screening
Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids
any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any additional immunosuppression
seropositive for human immunodeficiency virus (HIV),hepatitis B of hepatitis C infection at screening
positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) based on local testing regimen
unwilling to use appropriate contraception if sexually active during the trial, from date of written informed consent until completion of the 12-month follow-up visit
any history of malignancies, other than skin
current or ongoing use of non-insulin pharmaceuticals that effect glycaemic control
active participation in another T1D treatment interventional trial in the previous 30 days prior to screening ( excluding treatment with insulin)
any prior treatment with ATG, Abatacept or Anti-CD3 monoclonal antibody (Anti-CD3)
known allergy to ATG or to similar products
any condition, complicating medical issues, or abnormal clinical laboratory results that the investigator judges may adversely affect trial conduct, cause increased risk to the participant, or compromise the trial results
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chantal Mathieu, MD,pHD
Phone
+3216346994
Email
chantal.mathieu@uzleuven.be
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Van Ryckeghem, pHD
Phone
+3216342129
Email
MELD-ATG@uzleuven.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
chantal Mathieu, MD,pHD
Organizational Affiliation
Universitaire Ziekenhuizen KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz
City
Graz
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvia Leitgeb
Email
silvia.leitgeb@medunigraz.at
First Name & Middle Initial & Last Name & Degree
Thomas Pieber, Prof. MD
Facility Name
Medical University of Vienna
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Birgit Rami-Merhar
Email
birgit.rami@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Birgit Rami-Merhar, Prof. MD
Facility Name
Universitair Ziekenhuis Antwerpen
City
Antwerp
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rie Braspenning
Email
Rie.Braspenning@uza.be
First Name & Middle Initial & Last Name & Degree
Christophe De Block, Prof. MD
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
Country
Belgium
Individual Site Status
Withdrawn
Facility Name
Universitair ziekenhuis Brussel
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valerie Vandamme
Email
valerie.vandamme@uzbrussel.be
First Name & Middle Initial & Last Name & Degree
Robert Hilbrands, Prof. MD
Facility Name
Universite Libre de Bruxelles
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aïcha Hamouda
Email
aicha.hamouda@erasme.ulb.ac.be
First Name & Middle Initial & Last Name & Degree
Miriam Cnop, Prof. MD
Facility Name
Universitaire Ziekenhuizen Leuven
City
Leuven
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Renka Van Heyste
Email
renka.vanheyste@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Natalie Van den Driessche
Email
natalie.vandendriessche@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Chantal Mathieu, Prof. MD
Facility Name
Herlev University Hospital
City
Herlev
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annette Hillersborg
Email
annette.hillersborg.02@regionh.dk
First Name & Middle Initial & Last Name & Degree
Jesper Johannesen, Prof. MD
Facility Name
Helsinki University Hospital Children and Adolescents
City
Helsinki
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marja Salonen
Email
marja.salonen@helsinki.fi
First Name & Middle Initial & Last Name & Degree
Mari-Anne Pulkkinen, MD
Facility Name
Hannoversche Kinderheilanstalt Auf der Bult
City
Hannöver
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karsten Bode
Email
karsten.bode@hka.de
First Name & Middle Initial & Last Name & Degree
Thomas Danne, Prof. MD
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sabina Martinenghi
Email
martinenghi.sabina@hsr.it
First Name & Middle Initial & Last Name & Degree
Emanuele Bosi, Prof. MD
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annalisa Deodati
Email
annalisa.deodati@opbg.net
First Name & Middle Initial & Last Name & Degree
Stefano Cianfarani, Prof. MD
Facility Name
Slaski Uniwersytet Medyczny w Katowicach
City
Katowice
Country
Poland
Individual Site Status
Withdrawn
Facility Name
University Medical Centre Ljubljana
City
Ljubljana
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brigita Mali
Email
brigita.mali@kclj.si
First Name & Middle Initial & Last Name & Degree
Darja Šmigoc Schweiger
Facility Name
Cambridge University Hospitals NHS Trust
City
Cambridge
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emile Hendriks
Email
aejh6@medschl.cam.ac.uk
First Name & Middle Initial & Last Name & Degree
Emile Hendriks, MD
First Name & Middle Initial & Last Name & Degree
Mark Evans, MD
Facility Name
The Royal London Hospital - Barts Health NHS Trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruben Willemsen
Email
ruben.willemsen@nhs.net
First Name & Middle Initial & Last Name & Degree
Ruben Willemsen, MD
First Name & Middle Initial & Last Name & Degree
Evelien Gevers, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34876434
Citation
Wilhelm-Benartzi CS, Miller SE, Bruggraber S, Picton D, Wilson M, Gatley K, Chhabra A, Marcovecchio ML, Hendriks AEJ, Morobe H, Chmura PJ, Bond S, Aschemeier-Fuchs B, Knip M, Tree T, Overbergh L, Pall J, Arnaud O, Haller MJ, Nitsche A, Schulte AM, Mathieu C, Mander A, Dunger D. Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes. BMJ Open. 2021 Dec 7;11(12):e053669. doi: 10.1136/bmjopen-2021-053669.
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MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D)
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