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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) (Meld-ATG)

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ClinicalTrials.gov Identifier: NCT04509791
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention 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: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 24, 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Placebo Comparator: placebo
placebo arm
Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG

Active Comparator: 2.5 mg ATG/kg
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
Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG

Active Comparator: 1.5 mg ATG/kg
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
Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG

Active Comparator: 0.5 mg ATG/kg
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
Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG

Active Comparator: 0.1 mg ATG/kg
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
Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG




Primary Outcome Measures :
  1. 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 Measures :
  1. 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 ]
  2. dry blood spot (DBS) C-peptide measurements [ Time Frame: at all observation times ]
  3. Cluster of differentiation 4 (CD4) positive T cells and Cluster of differentiation 8 (CD8) positive T cells [ Time Frame: over 12 months ]
  4. HbA1c [ Time Frame: over 12 months ]
  5. insulin requirements [ Time Frame: over 12 months ]
    The need for insulin (units) on a daily basis

  6. T1D-associated autoantibodies (glutamic acid decarboxylase antibodies (GADA), insulin auto-antibodies (IAA), IA-2 antibodies (IA-2A) and Zinc transporter 8 antibodies (ZnT8A)) [ Time Frame: over 12 months ]
    The presence of T1D-associated autoantibodies

  7. continuous glucose monitoring (CGM) measurements ( time in range, time above time below) [ Time Frame: over 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04509791


Contacts
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Contact: Chantal Mathieu, MD,pHD +3216346994 chantal.mathieu@uzleuven.be
Contact: Lisa Van Ryckeghem, pHD +3216342129 MELD-ATG@uzleuven.be

Locations
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Austria
Medical University of Graz Not yet recruiting
Graz, Austria
Contact: Silvia Leitgeb       silvia.leitgeb@medunigraz.at   
Principal Investigator: Thomas Pieber, Prof. MD         
Medical University of Vienna Not yet recruiting
Vienna, Austria
Contact: Birgit Rami-Merhar       birgit.rami@meduniwien.ac.at   
Principal Investigator: Birgit Rami-Merhar, Prof. MD         
Belgium
Universitair Ziekenhuis Antwerpen Not yet recruiting
Antwerp, Belgium
Contact: Rie Braspenning       Rie.Braspenning@uza.be   
Principal Investigator: Christophe De Block, Prof. MD         
Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium
Contact: Paola Gallo       paola.gallo@uclouvain.be   
Principal Investigator: Philippe Lysy, Prof. MD         
Universitair ziekenhuis Brussel Not yet recruiting
Brussels, Belgium
Contact: Ursule Van de Velde       Ursule.VandeVelde@uzbrussel.be   
Principal Investigator: Bart Keymeulen, Prof. MD         
Universite Libre de Bruxelles Recruiting
Brussels, Belgium
Contact: Aïcha Hamouda       aicha.hamouda@erasme.ulb.ac.be   
Principal Investigator: Miriam Cnop, Prof. MD         
Universitaire Ziekenhuizen Leuven Recruiting
Leuven, Belgium
Contact: Renka Van Heyste       renka.vanheyste@uzleuven.be   
Contact: Natalie Van den Driessche       natalie.vandendriessche@uzleuven.be   
Principal Investigator: Chantal Mathieu, Prof. MD         
Denmark
Herlev University Hospital Not yet recruiting
Herlev, Denmark
Contact: Gowthami Gunapalasingham       gowthami.gunapalasingham.01@regionh.dk   
Principal Investigator: Jesper Johannesen, Prof. MD         
Finland
Helsinki University Hospital Children and Adolescents Not yet recruiting
Helsinki, Finland
Contact: Katriina Koski       katriina.koski@helsinki.fi   
Principal Investigator: Mikael Knip, Prof. MD         
Germany
Hannoversche Kinderheilanstalt Auf der Bult Recruiting
Hannöver, Germany
Contact: Karsten Bode       karsten.bode@hka.de   
Principal Investigator: Thomas Danne, Prof. MD         
Italy
IRCCS Ospedale San Raffaele Not yet recruiting
Milano, Italy
Contact: Sabina Martinenghi       martinenghi.sabina@hsr.it   
Principal Investigator: Emanuele Bosi, Prof. MD         
Ospedale Pediatrico Bambino Gesù Not yet recruiting
Roma, Italy
Contact: Annalisa Deodati       annalisa.deodati@opbg.net   
Principal Investigator: Stefano Cianfarani, Prof. MD         
Poland
Slaski Uniwersytet Medyczny w Katowicach Not yet recruiting
Katowice, Poland
Contact: Hanna Szczudło       hanna.szczudlo@sum.edu.pl   
Principal Investigator: Przemyslawa Jarosz-Chobot, Prof. MD         
Slovenia
University Medical Centre Ljubljana Recruiting
Ljubljana, Slovenia
Contact: Brigita Mali       brigita.mali@kclj.si   
Principal Investigator: Darja Šmigoc Schweiger         
United Kingdom
Cambridge University Hospitals NHS Trust Recruiting
Cambridge, United Kingdom
Contact: Emile Hendriks       aejh6@medschl.cam.ac.uk   
Principal Investigator: Emile Hendriks, MD         
Sub-Investigator: Mark Evans, MD         
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
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Principal Investigator: chantal Mathieu, MD,pHD Universitaire Ziekenhuizen Leuven
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Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT04509791    
Other Study ID Numbers: S63466
2019-003265-17 ( EudraCT Number )
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Immunoglobulins
Immunoglobulins, Intravenous
Antibodies
Thymoglobulin
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents