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| Name | Class |
|---|---|
| Helmholtz Zentrum München | INDUSTRY |
| University Hospital Carl Gustav Carus | OTHER |
| Kinderkrankenhaus auf der Bult | OTHER |
| Skane University Hospital |
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The GPPAD-POInT Study is designed as a randomized, placebo-controlled, double blind, multicentre, multinational primary prevention phase IIb study aiming to induce immune tolerance to beta-cell autoantigens through regular exposure to oral insulin for a period of 29 to 32 months. The hypothesis is that regular exposure to oral insulin throughout the period in life where beta-cell autoimmunity usually initiates will tolerize against insulin and train the body's immune system to recognize the treatment product without reacting adversely to it in a manner seen in children who develop T1D. This immune tolerance induction therapy would reduce the likelihood of beta-cell autoimmunity. The study objective is to determine whether daily administration of oral insulin from age 4 months - 7 months until age 3.00 years to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies and diabetes in childhood.
The GPPAD-POInT-Study aims to determine whether daily administration of oral insulin to children from age 4 months - 7 months with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies and diabetes in childhood. The purpose of the GPPAD-POInT-Study is to induce immune tolerance to beta-cell autoantigens through regular exposure to oral insulin for a period of 29 to 32 months. Together with the results of the Pre-POINT-Early Study, this phase IIb study aims to investigate and consolidate the findings from the pilot Pre-POINT Study, namely safety and immune efficacy at a daily dose of 67.5 mg oral insulin. Since babies and young children will be tested in the GPPAD-POInT-Study, the 67.5 mg dose will be reached by dose escalation starting at 7.5 mg for 2 months, followed by exposure to 22.5 mg for 2 months, and reaching the desired 67.5 mg dose. The GPPAD-POInT-Study aims to recruit 1040 children into the trial.
The active substance for oral application is human insulin. Oral Insulin will be applied as a capsule containing 7.5, 22.5 and 67.5 mg of the active substance together with filling substance microcrystalline cellulose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| oral insulin capsule (dose escalation using 3 dose strengths) | Experimental | Dose 1 is 7.5 mg rH-insulin crystals; dose 2 is 22.5 mg rH-insulin crystals; dose 3 is 67.5 mg rH-insulin crystals. The insulin crystals are formulated together with filling substance (microcrystalline cellulose to a total weight of 200 mg) and contained in hard gelatine capsules. The study treatment will be given orally. |
|
| Placebo capsule | Placebo Comparator | Daily treatment with placebo capsules containing filling substance (microcrystalline cellulose). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Insulin | Drug | treatment starting at 4 months - 7 months until age 3.0 years; dose escalation scheme: daily treatment with 7.5 mg or placebo for 2 months; increasing to daily treatment with 22.5 mg or placebo for the following 2 months; increasing to daily treatment with 67.5 mg or placebo until the end of the treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| The development of persistent confirmed multiple beta-cell autoantibodies | development of persistent confirmed multiple beta-cell autoantibodies (defined as confirmed IAA, confirmed GADA, confirmed IA-2A, or confirmed ZnT8A in two consecutive samples, AND a confirmed second antibody from these four antibodies in one sample. | elapsed time from treatment assignment (baseline) to first positive sample visit (>2 beta-cell antibodies) in children who develop persistent confirmed multiple beta-cell antibodies. Primary outcome can develop any time up to last study visit at 7.5 yrs |
| The development of diabetes | OGTT criteria or clinical criteria for diabetes as defined by the American Diabetes Association (ADA). | elapsed time from random treatment assignment (baseline) to the development diabetes (date of diagnosis). This primary outcome measure can develop any time during treatment or follow-up period up to the last study visit at 7.5 years of age |
| Measure | Description | Time Frame |
|---|---|---|
| Any persistent confirmed beta-cell autoantibody or diabetes | At least one confirmed autoantibody, in two consecutive samples, including GADA, IA-2A, IAA, ZnT8A, or TS7A, or diabetes as defined by the American Diabetes Association (ADA). | elapsed time from treatm. assignm. (baseline) to 1st pos. sample for >1 beta-cell antibody in children who developed persist. confirm. beta-cell antibodies OR diabetes onset, whichever is first. outcome can develop any time up to last visit at 7.5 yr |
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Inclusion Criteria:
1. Infant between the ages of 4 months and 7 months at the time of randomization.
2. A high genetic risk (>10%) to develop beta-cell autoantibodies by age 6 years:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Leuven, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium | Leuven | 3000 | Belgium | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41237794 | Derived | Ziegler AG, Achenbach P, Weiss A, Berner R, Casteels K, Elding Larsson H, Haupt F, Hommel A, Jacobs A, Kordonouri O, Lundgren M, Oltarzewski M, Pfirrmann M, Snape MD, Szypowska A, Todd JA, Vatish M, von dem Berge T, Winkler C, Bonifacio E; GPPAD-POInT Study Group. Efficacy of once-daily, high-dose, oral insulin immunotherapy in children genetically at risk for type 1 diabetes (POInT): a European, randomised, placebo-controlled, primary prevention trial. Lancet. 2025 Nov 29;406(10519):2564-2576. doi: 10.1016/S0140-6736(25)01726-X. Epub 2025 Nov 11. | |
| 34091488 |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| OTHER |
| Universitaire Ziekenhuizen KU Leuven | OTHER |
| Medical University of Warsaw | OTHER |
| University of Oxford, Clinical Vaccine Research and Immunisation Education | UNKNOWN |
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|
| Placebo | Other | treatment starting at age 4 months - 7 months until age 3.0 years; daily treatment with insulin or placebo capsules containing filling substance (microcrystalline cellulose). |
|
| Persistent confirmed IAA. | Confirmed IAA in two consecutive samples. | elapsed time from treatment assignment (baseline) to first sample that is positive for IAA in children who develop persistent confirmed IAA. Outcome can develop any time during treatment or follow-up period up to the last study visit at 7.5 years of age. |
| Persistent confirmed GADA. | Confirmed GADA in two consecutive samples. | elapsed time from treatment assignment (baseline) to the first sample that is positive for GADA in children who develop persistent confirmed GADA. Outcome can develop any time up to the last study visit at 7.5 years of age |
| Abnormal glucose tolerance (AGT) defined by dysglycemia or diabetes. | Dysglycemia is defined as impaired fasting plasma glucose of ≥110 mg/dL (6.1 mmol/L), or impaired 2-hour glucose of ≥140 mg/dL (7.8 mmol/L), or high glucose levels at intermediate time points on OGTT (30, 60, 90 min) levels of ≥200mg/dL (11.1 mmol/L)). Diabetes is defined according to the criteria of the American Diabetes Association (ADA). | elapsed time from treatment assignment to the date at which abnormal glucose tolerance or diabetes is diagnosed. Outcome can develop any time up to the last study visit at 7.5 years of age |
| Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany |
| Munich |
| Bavaria |
| 80804 |
| Germany |
| AUF DER BULT, Kinder- und Jugendkrankenhaus, Hanover, Germany | Hanover | Lower Saxony | 30173 | Germany |
| Klinik und Poliklinik f. Kinder und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, CRTD/DFG-Forschungszentrum für Regenerative Therapien, Dresden, Germany | Dresden | Saxony | 01307 | Germany |
| Medical University of Warsaw, Department of Paediatrics, Warsaw, Poland | Warsaw | 00-001 | Poland |
| Lund University Dep. of Clinical Sciences Malmo, Skane University Hospital SUS, University Hospital MAS, Malmo, Sweden | Malmö | 202 13 | Sweden |
| Department of Paediatrics Clinical Vaccine Research and Immunisation Education, Children's Hospital, Headington, Oxford, UK | Oxford | OX3 9DU | United Kingdom |
| Derived |
| Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648. |
| 31256036 | Derived | Ziegler AG, Achenbach P, Berner R, Casteels K, Danne T, Gundert M, Hasford J, Hoffmann VS, Kordonouri O, Lange K, Elding Larsson H, Lundgren M, Snape MD, Szypowska A, Todd JA, Bonifacio E; GPPAD Study group. Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol. BMJ Open. 2019 Jun 28;9(6):e028578. doi: 10.1136/bmjopen-2018-028578. |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |