Clinical Trial Results:
GPPAD-POInT (Global Platform of Autoimmune Diabetes – Primary Oral Insulin Trial)
Oral Insulin Therapy for Prevention of Autoimmune Diabetes
A study of the Global Platform for the Prevention of Autoimmune Diabetes
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Summary
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EudraCT number |
2017-003088-36 |
Trial protocol |
SE GB PL DE BE |
Global end of trial date |
28 Jun 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Dec 2025
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First version publication date |
04 Dec 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GPPAD-03-POInT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03364868 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Technische Universität München, School of Medicine
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Sponsor organisation address |
Ismaninger Strasse 22, München, Germany, 81675
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Public contact |
Prof. Dr. Anette-G. Ziegler, Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München , +49 8931872896, anette-g.ziegler@helmholtz-muenchen.de
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Scientific contact |
Prof. Dr. Anette-G. Ziegler, Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München , +49 8931872896, anette-g.ziegler@helmholtz-muenchen.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Jun 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Jun 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
As part of the safety assessment , blood glucose was monitored before (-10 minutes) and at 30, 60 and 120 minutes after study drug intake at baseline, and at the visits 2, 4 and 8 months.
Adverse events were recorded and assessed until 60 days after end of treatment.
Local anesthetics (EMLA)was used to reduce pain during blood draws.
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Background therapy |
No background therapy | ||
Evidence for comparator |
No comparators | ||
Actual start date of recruitment |
07 Feb 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 504
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Country: Number of subjects enrolled |
Belgium: 80
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Country: Number of subjects enrolled |
Poland: 242
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Country: Number of subjects enrolled |
Sweden: 173
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Country: Number of subjects enrolled |
United Kingdom: 51
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Worldwide total number of subjects |
1050
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EEA total number of subjects |
999
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
1050
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Potential study subjects were identified through the GPPAD-02 study testing for type 1 diabetes risk in infancy. In the GPPAD-02 study, testing for genetic risk of T1D was offered either at delivery (cord blood), together with the regular newborn screening, or at a pediatric baby-visit with collection of blood using GPPAD-02 filter paper cards. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Infants were tested for genetic risk of T1D based on risk scores derived from SNPs that defined HLA DR3, HLA DR4, and HLA DQ8 alleles, as well as SNPs from HLA class I and non-HLA T1D susceptibility genes, and from HLA class II protective alleles | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
The IMP management including the blinding was done by a separate Interactive Web Remote System (IWRS).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
The reference placebo (filling substance only: microcrystalline cellulose) is identical in appearance to the active medication. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Microcrystalline Cellulose
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
The reference placebo (filling substance only: microcrystalline cellulose) is identical in appearance to the active medication.
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Arm title
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Oral Insulin | |||||||||||||||||||||||||||
Arm description |
Daily oral insulin / dose escalation: 7.5 mg for 2 months, followed by 22.5 mg for 2 months, followed by 67.5 mg until age 3.0 years | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Oral Insulin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Active ingredient:
Insulin provided as bulk human crystals filled in capsules.
Formulation of 7.5 mg, 22.5 mg and 67.5 mg insulin and microcrystalline cellulose as filling substance.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
The reference placebo (filling substance only: microcrystalline cellulose) is identical in appearance to the active medication. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oral Insulin
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Reporting group description |
Daily oral insulin / dose escalation: 7.5 mg for 2 months, followed by 22.5 mg for 2 months, followed by 67.5 mg until age 3.0 years | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis set (ITT)
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Intention to treat: The intention-to-treat population includes all randomized children who received at least one dose of study medi-cation, according to the treatment they were randomized to receive
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Subject analysis set title |
Per protocol population
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per-protocol population will be defined as all randomized children who were administered at least 85% of the expected number of capsules until either age 3 years or, for children who reached the study primary outcome prior to age 3 years, until the study visit when the child was defined as primary outcome positive (two or more islet au-toantibodies or diabetes).
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Subject analysis set title |
Full analysis set modified for primary outcome
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Subject analysis set type |
Modified intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The mITT population includes all randomized participants who received at least one dose of study medication, excluding those with two or more persistent confirmed islet autoantibodies at baseline. This population was used for the analysis of the primary outcome, in accordance with the Statistical Analysis Plan.
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Subject analysis set title |
Safety analysis
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This population includes all randomized participants who received at least one dose of the investigational medicinal product (IMP). Safety outcomes were assessed during the treatment period and up to 60 days after treatment discontinuation. All adverse and serious adverse events were evaluated according to standard reporting guidelines.
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
The reference placebo (filling substance only: microcrystalline cellulose) is identical in appearance to the active medication. | ||
Reporting group title |
Oral Insulin
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Reporting group description |
Daily oral insulin / dose escalation: 7.5 mg for 2 months, followed by 22.5 mg for 2 months, followed by 67.5 mg until age 3.0 years | ||
Subject analysis set title |
Full analysis set (ITT)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Intention to treat: The intention-to-treat population includes all randomized children who received at least one dose of study medi-cation, according to the treatment they were randomized to receive
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Subject analysis set title |
Per protocol population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol population will be defined as all randomized children who were administered at least 85% of the expected number of capsules until either age 3 years or, for children who reached the study primary outcome prior to age 3 years, until the study visit when the child was defined as primary outcome positive (two or more islet au-toantibodies or diabetes).
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Subject analysis set title |
Full analysis set modified for primary outcome
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The mITT population includes all randomized participants who received at least one dose of study medication, excluding those with two or more persistent confirmed islet autoantibodies at baseline. This population was used for the analysis of the primary outcome, in accordance with the Statistical Analysis Plan.
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Subject analysis set title |
Safety analysis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
This population includes all randomized participants who received at least one dose of the investigational medicinal product (IMP). Safety outcomes were assessed during the treatment period and up to 60 days after treatment discontinuation. All adverse and serious adverse events were evaluated according to standard reporting guidelines.
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End point title |
Development of persistent confirmed multiple beta-cell autoantibodies or diagnosis of type 1 diabetes | |||||||||
End point description |
The primary outcome was the development of two or more islet autoantibodies, which were
defined as confirmed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA),
insulinoma-associated antigen-2 (IA-2A), or zinc transporter-8 (ZnT8A) in two consecutive
samples, and a second autoantibody in at least one sample . Participants who
developed diabetes prior to two or more islet autoantibodies were also considered to have
reached the primary outcome.
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End point type |
Primary
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End point timeframe |
The primary endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1 diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Two or More Islet AAB or Diabetes | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ratio by study arm.
The primary analysis evaluated the time from randomisation to the development of persistent confirmed multiple beta-cell autoantibodies or clinical diagnosis of type 1 diabetes
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
1048
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||
P-value |
= 0.56 | |||||||||
Method |
Wald-test | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.12
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.76 | |||||||||
upper limit |
1.67 | |||||||||
Variability estimate |
Standard deviation
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| Notes [1] - Superiority analysis was chosen to test whether oral insulin reduces the incidence of beta-cell autoimmunity compared to placebo. |
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End point title |
Primary Outcome in the Sensitivity Analysis | |||||||||
End point description |
The primary outcome was the development of two or more islet autoantibodies, which were
defined as confirmed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA),
insulinoma-associated antigen-2 (IA-2A), or zinc transporter-8 (ZnT8A) in two consecutive
samples, and a second autoantibody in at least one sample . Participants who
developed diabetes prior to two or more islet autoantibodies were also considered to have
reached the primary outcome.
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End point type |
Primary
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End point timeframe |
The primary endpoint was assessed from randomization (age 4-7 months) until diagnosis of type 1 diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Sensitivity Analysis Dataset | |||||||||
Statistical analysis description |
Events, cumulative incidence and Hazard-Ration by study arm in the sensitivity analysis set.
Children, who have two or more islet autoantibodies at baseline, are included in a sensitivity analysis of the primary outcome.
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
1049
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.5 | |||||||||
Method |
Wald-test | |||||||||
Parameter type |
Log hazard ratio | |||||||||
Point estimate |
1.14
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.77 | |||||||||
upper limit |
1.7 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Primary Outcome: per Protocol Population Dataset | |||||||||
End point description |
The primary outcome was the development of two or more islet autoantibodies, which were
defined as confirmed autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA),
insulinoma-associated antigen-2 (IA-2A), or zinc transporter-8 (ZnT8A) in two consecutive
samples, and a second autoantibody in at least one sample . Participants who
developed diabetes prior to two or more islet autoantibodies were also considered to have
reached the primary outcome.
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End point type |
Primary
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End point timeframe |
The primary endpoint was assessed from randomization (age4-7 months) until diagnosis of type 1 diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Per Protocol Population Dataset | |||||||||
Statistical analysis description |
Events, cumulative incidence and Hazard Ration by study arm in the per protocol population dataset.
The per-protocol population was defined as all randomized children who were administered at least 85% of the expected number of capsules until either age 3 years or, for children who reached the study primary outcome prior to age 3 years, until the study visit when the child was defined as primary outcome positive (two or more islet autoantibodies or diabetes).
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
909
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.72 | |||||||||
Method |
Wald-test | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.08
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.72 | |||||||||
upper limit |
1.62 | |||||||||
Variability estimate |
Standard deviation
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End point title |
One or more islet autoantibody | |||||||||
End point description |
Time from randomisation to development of any persistent confirmed islet autoantibody (IAA, GADA, IA-2A, or ZnT8A), confirmed in two consecutive samples
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End point type |
Secondary
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End point timeframe |
The secondary endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
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Statistical analysis title |
One or more islet Autoantibodies | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ratio by study arm
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
1049
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.25 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.23
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.86 | |||||||||
upper limit |
1.76 | |||||||||
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End point title |
Persistent confirmed IAA | |||||||||
End point description |
The secondary outcome was the elapsed time from random treatment assignment to the development of persistent confirmed IAA.
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End point type |
Secondary
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End point timeframe |
The secondary endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Persistent Confirmed IAA | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ratio
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
1042
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.28 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.24
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.84 | |||||||||
upper limit |
1.85 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Persistent confirmed GADA | |||||||||
End point description |
The secondary outcome was the elapsed time from random treatment assignment to the development of persis-tent confirmed GADA.
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End point type |
Secondary
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End point timeframe |
The secondary endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Persistent Confirmed GADA | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ratio by study arm
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Comparison groups |
Placebo v Oral Insulin
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Number of subjects included in analysis |
1047
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.33 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.24
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.8 | |||||||||
upper limit |
1.91 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Diabetes or dysglycemia | |||||||||
End point description |
The secondary outcome was the elapsed time from random treatment assignment to the development of persis-tent dysglycemia or diabetes.
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End point type |
Secondary
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End point timeframe |
The secondary endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
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Statistical analysis title |
Diabetes or dysglycemia | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ration by study arm
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Comparison groups |
Oral Insulin v Placebo
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Number of subjects included in analysis |
1049
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.34 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.74
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.4 | |||||||||
upper limit |
1.37 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Clinical Diabetes (Exploratory Outcome) | |||||||||
End point description |
Exploratory outcome was the elapsed time from random treatment assignment to the development of clinical diabetes.
In children who did not reach the exploratory outcome, the elapsed time is the time from random treatment as-signment to the date of last contact .
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End point type |
Other pre-specified
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End point timeframe |
The exploratory endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
|
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|
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Statistical analysis title |
Clinical Diabetes (Exploratory Outcome) | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ratio by study arm
|
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Comparison groups |
Placebo v Oral Insulin
|
|||||||||
Number of subjects included in analysis |
1049
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.32 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.74
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.4 | |||||||||
upper limit |
1.36 | |||||||||
Variability estimate |
Standard deviation
|
|||||||||
|
||||||||||
End point title |
Progression from Primary Outcome to Diabetes (Exploratory Outcome) | |||||||||
End point description |
Exploratory outcome was the elapsed time from the date of primary outcome to the development of clinical dia-betes.
In children who did not reach the exploratory outcome, the elapsed time is the time from the date of primary out-come to the date of last contact.
|
|||||||||
End point type |
Other pre-specified
|
|||||||||
End point timeframe |
The exploratory endpoint was assessed from randomization (age 4–7 months) until diagnosis of type 1
diabetes or up to 54 months after end of treatment
|
|||||||||
|
||||||||||
Statistical analysis title |
Progression from Primary Outcome to Diabetes | |||||||||
Statistical analysis description |
Events, 5-year cumulative incidence and Hazard Ration by study arm
|
|||||||||
Comparison groups |
Placebo v Oral Insulin
|
|||||||||
Number of subjects included in analysis |
98
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.048 | |||||||||
Method |
Logrank | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.54
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.29 | |||||||||
upper limit |
1.01 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were documented throughout the treatment period and for an additional 60 days following the last administration of the investigational medicinal product
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Adverse event reporting additional description |
AEs were reported via eCRF.
Serious adverse events (SAEs) were reviewed and assessed by an external safety manager and reported
to authorities where appropriate.
The evaluation of safety and tolerability included all children who received at least one dose of the investigational product.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
|
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
The reference placebo (filling substance only: microcrystalline cellulose) was identical in appeareance to active IMP | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oral Insulin
|
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Reporting group description |
Daily oral insulin capsules: / dose escalation 7.5 mg for 2 months followed by 22.5 mg for 2 months and 67.5mg followed until age 3.0 years | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
03 Dec 2018 |
Update IMPD and optimized manufacturing process |
||
11 Feb 2022 |
Protocol Version 3.0 to Version 4.0
The amendment relates to the study duration (accrual was shorter than projected), a recalculation of power, and the interim analysis.
In the original POINT protocol, study duration was estimated to last 7 years (including 3.5 years accrual, and 3.5 years follow-up, LPLV projected January 2025), and power was calculated accordingly. However enrollment was shorter and thus the study duration would be ~6.5 years (including 3.17 years accrual, and 3.25 years follow-up, LPLV June 2024).
The statistician performed a new power calculation and confirmed that based on the true number of events and the current drop out rate, we still would have over 80% power despite a reduction of a median of 5 months observation time if we also drop the interim analysis |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/41237794 |
|||
