Clinical Trial Results:
Open-Label Study to Evaluate Long Term Safety and Treatment Effect of DiaPep277® in Subjects who Have Completed Study 1001 (EudraCT No.: 2009-015929-37)
Summary
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EudraCT number |
2013-002775-17 |
Trial protocol |
IT CZ HU AT LT ES PL |
Global end of trial date |
02 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Jul 2016
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First version publication date |
16 Jul 2016
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Other versions |
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 |
1010
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01898286 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Andromeda Biotech Ltd.
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Sponsor organisation address |
42 Hayarkon St., Yavne, Israel, 81227
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Public contact |
42 Hayarkon St.
Industrial Area, Yavne 81227, Israel, Andromeda Biotech Ltd., 42 Hayarkon St.
Industrial Area, Yavne 81227, Israel, Andromeda Biotech Ltd., +972 8 9387777,
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Scientific contact |
42 Hayarkon St.
Industrial Area, Yavne 81227, Israel, Andromeda Biotech Ltd., 42 Hayarkon St.
Industrial Area, Yavne 81227, Israel, Andromeda Biotech Ltd., +972 8 9387777,
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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 |
02 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Sep 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Dec 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
This is an extension study to evaluate the safety and tolerability of long-term treatment with DiaPep277® and to determine the long-term treatment effect of DiaPep277® on parameters of metabolic control and on preservation of beta-cell function in subjects who have long exposure to DiaPep277®.
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Protection of trial subjects |
The Guidelines of the World Medical Association Declaration of Helsinki in its revised edition (64th World Medical Association General Assembly, Fortaleza, Brazil, October 2013), the Guidelines of International Conference of Harmonization (ICH) Good Clinical Practice (GCP) (CPMP/ICH/135/95), and the demands of national drug and data protection laws and other applicable regulatory requirements were followed during this study.
This study also conformed to the laws and regulations of the countries in which it was conducted, as well as any applicable guidelines. All personnel involved in the study worked within the confines of the
European Data Protection Directive as interpreted by each country’s laws.
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Background therapy |
- | ||
Evidence for comparator |
Not applicable (Intervention Model: Single Group Assignment) | ||
Actual start date of recruitment |
08 Oct 2013
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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 |
Spain: 3
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Russian Federation: 10
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Country: Number of subjects enrolled |
United States: 13
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Country: Number of subjects enrolled |
Czech Republic: 5
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Country: Number of subjects enrolled |
Germany: 4
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Worldwide total number of subjects |
38
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EEA total number of subjects |
15
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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) |
0
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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) |
38
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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 |
Subjects diagnosed with Type 1 diabetes mellitus up to six months before randomization to Study 1001 (EudraCT No.: 2009-015929-37), from medical sites in the EU, US, Russia, and Israel. | ||||||||||||||
Pre-assignment
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Screening details |
Ninety-nine subjects were screened for the study, 61 subjects failed screening and 38 subjects were enrolled: all 38 enrolled subjects completed the Baseline-Ext Visit (Month 0). The total duration of this study was planned to be up to 26 months: due to the early termination of the study, no subject reached the 9 month visit. | ||||||||||||||
Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
Open-Label
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Arms
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Arm title
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All 1010 Study Subjects treated with DiaPep277® | ||||||||||||||
Arm description |
All subjects enrolled in the 1010 study, whether previously treated with DiaPep277 or placebo in the 1001 study (EudraCT No.: 2009-015929-37). Subjects who completed the 1001 study and maintained clinically significant beta-cell function were offered a 2-year continuation of active treatment, since they were likely to benefit from use of the medication. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
DiaPep277®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for emulsion for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administration of DiaPep277® to subjects previously enrolled in the Phase 3 Study 1001 (EudraCT No.: 2009-015929-37): 1 mg of DiaPep277® subcutaneously in the upper arm at 0, 3, 6, 9, 12, 15, 18, and 21 months, for a total of 8 administrations.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
Treatment with DiaPep277® is expected to be long-term; stopping treatment may result in the eventual loss of the preserved beta-cell function. Indeed, extension of phase 2 studies has shown that subjects who were initially treated with DiaPep277® and maintained their initial beta-cell function, required continuation of treatment, losing beta-cell function if switched to Placebo. These extension studies were too small for the outcome to be statistically significant, but they suggested that continuation of treatment is needed for long-term maintenance of efficacy. Therefore, in this extension study, subjects who completed the 1001 study and maintained clinically significant beta-cell function were offered a 2-year continuation of active treatment, since they were likely to benefit from use of the medication. Sponsor prematurely ended the study hence this report presents the data of subjects assessed until the study end. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All 1010 Study Subjects treated with DiaPep277®
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Reporting group description |
All subjects enrolled in the 1010 study, whether previously treated with DiaPep277 or placebo in the 1001 study (EudraCT No.: 2009-015929-37). Subjects who completed the 1001 study and maintained clinically significant beta-cell function were offered a 2-year continuation of active treatment, since they were likely to benefit from use of the medication. | ||
Subject analysis set title |
DiaPep277® - DiaPep277® group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received DiaPep277® in both 1001 (EudraCT No.: 2009-015929-37) and the current study.
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Subject analysis set title |
Placebo - DiaPep277® group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received Placebo in 1001 (EudraCT No.: 2009-015929-37) and DiaPep277® in the current study
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End point title |
Hypoglycemic events [1] | ||||||||
End point description |
The number of hypoglycemic events recorded by each subject over the course of the study: due to this study's early termination and the submission of an abbreviated CSR, the number of hypoglycemic events of all 38 study subjects were not reported separately by the two subject analysis sets DiaPep277® - DiaPep277® and Placebo-DiaPep277®.
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End point type |
Primary
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End point timeframe |
At early termination visit, up to 25 months.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to the early termination of the study, many of the endpoints described in the protocol could not be adequately assessed and a full SAP was not written. Hypoglycemic events from Continuous Glucose Monitoring System (CGMS) were listed as efficacy parameters: CGMS data were not evaluated |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Glucagon-stimulated C-peptide AUC at Early Termination Visit - Pancreatic Beta-cell Function | ||||||||||||||||
End point description |
Beta-cell function, measured as change in stimulated C-peptide secretion measured 0, 2, 6, 10 and 20 minutes post administration [area under the curve (AUC), 0-20 minutes] at Baseline and the early termination visit (up to 25 months), during a glucagon stimulation test (GST). Change was calculated for each subject by substracting the baseline AUC value (defined as the last non-missing assessment prior to first dose in the 1010 study but after the end of study 1001 - EudraCT No.: 2009-015929-37) from the early termination visit AUC.
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End point type |
Secondary
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End point timeframe |
Baseline and Early Termination Visit, up to 25 months.
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Notes [2] - Mean change from Baseline-Ext [3] - Mean change from Baseline-Ext [4] - Mean change from Baseline-Ext |
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No statistical analyses for this end point |
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End point title |
Glycemic Control | ||||||||
End point description |
Change From Baseline in % HbA1c
Due to this study's early termination and the submission of an abbreviated CSR, the number of hypoglycemic events of all 38 study subjects were not reported separately by the two subject analysis sets DiaPep277® - DiaPep277® and Placebo-DiaPep277®.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and Early Termination Visit, Up to 25 Months
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Daily Insulin Dose, Per kg Body Weight, at Early Termination Visit | ||||||||
End point description |
Due to this study's early termination and the submission of an abbreviated CSR, the number of hypoglycemic events of all 38 study subjects were not reported separately by the two subject analysis sets DiaPep277® - DiaPep277® and Placebo-DiaPep277®.
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End point type |
Other pre-specified
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End point timeframe |
Baseline and Early Termination Visit, up to 25 months.
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AE) data were collected from the time of subject enrollment through each subject's early termination visit.
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Adverse event reporting additional description |
Due to this study's early termination and the submission of an abbreviated CSR, the AE of all 38 study subjects were not reported separately by the two study arms of DiaPep277®-DiaPep277® and Placebo-DiaPep277®.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
All 1010 Study Subjects treated with DiaPep277®
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Reporting group description |
Treatment with DiaPep277® is expected to be long-term; stopping treatment may result in the eventual loss of the preserved beta-cell function. Indeed, extension of phase 2 studies has shown that subjects who were initially treated with DiaPep277® and maintained their initial beta-cell function, required continuation of treatment, losing beta-cell function if switched to Placebo. These extension studies were too small for the outcome to be statistically significant, but they suggested that continuation of treatment is needed for long-term maintenance of efficacy. Therefore, in this extension study, subjects who completed the 1001 study and maintained clinically significant beta-cell function were offered a 2-year continuation of active treatment, since they were likely to benefit from use of the medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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20 Jan 2014 |
The original protocol dated 18 June 2013, Version 1.0, was amended once during the study with the protocol version 2.0 (dated 20 January 2014).
The major changes made in Protocol Version 2.0 are given below:
- Modified the study title and study timelines.
- Revised text on efficacy parameters and added a new efficacy parameter of CGMS in a subset of subjects.
- Clarified text on solvent emulsion that would be supplied.
- Added text for abnormal LFTs.
- Added text in the study assessment schedule regarding Baseline-Ext visit and CGMS.
- Added text on additional laboratory tests on serum antibodies.
- Revised text in statistical methods.
- Added text regarding informed consent process for optional CGMS. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
The study was prematurely terminated by Sponsor on 08Sep2014 and many of the endpoints described in the protocol could not be adequately assessed and a full SAP was not written (please refer to the above global Interruptions section). |