Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 60 of 330 for:    C-peptide | "Diabetes Mellitus, Insulin-Dependent"

Efficacy and Safety Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Adults (DIA-AID2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01103284
Recruitment Status : Completed
First Posted : April 14, 2010
Results First Posted : May 26, 2016
Last Update Posted : May 26, 2016
Sponsor:
Information provided by (Responsible Party):
Andromeda Biotech Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: DiaPep277
Drug: Placebo
Enrollment 475
Recruitment Details Patients newly diagnosed with Type 1 diabetes were recruited at medical centers in the US, EU, Argentina, and Israel.
Pre-assignment Details  
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Period Title: Overall Study
Started 236 239
Treated 236 238
At Least One Post-baseline Visit (FAS) 233 [1] 235 [2]
Completed 194 195
Not Completed 42 44
Reason Not Completed
Death             2             0
Lost to Follow-up             9             10
Pregnancy             3             1
Protocol Violation             12             5
Adverse Event             0             5
Withdrawal by Subject             14             18
Dermal Hypersensitivity             0             1
Termination by the Sponsor             0             1
Not described             2             1
Missing CRF entries for study completion             0             2
[1]
Patients reaching this milestone were included in the Full Analysis Set (FAS) population
[2]
Patients reaching this milestone were included in the Full Analysis Set (FAS)
Arm/Group Title DiaPep277 Placebo Total
Hide Arm/Group Description

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Total of all reporting groups
Overall Number of Baseline Participants 236 238 474
Hide Baseline Analysis Population Description
All patients randomized into the study are included in presentation of baseline results
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 236 participants 238 participants 474 participants
28.7  (6.75) 28.5  (6.56) 28.6  (6.65)
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 236 participants 238 participants 474 participants
27.0
(20 to 45)
27.0
(20 to 45)
27.0
(20 to 45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 236 participants 238 participants 474 participants
Female
79
  33.5%
73
  30.7%
152
  32.1%
Male
157
  66.5%
165
  69.3%
322
  67.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 236 participants 238 participants 474 participants
Caucasian 224 225 449
Hispanic 6 6 12
Black 3 4 7
Oriental 1 1 2
Asian 1 0 1
Other 0 2 2
Unknown 1 0 1
Daily Insulin Dose  
Mean (Standard Deviation)
Unit of measure:  IU/kg/day
Number Analyzed 236 participants 238 participants 474 participants
0.305  (0.1587) 0.317  (0.1649) 0.311  (0.1618)
Fasting C-Peptide  
Mean (Standard Deviation)
Unit of measure:  nmol/L
Number Analyzed 236 participants 238 participants 474 participants
0.388  (0.1473) 0.407  (0.1731) 0.398  (0.1609)
1.Primary Outcome
Title Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months
Time Frame Baseline and 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description:

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Overall Number of Participants Analyzed 233 235
Mean (Standard Error)
Unit of Measure: nmol*min/L
-5.20  (0.27) -4.83  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DiaPep277, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments The a priori threshold for statistical significance was 0.05
Method Mixed Models Analysis
Comments The Mixed-Effect Model Repeated Measure (MMRM) was adjusted for the following baseline covariates: age, C-peptide, insulin dose by body weight and AUC
2.Secondary Outcome
Title Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7%
Hide Description The percentage of subjects achieving good glycemic control, i.e. an HbA1c <7% at study end (Month 25). If HbA1c was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with an HbA1c ≤ 7% at study end.
Time Frame 24 and 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit.
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description:

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Overall Number of Participants Analyzed 233 235
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
47
(40 to 54)
47
(40 to 55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DiaPep277, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments A priori threshold for statistical significance was 0.05
Method Mixed Models Analysis
Comments The MMRM model was adjusted for the following covariates: age, Baseline C-peptide, Baseline insulin dose adjusted for body weight, and Baseline AUC.
3.Secondary Outcome
Title Frequency of Hypoglycemic Events
Hide Description Total number of days with at least one hypoglycemic event recorded
Time Frame Baseline to 25 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description:

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Overall Number of Participants Analyzed 233 235
Measure Type: Number
Unit of Measure: days
1955 3264
4.Secondary Outcome
Title Mean Number of Days With at Least One Hypoglycemic Event
Hide Description [Not Specified]
Time Frame Baseline to 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description:

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Overall Number of Participants Analyzed 233 235
Mean (Standard Error)
Unit of Measure: days
13.0  (2.3) 35.4  (7.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DiaPep277, Placebo
Comments The number of hypoglycemia events during the study was analyzed using a negative binomial regression model, with number of events as the dependent variable, and treatment, age, baseline daily insulin dose, and baseline C-peptide as covariates. The log of duration in the study for each patient was used as an offset variable in the model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments Standard multiple imputation was used to predict the number and timing of hypoglycemic events after discontinuing the study for subjects who did not remain in the study until Month 25.
Method negative binomial regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
-0.02 to 0.79
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study
Hide Description Percentage of subjects requiring a daily insulin dose ≤ 0.5 IU/kg at end of study (25 Months). If insulin dose was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with a daily insulin dose ≤ 0.5 IU/kg at study end.
Time Frame 24 and 25 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) All subjects randomized who had a baseline visit and at least one scheduled post-baseline visit.
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description:

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

Overall Number of Participants Analyzed 233 235
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
63
(57 to 69)
57
(50 to 63)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DiaPep277, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.44
Comments The a priori threshold for statistical significance was 0.05
Method Mixed Models Analysis
Comments The MMRM model was adjusted for the following covariates: age, Baseline C-peptide, Baseline insulin dose adjusted for body weight, and Baseline AUC
Time Frame AE data were collected from the time of subject enrollment through one month after the final product administrations (Total of 25 months after first study product administration)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DiaPep277 Placebo
Hide Arm/Group Description

Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

DiaPep277: 1.0 mg dose in 0.5 mL of solution

Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.

Placebo: 40 mg mannitol in 0.5 mL of solution.

Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

All-Cause Mortality
DiaPep277 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DiaPep277 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   15/236 (6.36%)   10/238 (4.20%) 
Blood and lymphatic system disorders     
Lymphadenitis * 1  0/236 (0.00%)  1/238 (0.42%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/236 (0.42%)  0/238 (0.00%) 
Duodenal ulcer hemorrhage * 1  1/236 (0.42%)  0/238 (0.00%) 
Incarcerated inguinal hernia * 1  1/236 (0.42%)  0/238 (0.00%) 
Anal fistula * 1  0/236 (0.00%)  1/238 (0.42%) 
Infections and infestations     
Meningitis viral * 1  1/236 (0.42%)  0/238 (0.00%) 
Pneumonia * 1  1/236 (0.42%)  0/238 (0.00%) 
Tick-borne viral encephalitis * 1  1/236 (0.42%)  0/238 (0.00%) 
Tonsillitis Streptococcal * 1  1/236 (0.42%)  0/238 (0.00%) 
Sialoadenitis * 1  0/236 (0.00%)  1/238 (0.42%) 
Injury, poisoning and procedural complications     
Meniscus inury * 1  1/236 (0.42%)  0/238 (0.00%) 
multiple injuries * 1  0/236 (0.00%)  1/238 (0.42%) 
Metabolism and nutrition disorders     
Diabetic ketoacidosis * 1  2/236 (0.85%)  0/238 (0.00%) 
Hypoglycemia * 1  1/236 (0.42%)  3/238 (1.26%) 
Diabetes mellitus inadequate control * 1  1/236 (0.42%)  0/238 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle disorder * 1  0/236 (0.00%)  1/238 (0.42%) 
Sympathetic posterior cervical syndrome * 1  0/236 (0.00%)  1/238 (0.42%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign muscle neoplasm * 1  0/236 (0.00%)  1/238 (0.42%) 
Nervous system disorders     
Hypoglycemic seizure * 1  1/236 (0.42%)  0/238 (0.00%) 
Loss of Consciousness * 1  0/236 (0.00%)  1/238 (0.42%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous * 1  1/236 (0.42%)  0/238 (0.00%) 
Psychiatric disorders     
Depression * 1  0/236 (0.00%)  1/238 (0.42%) 
Respiratory, thoracic and mediastinal disorders     
Nasal septum deviation * 1  1/236 (0.42%)  0/238 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
DiaPep277 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   171/236 (72.46%)   172/238 (72.27%) 
Blood and lymphatic system disorders     
Blood and lymphatic system disorders * 1  8/236 (3.39%)  10/238 (4.20%) 
Cardiac disorders     
Cardiac disorders * 1  8/236 (3.39%)  6/238 (2.52%) 
Endocrine disorders     
Hypothyroidism * 1  2/236 (0.85%)  5/238 (2.10%) 
Eye disorders     
Eye disorders * 1  4/236 (1.69%)  6/238 (2.52%) 
Gastrointestinal disorders     
Nausea * 1  9/236 (3.81%)  13/238 (5.46%) 
Diarrhea * 1  9/236 (3.81%)  7/238 (2.94%) 
Abdominal Pain * 1  5/236 (2.12%)  6/238 (2.52%) 
Toothache * 1  5/236 (2.12%)  6/238 (2.52%) 
Abdominal pain upper * 1  5/236 (2.12%)  4/238 (1.68%) 
vomiting * 1  4/236 (1.69%)  7/238 (2.94%) 
General disorders     
Injection site pain * 1  20/236 (8.47%)  18/238 (7.56%) 
Asthenia * 1  3/236 (1.27%)  6/238 (2.52%) 
Fatigue * 1  3/236 (1.27%)  5/238 (2.10%) 
Hepatobiliary disorders     
Hepatobiliary Disorders * 1  1/236 (0.42%)  5/238 (2.10%) 
Immune system disorders     
Immune system disorders * 1  6/236 (2.54%)  6/238 (2.52%) 
Infections and infestations     
Nasopharyngitis * 1  52/236 (22.03%)  60/238 (25.21%) 
Upper respiratory tract infection * 1  18/236 (7.63%)  13/238 (5.46%) 
Influenza * 1  15/236 (6.36%)  17/238 (7.14%) 
Sinusitis * 1  10/236 (4.24%)  4/238 (1.68%) 
Gastroenteriitis * 1  7/236 (2.97%)  9/238 (3.78%) 
Urinary tract infection * 1  7/236 (2.97%)  8/238 (3.36%) 
Bronchitis * 1  7/236 (2.97%)  5/238 (2.10%) 
Pharyngitis * 1  5/236 (2.12%)  9/238 (3.78%) 
Tonsillitis * 1  4/236 (1.69%)  6/238 (2.52%) 
Rhinitis * 1  3/236 (1.27%)  9/238 (3.78%) 
Injury, poisoning and procedural complications     
Laceration * 1  2/236 (0.85%)  5/238 (2.10%) 
Joint injury * 1  0/236 (0.00%)  5/238 (2.10%) 
Investigations     
Blood creatine phosphokinase increased * 1  6/236 (2.54%)  3/238 (1.26%) 
Blood thyroid stimulating hormone increased * 1  1/236 (0.42%)  5/238 (2.10%) 
Metabolism and nutrition disorders     
Hypercholesterolemia * 1  0/236 (0.00%)  5/238 (2.10%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  11/236 (4.66%)  6/238 (2.52%) 
Arthralgia * 1  5/236 (2.12%)  4/238 (1.68%) 
Pain in extremity * 1  3/236 (1.27%)  8/238 (3.36%) 
Nervous system disorders     
Headache * 1  17/236 (7.20%)  25/238 (10.50%) 
Migraine * 1  1/236 (0.42%)  5/238 (2.10%) 
Psychiatric disorders     
Psychiatric disorders * 1  10/236 (4.24%)  9/238 (3.78%) 
Renal and urinary disorders     
Renal and urinary disorders * 1  4/236 (1.69%)  7/238 (2.94%) 
Reproductive system and breast disorders     
Reproductive system and breast disorders * 1  6/236 (2.54%)  4/238 (1.68%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  5/236 (2.12%)  8/238 (3.36%) 
Oropharyngeal pain * 1  4/236 (1.69%)  7/238 (2.94%) 
Respiratory disorder * 1  4/236 (1.69%)  6/238 (2.52%) 
Skin and subcutaneous tissue disorders     
Rash * 1  7/236 (2.97%)  3/238 (1.26%) 
Vascular disorders     
Hypertension * 1  2/236 (0.85%)  5/238 (2.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Investigator shall submit any paper or presentation to the Sponsor for review and comments at least 60 days prior to submitting the same to a third party. Upon receiving any request from the Sponsor to delete any Confidential Information or request to delay in publication up to 90 days to allow the filing of any Sponsor application, the Investigator shall take the request action. Investigator shall not be restricted after 18 months from completion of their site's performance in the study.
Results Point of Contact
Name/Title: Dr. Jeanne Novak
Organization: CBR International
Phone: 7207461190
Publications:
Responsible Party: Andromeda Biotech Ltd.
ClinicalTrials.gov Identifier: NCT01103284     History of Changes
Other Study ID Numbers: DiaPep277-1001
First Submitted: April 13, 2010
First Posted: April 14, 2010
Results First Submitted: November 16, 2015
Results First Posted: May 26, 2016
Last Update Posted: May 26, 2016