Clinical Trial Results:
A phase IIa study to characterize the effects of CCL2 inhibition with the Spiegelmer® NOX-E36 in patients with type 2 diabetes mellitus and albuminuria.
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Summary
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EudraCT number |
2011-005710-11 |
Trial protocol |
DE HU PL CZ |
Global end of trial date |
03 Dec 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Feb 2016
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First version publication date |
28 Jun 2015
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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 |
SNOXE36C301
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT01547897 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
study number: SNOXE36C301 | ||
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Sponsors
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Sponsor organisation name |
NOXXON Pharma AG
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Sponsor organisation address |
Max-Dohrn Strasse 8-10, Berlin, Germany, 10589
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Public contact |
Clinical Trial Disclosure Desk NOXXON, NOXXON Pharma AG, clinicaltrialdisclosuredesk@noxxon.com
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Scientific contact |
Clinical Trial Disclosure Desk NOXXON, NOXXON Pharma AG, clinicaltrialdisclosuredesk@noxxon.com
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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 Jun 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Dec 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Dec 2013
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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 characterize the effects of 12 weeks treatment with study drug on albumin-creatinine ratio (ACR) in patients with type 2 diabetes and albuminuria
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Protection of trial subjects |
This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, 2005/28/EC, and 2003/63/EC and relevant national and local legislations, and with the ethical principles that have their origin in the Declaration of Helsinki. Only subjects that met all the study inclusion and none of the exclusion criteria were randomized. Study drug administrations were performed by qualified and trained study personnel. Patient who received treatment were closely followed by means of adverse event reporting and vital signs. In the event of a study related adverse event, patient would have been monitored to determine the outcome. The clinical course of the AE will be followed up according to accepted standards of medical practice, even after the end of the period of observation, until a satisfactory explanation is found or the Investigator considers it medically justifiable to terminate follow-up.
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Background therapy |
Stable (unchanged medication for at least 3 months) treatment to control hypertension, hyperglycemia and (if applicable) dyslipidemia; Stable treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin II receptor blockers (ARBs) (renin-angiotensin system [RAS] blockade | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Mar 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Poland: 8
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Country: Number of subjects enrolled |
Czech Republic: 18
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Country: Number of subjects enrolled |
Germany: 28
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Country: Number of subjects enrolled |
Hungary: 21
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Country: Number of subjects enrolled |
Romania: 1
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Worldwide total number of subjects |
76
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EEA total number of subjects |
76
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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) |
53
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From 65 to 84 years |
23
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
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Pre-assignment
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Screening details |
215 patients were screened, 139 screen failed, after a screening period of up to 30 days duration, to ensure that the patient is stable on his/her concomitant therapy and life style 76 were randomized. | |||||||||||||||||||||
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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, Assessor, Carer | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Emapticap | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Emapticap Pegol
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Investigational medicinal product code |
NOX-E36
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mg/kg body weight two times per week over the 12 weeks treatment period;
a single-use, preservative-free, sterile solution of emapticap in an aqueous phosphate buffer pH 7 with EDTA and glucose for adjustment of tonicity to physiological levels
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
Placebo
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.5 mg/kg body weight two times per week over the 12 weeks treatment period;
a single-use, preservative-free, sterile solution of glucose, controlled to have physiological pH
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Baseline characteristics reporting groups
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Reporting group title |
Emapticap
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Emapticap
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- | ||
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End point title |
Change from baseline in ACR at the end of 12 weeks treatment | ||||||||||||
End point description |
The primary efficacy parameter is the effect of study drug on the change in ACR (Day 85 minus baseline) and was compared to placebo by ANCOVA using the additional factor gender and the covariates age, baseline ACR, and baseline hsCRP.
ANCOVA was performed based on the log-transformed data. The results were back-transformed to the original scale.
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End point type |
Primary
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End point timeframe |
Baseline and Day 85
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Statistical analysis title |
Emapticap vs Placebo | ||||||||||||
Comparison groups |
Emapticap v Placebo
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Number of subjects included in analysis |
75
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.221 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
geometric least square means ratio | ||||||||||||
Point estimate |
0.846
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.645 | ||||||||||||
upper limit |
1.108 | ||||||||||||
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End point title |
Change from baseline in HbA1c at the end of 12 weeks treatment | ||||||||||||
End point description |
Change in HbA1c (Day 85 minus baseline) compared to placebo by ANCOVA using the additional factor gender and the covariates age and baseline HbA1c.
ANCOVA was performed based on the log-transformed data. The results were back-transformed to the original scale.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 85
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Statistical analysis title |
Emapticap vs Placebo | ||||||||||||
Comparison groups |
Emapticap v Placebo
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Number of subjects included in analysis |
75
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.146 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
geometric least square means ratio | ||||||||||||
Point estimate |
0.964
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.918 | ||||||||||||
upper limit |
1.013 | ||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
baseline (Day 1) until end of follow up (Day 169)
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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 |
Emapticap
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2.5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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19 Mar 2012 |
Amendment 1:
“Glycemic disorders” was added to the secondary objective: “To evaluate the effect of study drug on markers of glycemic disorders, systemic inflammation, renal and liver disease, and cardiovascular function”;
Inclusion criterion 4 was more specified by adding “first”: 4) ACR > 100 mg/g calculated 3 times in first morning void urine;
The recommendations from EMA dated 22Dec2011 regarding the treatment of diabetic patients with aliskiren in combination with ACE inhibitors or ARBs are taken into account and inclusion criterion 7 was changed to “Stable treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or Angiotensin II receptor blockers (ARBs) (renin-angiotensin system [RAS] blockade)” and exclusion criterion 11 to “Use of thiazolidinedione class drugs, immune suppressants, steroid therapy (except for topical use or inhalation), chronic use of non-steroidal anti-inflammatory drug (NSAIDs), cyclooxygenase type 2 inhibitors (COX-2), two or more diuretic drugs and/or aliskiren”;
To reduce the burden for the patients, the oral glucose tolerance test (oGTT) was exchanged by the Homeostasis Model of Insulin Resistance (HOMA–IR, additional measurement of fasting glucose and fasting insulin).
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25 Sep 2012 |
Amendment 2:
The responsible Medical Monitor had changed;
Exclusion criterion 13, it was specified that with previous participation in the study randomization was meant;
A wrong transcription in formula for the eGFR was corrected;
eGFR was included in the interim analysis.
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21 Dec 2012 |
Amendment 3:
Clarification regarding the order of assessments during the screening period;
Inclusion criterion 3 was changed to “HbA1c between 6.0% and 10.5%, inclusive” to take recommendation of ADA (Jan 2012) into account;
Inclusion criterion 5 “high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L” was omitted because of the weak relationship between systemic (serum hsCRP) and local (kidney) inflammation. hsCRP remained as secondary endpoint. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| None reported | |||
