Clinical Trial Results:
A double-blind, randomised, placebo-controlled, crossover, allergen challenge study, evaluating the safety, tolerability and effects of intranasal administration of recombinant human Clara Cell 10 kDa (rhCC10) protein in subjects with allergic rhinitis.
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Summary
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EudraCT number |
2006-005420-17 |
Trial protocol |
SE |
Global end of trial date |
02 May 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Mar 2017
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First version publication date |
01 Mar 2017
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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 |
CC10-200601
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Therabron Therapeutics, Inc.
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Sponsor organisation address |
9430 Key West Ave. Suite 150, Rockville, United States, MD 20850
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Public contact |
Anita Fauchier, VP Regulatory Affairs & Quality Assurance, Therabron Therapeutics, Inc., anita.fauchier@therabron.com
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Scientific contact |
Alan Cohen, Senior Vice President & Chief Medical Officer, Therabron Therapeutics, Inc.
, alan.cohen@therabron.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 |
25 Sep 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 May 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
02 May 2007
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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 |
The study is a proof-of-concept study with the objective to investigate whether intranasal administration of rhCC10 can affect symptoms from nasal allergen challenge.
Primary:
To evaluate the effect of repeated doses of intranasal rhCC10 administration on nasal symptoms in subjects with allergic rhinitis. In addition, the onset of action of the study drug will be evaluated.
Secondary:
To evaluate the safety and tolerability of repeated doses of intranasal rhCC10 in subjects with allergic rhinitis.
To characterise the effects of rhCC10 treatment on individual nasal symptom scores, peak nasal inspiratory flow (PNIF), and laboratory analyses of nasal lavage fluid.
To evaluate the effects of rhCC10 after histamine challenge.
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Protection of trial subjects |
The study received prior CTA from the MPA, Sweden and IERC approval from the local ERC in Lund, Sweden.
Subjects were recruited who were capable of understanding and signing an Informed Consent Form.
The subjects were informed about the study, the treatments and methodologies used, and they were informed about their right to withdraw from the study at any time.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Jan 2007
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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 |
Sweden: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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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) |
39
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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 |
A total of 39 subjects (35 completed) were screened and randomised to rhCC10 or placebo for a 7-day treatment period followed by cross-over 7 day treatment period, with a wash-out period of 2 to 3 weeks in between treatment periods. The study was conducted at a single site in Sweden. | ||||||||||||||||||
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Pre-assignment
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Screening details |
At the screening visit a nasal allergen test was conducted for each subject. This was to enable an estimate of a symptom-producing, tolerable, and repeatable allergen dose for the nasal challenge series. A subject was randomised to treatment when laboratory results from this titration procedure were available. | ||||||||||||||||||
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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 |
Investigator, Subject | ||||||||||||||||||
Blinding implementation details |
To maintain the double blind design of the study, all study drugs were provided to the clinic in identical 10 mL glass vial reservoirs with Aptar 100 mcl nasal spray pumps. Labels were designed such that no information which would reveal the blind was included. Labels were numbered sequentially and a key was retained in the hospital pharmacy.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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rhCC10/placebo arm | ||||||||||||||||||
Arm description |
Each subject received treatment of 0.56 mg (100 μl) rhCC10 (intranasally into each nostril) daily for 7 days, followed by a wash-out period of 2 to 3 weeks, then 100 μl placebo (intranasally into each nostril) daily for 7 days. The daily dose was 1.1 mg rhCC10 or corresponding placebo (volume 200 μL). | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
recombinant human Clara Cell 10 kDa (rhCC10)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
rhCC10 5.6 mg/mL (±5%) solution in sterile, unbuffered normal saline (0.9 % NaCl). A dose of 0.56 mg rhCC10 was administered intranasally with a nasal spray into each nostril for 7 consecutive days. The daily dose was 1.1 mg rhCC10.
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Arm title
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Placebo/rhCC10 arm | ||||||||||||||||||
Arm description |
Each subject received treatment 100 μl placebo (intranasally into each nostril) daily for 7 days, followed by a wash-out period of 2 to 3 weeks, then 0.56 mg (100 μl) rhCC10 (intranasally into each nostril) daily for 7 days. The daily dose was 1.1 mg rhCC10 or corresponding placebo (volume 200 μL). | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
A dose of placebo volume 100 μL was administered intranasally with a nasal spray into each nostril for 7 consecutive days. The daily dose of placebo was volume 200 μL.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
This reporting group is all subject in the clinical trial and therefore consists of the 39 subjects randomised to both arms of the trial. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety analysis set includes all randomised patients who took study medication. The analysis of all safety and tolerability variables was performed using the safety analysis set.
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The full analysis set (FAS) for efficacy analysis is defined as all randomised subjects who received at least two doses of rhCC10, two doses of placebo and for whom at least one observation was recorded for the primary efficacy variable at each treatment period. The analysis of all efficacy variables was performed using the FAS.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The per protocol analysis set includes patients that had no major protocol violation and had at least two valid readings of primary outcome variables from the three last days of each allergen challenge period. Moreover the patients had to take at least 4 doses of medication at both treatment periods. The analysis of the primary efficacy variable was performed using the per protocol analysis.
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End points reporting groups
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Reporting group title |
rhCC10/placebo arm
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Reporting group description |
Each subject received treatment of 0.56 mg (100 μl) rhCC10 (intranasally into each nostril) daily for 7 days, followed by a wash-out period of 2 to 3 weeks, then 100 μl placebo (intranasally into each nostril) daily for 7 days. The daily dose was 1.1 mg rhCC10 or corresponding placebo (volume 200 μL). | ||
Reporting group title |
Placebo/rhCC10 arm
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Reporting group description |
Each subject received treatment 100 μl placebo (intranasally into each nostril) daily for 7 days, followed by a wash-out period of 2 to 3 weeks, then 0.56 mg (100 μl) rhCC10 (intranasally into each nostril) daily for 7 days. The daily dose was 1.1 mg rhCC10 or corresponding placebo (volume 200 μL). | ||
Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis set includes all randomised patients who took study medication. The analysis of all safety and tolerability variables was performed using the safety analysis set.
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The full analysis set (FAS) for efficacy analysis is defined as all randomised subjects who received at least two doses of rhCC10, two doses of placebo and for whom at least one observation was recorded for the primary efficacy variable at each treatment period. The analysis of all efficacy variables was performed using the FAS.
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per protocol analysis set includes patients that had no major protocol violation and had at least two valid readings of primary outcome variables from the three last days of each allergen challenge period. Moreover the patients had to take at least 4 doses of medication at both treatment periods. The analysis of the primary efficacy variable was performed using the per protocol analysis.
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End point title |
Means of total nasal symptom scores (TNSS) | |||||||||
End point description |
Means of total nasal symptom scores (TNSS) during the last 3 days of each challenge period of 7 days.
The TNSS was recorded 10 minutes after each allergen challenge and daily in the morning and in the evening; the difference in TNSS values between rhCC10 treatment and placebo treatment was calculated.
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End point type |
Primary
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End point timeframe |
During the last 3 days of each challenge period of 7 days.
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Statistical analysis title |
Primary objective - full analysis set | |||||||||
Statistical analysis description |
The primary objective of the study was to evaluate the effect of repeated doses of intranasal rhCC10 administration in subjects with allergic rhinitis.
The primary hypothesis was:
RhCC10 is superior to placebo in preventing total nasal symptom score (TNSS) recorded 10 minutes after allergen challenge during the last three days of each allergen challenge period.
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Comparison groups |
Full analysis set v Per protocol analysis set
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.1127 [1] | |||||||||
Method |
ANOVA | |||||||||
Parameter type |
Total nasal symptom score | |||||||||
Confidence interval |
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| Notes [1] - The difference between placebo and rhCC10 by means of total nasal symptom scores (TNSS) during the last 3 days of the challenge period of 7 days was in favour of placebo (p=0.0932, per protocol analysis set; p=0.1127, full analysis set). |
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Statistical analysis title |
Primary objective - per protocol analysis set | |||||||||
Statistical analysis description |
The primary objective of the study was to evaluate the effect of repeated doses of intranasal rhCC10 administration in subjects with allergic rhinitis.
The primary hypothesis was:
RhCC10 is superior to placebo in preventing total nasal symptom score (TNSS) recorded 10 minutes after allergen challenge during the last three days of each allergen challenge period.
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Comparison groups |
Per protocol analysis set v Full analysis set
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0932 [2] | |||||||||
Method |
ANOVA | |||||||||
Parameter type |
Total nasal symptom score | |||||||||
Confidence interval |
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| Notes [2] - The difference between placebo and rhCC10 by means of total nasal symptom scores (TNSS) during the last 3 days of the challenge period of 7 days was in favour of placebo (p=0.0932, per protocol analysis set; p=0.1127, full analysis set). |
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End point title |
Type and incidence of adverse events (AEs) | ||||||||
End point description |
Type and incidence of adverse events (AEs).
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End point type |
Secondary
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End point timeframe |
Duration of trial.
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| No statistical analyses for this end point | |||||||||
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End point title |
To characterise the effects of rhCC10 treatment on individual nasal symptom scores, peak nasal inspiratory flow (PNIF), and laboratory analyses of nasal lavage fluid. | ||||||||||||
End point description |
Difference between rhCC10 treatment and placebo on individual nasal symptoms :
1. Nasal congestion
2. Rhinorrea
3. Sneezy/itchy nose
Difference between rhCC10 treatment and placebo on PNIF,
Difference in nasal lavage content of eosinophilic cationic protein (ECP), tryptase, and myeloperoxidase between rhCC10 treatment and placebo.
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End point type |
Secondary
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End point timeframe |
Duration of trial.
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Statistical analysis title |
1. Treatment of nasal congestion | ||||||||||||
Statistical analysis description |
Difference between rhCC10 treatment and placebo on individual nasal symptoms.
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Comparison groups |
rhCC10/placebo arm v Placebo/rhCC10 arm
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.886 [3] | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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| Notes [3] - Difference between placebo and rhCC10 treatment by mean of nasal congestion was in favour of placebo (p=0.8860). |
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Statistical analysis title |
2. Treatment of rhinorrea | ||||||||||||
Statistical analysis description |
Difference between rhCC10 treatment and placebo on individual nasal symptoms.
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Comparison groups |
rhCC10/placebo arm v Placebo/rhCC10 arm
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0493 [4] | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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| Notes [4] - Difference between placebo and rhCC10 treatment by mean of rhinorrea was statistically significantly better with placebo (p=0.0493) |
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Statistical analysis title |
3. Treatment of itchy nose | ||||||||||||
Statistical analysis description |
Difference between rhCC10 treatment and placebo on individual nasal symptoms.
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Comparison groups |
rhCC10/placebo arm v Placebo/rhCC10 arm
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1784 [5] | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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| Notes [5] - Difference between placebo and rhCC10 treatment by mean of sneezy/itchy was in favour of placebo (p= 0.1784). |
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Statistical analysis title |
Difference in rhCC10 and placebo on PNIF | ||||||||||||
Statistical analysis description |
To characterise the effects of rhCC10 treatment on individual nasal symptom scores, peak nasal inspiratory flow (PNIF), and laboratory analyses of nasal lavage fluid.
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Comparison groups |
rhCC10/placebo arm v Placebo/rhCC10 arm
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0363 [6] | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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| Notes [6] - Difference between placebo and rhCC10 treatment of peak nasal inspiratory flow (PNIF) was statistically significant better of rhCC10 (p=0.0363). |
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End point title |
Difference in α2-macroglobulin response between rhCC10 treatment and placebo after histamine challenge test. | ||||||||
End point description |
Difference in α2-macroglobulin response between rhCC10 treatment and placebo after histamine challenge test.
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End point type |
Secondary
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End point timeframe |
Duration of trial.
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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 |
The Adverse Event reporting period for began upon receiving the first dose of investigational medication and ended at the 2-week post discontinuation of investigational medication visit (follow-up visit).
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Adverse event reporting additional description |
During the study when there was a safety evaluation, the investigator or site staff was responsible for detecting, documenting and reporting AEs and SAEs.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.1
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Reporting groups
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Reporting group title |
rhCC10/placebo arm
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Reporting group description |
rhCC10/placebo arm | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/rhCC10 arm
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Reporting group description |
Placebo/rhCC10 arm | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
