Exploratory Study to Evaluate QR-010 in Subjects With Cystic Fibrosis ΔF508 CFTR Mutation
Study Details
Study Description
Brief Summary
Exploratory proof of concept study to determine whether intranasal administration of QR-010 in subjects with cystic fibrosis, homozygous or compound heterozygous for the ΔF508 mutation, can increase the function of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Detailed Description
This is an open-label, multi-center, exploratory study to estimate the effect of intranasal administration of QR-010 on the nasal mucosa in the restoration of CFTR function, as measured by nasal potential difference (NPD), in the nasal epithelium of adult subjects with CF who are homozygous or compound heterozygous for the ΔF508 CFTR mutation.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: ΔF508 Homozygous QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks. |
Drug: QR-010
Single-stranded RNA antisense oligonucleotide in isoosmolar solution
|
Experimental: ΔF508 Compound Heterozygous QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks. |
Drug: QR-010
Single-stranded RNA antisense oligonucleotide in isoosmolar solution
|
Outcome Measures
Primary Outcome Measures
- Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD). [Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.]
The primary endpoint was the within-subject change from baseline in total chloride transport as measured by NPD, after the Chloride-free+isoproterenol solution (Cl-free+iso), and was based on the average measurements of both nostrils. To provide baseline stability, baseline was defined as the average of the two most recent pre-dose values, where each pre-dose value was the average of two nostrils. A negative change from baseline of Cl-free+iso shows an improvement.
Secondary Outcome Measures
- Number of Subjects With a -6.6 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study. [2 and 4 weeks, and at 3 weeks post-treatment.]
This analysis is the proportion (amount) of subjects with an average Cl-free+iso actual value of -6.6 mV or more negative after treatment (ie, responders), as measured by NPD and was based on the average measurements of both nostrils. The actual value of -6.6 mV is used to discriminate individuals with CF (>-6.6 mV) from normal individuals (≤ -6.6 mV).
- Number of Subjects With a -4 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study. [2 and 4 weeks, and at 3 weeks post-treatment.]
This analysis is the proportion of subjects with an average Cl-free+iso actual value of -4 mV or more negative after treatment (ie, responders), as measured by NPD and was based on the average measurements of both nostrils. The value of -4 mV is considered a clinically relevant response to treatment based on data from studies of other CFTR therapies.
- Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study. [Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.]
This endpoint was the within-subject change in Sodium transport (average Potential Difference prior to perfusion of any solution); this is the average of Potential Difference measured at five sites in the inferior meatus of the nose. A positive change from baseline shows an improvement.
- The Mean Change in CFTR-mediated Total Chloride Transport. [2 and 4 weeks, and at 3 weeks post-treatment.]
The mean change in CFTR-mediated Total Chloride Transport compared to Baseline, per cohort; this is the mean of Potential Difference measured at five sites in the inferior meatus of the nose measured in millivolts (mV). A negative change from baseline shows an improvement.
- Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study. [3 weeks post-treatment.]
Number of subjects experiencing serious adverse events from baseline through End of Study.
- Number of Subject Discontinuations Due to AEs From Baseline Through End of Study. [3 weeks post-treatment.]
Number of subject discontinuations due to AEs from baseline through End of Study. No discontinuations occurred.
- Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study. [3 weeks post-treatment.]
Number of subjects experiencing at least one abnormality in laboratory parameters (chemistry, hematology and urinalysis) that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study.
- Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study. [3 weeks post-treatment.]
Number of subjects experiencing at least one abnormality vital signs & oximetry that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study.
- Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study. [3 weeks post-treatment.]
Number of subjects experiencing at least one abnormality in physical examination that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study.
- Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study. [3 weeks post-treatment.]
The NERS was performed by site staff prior to each dose and as part of the NPD procedure; it is a set of scales ranging from 0 (no symptoms) to 3 (most severe symptoms) for assessing the severity of each of the following nasal symptoms, separately for each nostril: mucosal disruption, edema, erythema, polyp, secretions. The range of the total sum is 0-30.
- Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study. [3 weeks post-treatment.]
Subjects were asked to score a list of 22 symptoms on the SNOT-22 regarding social and emotional consequences. Outcomes were graded as 0 (no problem), to 5 (problem as bad as it could be). The list included: need to blow nose, sneezing, dripping nose, cough, postnasal drip, dense nasal drip, ear fullness, dizziness, ear pain, facial pain/pressure, difficulty falling asleep, waking at night, lack of a good night's sleep, waking up tired, fatigue, reduced productivity, reduced concentration, frustrated/restless/irritable, sad, embarrassed, decrease in smell and taste, and nasal obstruction. The range of the total sum is 0-110, with higher values indicating worse outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of > 60 mmol/L
-
Nasal potential difference (NPD) measurement at Screening consistent with CF
-
Confirmation of CFTR gene mutations homozygous or compound heterozygous for the ΔF508 mutation
-
Body mass index (BMI) of ≥ 18 kg/m2
-
Non-smoking for a minimum of 2 years
-
Stable lung function
-
FEV1 ≥40% of predicted normal for age, gender, and height at Screening
Exclusion Criteria:
-
Breast-feeding or pregnant
-
Acute allergy or infection affecting nasal conditions not resolved within 14 days prior Screening
-
Use of lumacaftor or ivacaftor
-
Use of any investigational drug or device
-
Hemoptysis
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
2 | National Jewish Health | Denver | Colorado | United States | 80206 |
3 | Cincinnati Childrens Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
4 | U.Z. Leuven | Leuven | Belgium | 3000 | |
5 | Hopital Necker-Enfants Malades | Paris | France | 75743 |
Sponsors and Collaborators
- ProQR Therapeutics
- European Commission
Investigators
- Principal Investigator: John P Clancy, MD, Cincinnati Childrens Hospital Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PQ-010-002
Study Results
Participant Flow
Recruitment Details | Subjects were screened and enrolled at 5 hospitals in the USA and Europe. Screenings for Cohort 1 and Cohort 2 occurred in parallel between between 19th October 2015 and 14th July 2016. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR (Cystic Fibrosis Transmembrane conductance Regulator) mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Period Title: Overall Study | ||
STARTED | 10 | 8 |
COMPLETED | 10 | 8 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation | Total |
---|---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Total of all reporting groups |
Overall Participants | 10 | 8 | 18 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
10
100%
|
8
100%
|
18
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Full Range) ] | |||
Mean (Full Range) [years] |
25.80
|
36.00
|
30.33
|
Sex: Female, Male (Count of Participants) | |||
Female |
4
40%
|
4
50%
|
8
44.4%
|
Male |
6
60%
|
4
50%
|
10
55.6%
|
Region of Enrollment (Count of Participants) | |||
Belgium |
2
20%
|
2
25%
|
4
22.2%
|
United States |
4
40%
|
5
62.5%
|
9
50%
|
France |
4
40%
|
1
12.5%
|
5
27.8%
|
FEV1% predicted (Percent of the predicted value) [Mean (Full Range) ] | |||
Mean (Full Range) [Percent of the predicted value] |
74.22
|
73.55
|
73.92
|
Outcome Measures
Title | Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD). |
---|---|
Description | The primary endpoint was the within-subject change from baseline in total chloride transport as measured by NPD, after the Chloride-free+isoproterenol solution (Cl-free+iso), and was based on the average measurements of both nostrils. To provide baseline stability, baseline was defined as the average of the two most recent pre-dose values, where each pre-dose value was the average of two nostrils. A negative change from baseline of Cl-free+iso shows an improvement. |
Time Frame | Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set: 3 subjects from Cohort 1 and 1 subject from Cohort 2 didn't meet the NPD entry criterion and were excluded from the per protocol analysis. Further 1 subject from Cohort 1 did not have an interpretable Week 4 NPD measurement. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 7 | 7 |
Baseline |
1.86
(3.360)
|
-0.75
(3.868)
|
Week 2 |
-1.11
(8.062)
|
1.66
(3.937)
|
Week 4 |
-1.92
(4.837)
|
1.43
(2.644)
|
3 weeks post-treatment |
-1.86
(6.736)
|
2.27
(6.546)
|
Title | Number of Subjects With a -6.6 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study. |
---|---|
Description | This analysis is the proportion (amount) of subjects with an average Cl-free+iso actual value of -6.6 mV or more negative after treatment (ie, responders), as measured by NPD and was based on the average measurements of both nostrils. The actual value of -6.6 mV is used to discriminate individuals with CF (>-6.6 mV) from normal individuals (≤ -6.6 mV). |
Time Frame | 2 and 4 weeks, and at 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set: 3 subjects from Cohort 1 and 1 subject from Cohort 2 didn't meet the NPD entry criterion and were excluded from the per protocol analysis. Further 1 subject from Cohort 1 did not have an interpretable Week 4 NPD measurement. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 7 | 7 |
Week 2 |
1
10%
|
0
0%
|
Week 4 |
1
10%
|
0
0%
|
3 weeks post-treatment |
2
20%
|
0
0%
|
Title | Number of Subjects With a -4 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study. |
---|---|
Description | This analysis is the proportion of subjects with an average Cl-free+iso actual value of -4 mV or more negative after treatment (ie, responders), as measured by NPD and was based on the average measurements of both nostrils. The value of -4 mV is considered a clinically relevant response to treatment based on data from studies of other CFTR therapies. |
Time Frame | 2 and 4 weeks, and at 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set: 3 subjects from Cohort 1 and 1 subject from Cohort 2 didn't meet the NPD entry criterion and were excluded from the per protocol analysis. Further 1 subject from Cohort 1 did not have an interpretable Week 4 NPD measurement. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 7 | 7 |
Week 2 |
3
30%
|
1
12.5%
|
Week 4 |
2
20%
|
1
12.5%
|
3 weeks post-treatment |
4
40%
|
0
0%
|
Title | Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study. |
---|---|
Description | This endpoint was the within-subject change in Sodium transport (average Potential Difference prior to perfusion of any solution); this is the average of Potential Difference measured at five sites in the inferior meatus of the nose. A positive change from baseline shows an improvement. |
Time Frame | Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set: 3 subjects from Cohort 1 and 1 subject from Cohort 2 didn't meet the NPD entry criterion and were excluded from the per protocol analysis. Further 1 subject from Cohort 1 did not have an interpretable Week 4 NPD measurement. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 7 | 7 |
Baseline |
-31.92
(8.777)
|
-27.02
(11.412)
|
Week 2 |
-33.80
(9.922)
|
-27.48
(9.230)
|
Week 4 |
-25.14
(10.809)
|
-25.52
(10.445)
|
3 weeks post-treatment |
-31.56
(7.791)
|
-27.59
(6.291)
|
Title | The Mean Change in CFTR-mediated Total Chloride Transport. |
---|---|
Description | The mean change in CFTR-mediated Total Chloride Transport compared to Baseline, per cohort; this is the mean of Potential Difference measured at five sites in the inferior meatus of the nose measured in millivolts (mV). A negative change from baseline shows an improvement. |
Time Frame | 2 and 4 weeks, and at 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Per Protocol Set: 3 subjects from Cohort 1 and 1 subject from Cohort 2 didn't meet the NPD entry criterion and were excluded from the per protocol analysis. Further 1 subject from Cohort 1 did not have an interpretable Week 4 NPD measurement. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 7 | 7 |
Week 2 |
-2.44
(2.00)
|
1.88
(2.00)
|
Week 4 |
-3.46
(1.88)
|
1.65
(1.70)
|
3 weeks post-treatment |
-3.19
(2.26)
|
2.49
(2.26)
|
Title | Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study. |
---|---|
Description | Number of subjects experiencing serious adverse events from baseline through End of Study. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Title | Number of Subject Discontinuations Due to AEs From Baseline Through End of Study. |
---|---|
Description | Number of subject discontinuations due to AEs from baseline through End of Study. No discontinuations occurred. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study; incidence of discontinuations due to AEs from baseline through End of Study will be reported in the Adverse Events section. No discontinuations occurred. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Title | Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study. |
---|---|
Description | Number of subjects experiencing at least one abnormality in laboratory parameters (chemistry, hematology and urinalysis) that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Title | Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study. |
---|---|
Description | Number of subjects experiencing at least one abnormality vital signs & oximetry that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Count of Participants [Participants] |
0
0%
|
0
0%
|
Title | Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study. |
---|---|
Description | Number of subjects experiencing at least one abnormality in physical examination that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Count of Participants [Participants] |
3
30%
|
4
50%
|
Title | Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study. |
---|---|
Description | The NERS was performed by site staff prior to each dose and as part of the NPD procedure; it is a set of scales ranging from 0 (no symptoms) to 3 (most severe symptoms) for assessing the severity of each of the following nasal symptoms, separately for each nostril: mucosal disruption, edema, erythema, polyp, secretions. The range of the total sum is 0-30. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. 1 measurement was missing from 1 subject in Cohort 2 for Week 4. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Baseline |
12.20
(1.317)
|
11.50
(1.773)
|
Day 3 |
11.60
(1.647)
|
13.38
(3.335)
|
Day 5 |
11.50
(1.650)
|
12.25
(2.550)
|
Week 1 |
12.60
(2.171)
|
12.00
(1.852)
|
Day 10 |
11.50
(1.900)
|
11.88
(2.532)
|
Day 12 |
11.50
(1.269)
|
11.50
(1.414)
|
Week 2 |
12.50
(2.635)
|
11.75
(1.909)
|
Day 17 |
11.20
(2.098)
|
12.00
(2.878)
|
Day 19 |
11.90
(2.183)
|
11.63
(1.923)
|
Week 3 |
13.10
(2.685)
|
12.63
(2.134)
|
Day 24 |
11.90
(2.378)
|
12.38
(2.326)
|
Week 4 |
13.00
(2.828)
|
11.71
(1.890)
|
3 weeks post-treatment |
12.30
(2.541)
|
12.75
(3.327)
|
Title | Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study. |
---|---|
Description | Subjects were asked to score a list of 22 symptoms on the SNOT-22 regarding social and emotional consequences. Outcomes were graded as 0 (no problem), to 5 (problem as bad as it could be). The list included: need to blow nose, sneezing, dripping nose, cough, postnasal drip, dense nasal drip, ear fullness, dizziness, ear pain, facial pain/pressure, difficulty falling asleep, waking at night, lack of a good night's sleep, waking up tired, fatigue, reduced productivity, reduced concentration, frustrated/restless/irritable, sad, embarrassed, decrease in smell and taste, and nasal obstruction. The range of the total sum is 0-110, with higher values indicating worse outcome. |
Time Frame | 3 weeks post-treatment. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population: all subjects enrolled in the study. |
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation |
---|---|---|
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. |
Measure Participants | 10 | 8 |
Baseline |
14.90
(5.896)
|
19.13
(17.707)
|
Week 2 |
13.60
(8.369)
|
15.38
(18.601)
|
Week 4 |
14.50
(11.048)
|
14.13
(16.084)
|
3 weeks post-treatment |
10.70
(8.301)
|
14.50
(10.915)
|
Adverse Events
Time Frame | After the subject had provided informed consent, but prior to initiation of IMP, only SAEs caused by a protocol-mandated intervention were collected. After initiation of IMP, all AEs and SAEs, regardless of attribution, were collected until at least 30 days following the last administration of IMP or initiation of new therapy, whichever was earlier. | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation | ||
Arm/Group Description | Subjects homozygous for the F508del-CFTR mutation were enrolled into Cohort 1 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | Subjects compound heterozygous for the F508del-CFTR mutation were enrolled into Cohort 2 and received QR-010 10 mg (5 mg/250 μL saline per nostril) via bilateral intranasal administration three times a week for 4 weeks for a total of 12 doses. | ||
All Cause Mortality |
||||
Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/10 (0%) | 0/8 (0%) | ||
Serious Adverse Events |
||||
Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/10 (0%) | 0/8 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Cohort 1: Homozygous for the F508del-CFTR Mutation | Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/10 (90%) | 7/8 (87.5%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 0/10 (0%) | 1/8 (12.5%) | ||
Constipation | 1/10 (10%) | 0/8 (0%) | ||
Gastritis | 1/10 (10%) | 0/8 (0%) | ||
Gastrooesophageal reflux disease | 0/10 (0%) | 1/8 (12.5%) | ||
Glossitis | 0/10 (0%) | 1/8 (12.5%) | ||
Nausea | 2/10 (20%) | 1/8 (12.5%) | ||
Vomiting | 1/10 (10%) | 0/8 (0%) | ||
General disorders | ||||
Fatigue | 0/10 (0%) | 4/8 (50%) | ||
Malaise | 0/10 (0%) | 1/8 (12.5%) | ||
Pyrexia | 1/10 (10%) | 3/8 (37.5%) | ||
Hepatobiliary disorders | ||||
Galbladder pain | 0/10 (0%) | 1/8 (12.5%) | ||
Infections and infestations | ||||
Infective pulmonary exacerbation of cystic fibrosis | 1/10 (10%) | 0/8 (0%) | ||
Nasopharyngitis | 1/10 (10%) | 0/8 (0%) | ||
Rhinitis | 3/10 (30%) | 0/8 (0%) | ||
Staphylococcal infection | 1/10 (10%) | 0/8 (0%) | ||
Upper respiratory tract infection | 1/10 (10%) | 0/8 (0%) | ||
Injury, poisoning and procedural complications | ||||
Ligament sprain | 0/10 (0%) | 1/8 (12.5%) | ||
Wound | 0/10 (0%) | 1/8 (12.5%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 0/10 (0%) | 1/8 (12.5%) | ||
Dehydration | 0/10 (0%) | 1/8 (12.5%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 0/10 (0%) | 1/8 (12.5%) | ||
Back pain | 0/10 (0%) | 1/8 (12.5%) | ||
Myalgia | 1/10 (10%) | 0/8 (0%) | ||
Nervous system disorders | ||||
Headache | 0/10 (0%) | 2/8 (25%) | ||
Migraine | 0/10 (0%) | 1/8 (12.5%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Bronchospasm | 1/10 (10%) | 0/8 (0%) | ||
Cough | 2/10 (20%) | 3/8 (37.5%) | ||
Epistaxis | 1/10 (10%) | 1/8 (12.5%) | ||
Increased viscosity of bronchial secretion | 1/10 (10%) | 0/8 (0%) | ||
Intranasal hypoaesthesia | 1/10 (10%) | 0/8 (0%) | ||
Nasal congestion | 1/10 (10%) | 1/8 (12.5%) | ||
Nasal mucosal erosion | 1/10 (10%) | 0/8 (0%) | ||
Paranasal sinus discomfort | 0/10 (0%) | 1/8 (12.5%) | ||
Paranasal sinus hypersecretion | 0/10 (0%) | 1/8 (12.5%) | ||
Respiratory tract congestion | 2/10 (20%) | 0/8 (0%) | ||
Rhinorrhoea | 3/10 (30%) | 0/8 (0%) | ||
Sinus congestion | 0/10 (0%) | 2/8 (25%) | ||
Sneezing | 0/10 (0%) | 1/8 (12.5%) | ||
Sputum increased | 1/10 (10%) | 1/8 (12.5%) | ||
Skin and subcutaneous tissue disorders | ||||
Dermatitis | 1/10 (10%) | 0/8 (0%) | ||
Pruritus | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigators are restricted from disclosure or results until after multi-center publication or 12 months after the completion of the Study at all participating research centers. Sponsor can review results communication prior to public release and can embargo communications regarding trial results for a period that is more than 60 days (varying per site). Sponsor may request redaction of confidential information.
Results Point of Contact
Name/Title | Medical Monitor |
---|---|
Organization | ProQR Therapeutics |
Phone | +31 6 20 183 437 |
clinical@proqr.com |
- PQ-010-002