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Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients

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: NCT02532764
Recruitment Status : Completed
First Posted : August 26, 2015
Results First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
ProQR Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: QR-010
Drug: Placebo
Enrollment 70
Recruitment Details The enrollment of this clinical trial followed a staggered approach; a new SAD cohort was enrolled following review of the previous SAD cohort. The first MAD cohort opened following the review of the first two SAD cohorts. Subsequent MAD dosing cohorts were initiated following review of the corresponding supportive SAD and MAD cohorts.
Pre-assignment Details  
Arm/Group Title QR-010 SAD 6.25mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description QR-010 administered via inhalation as a single dose. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation QR-010 administered via inhalation as a single dose. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation QR-010 administered via inhalation as a single dose. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation QR-010 administered via inhalation as a single dose. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation Placebo (normal saline) administered via inhalation as a single dose Placebo: Normal Saline QR-010 administered via inhalation three times weekly for four weeks. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation. QR-010 administered via inhalation three times weekly for four weeks. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation. QR-010 administered via inhalation three times weekly for four weeks. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation. QR-010 administered via inhalation three times weekly for four weeks. QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalation.

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Period Title: Single Ascending Dose (SAD) Cohorts
Started 6 6 9 6 9 0 0 0 0 0
Completed 6 6 9 6 9 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Multiple Ascending Dose (MAD) Cohorst
Started 0 0 0 0 0 6 6 7 6 9
Completed 0 0 0 0 0 6 6 6 5 8
Not Completed 0 0 0 0 0 0 0 1 1 1
Reason Not Completed
Met stopping criteria             0             0             0             0             0             0             0             1             1             1
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD Total
Hide Arm/Group Description

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Total of all reporting groups
Overall Number of Baseline Participants 6 6 9 6 9 6 6 7 6 9 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
6
 100.0%
9
 100.0%
6
 100.0%
9
 100.0%
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
9
 100.0%
70
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
25.8  (8.01) 21.5  (2.95) 27.2  (7.31) 22.7  (3.88) 24.8  (8.26) 22.7  (2.66) 27.7  (10.42) 32.3  (10.63) 23.3  (4.18) 26.3  (6.69) 25.6  (7.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
Female
4
  66.7%
5
  83.3%
5
  55.6%
2
  33.3%
3
  33.3%
3
  50.0%
3
  50.0%
5
  71.4%
2
  33.3%
6
  66.7%
38
  54.3%
Male
2
  33.3%
1
  16.7%
4
  44.4%
4
  66.7%
6
  66.7%
3
  50.0%
3
  50.0%
2
  28.6%
4
  66.7%
3
  33.3%
32
  45.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
6
 100.0%
9
 100.0%
6
 100.0%
9
 100.0%
6
 100.0%
6
 100.0%
7
 100.0%
6
 100.0%
9
 100.0%
70
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
Canada 0 0 2 0 0 0 0 1 0 0 3
Belgium 1 1 0 0 2 1 1 0 1 2 9
United States 1 1 4 5 1 1 1 0 1 3 18
Czechia 2 2 0 0 2 0 2 0 1 0 9
Denmark 0 0 1 0 2 1 0 2 1 1 8
Italy 1 1 0 0 2 1 1 1 0 0 7
United Kingdom 1 0 1 1 0 1 0 0 1 3 8
France 0 0 1 0 0 0 0 1 0 0 2
Germany 0 1 0 0 0 1 1 2 1 0 6
Weight (kg)  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
59.4  (9.28) 64.8  (2.26) 67.5  (13.00) 57.7  (9.70) 62.2  (6.48) 66.8  (6.87) 62.6  (8.97) 67.1  (4.35) 61.3  (13.37) 59.6  (9.19) 63.0  (9.11)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
22.1  (2.54) 24.1  (2.33) 23.0  (2.59) 21.5  (2.91) 21.4  (1.73) 23.5  (2.76) 22.8  (2.65) 23.6  (1.56) 21.3  (2.86) 20.9  (1.56) 22.3  (2.42)
FEV1   [1] 
Mean (Standard Deviation)
Unit of measure:  L
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
3.24  (0.877) 3.15  (0.666) 3.78  (1.092) 3.06  (0.700) 3.64  (0.748) 3.49  (0.590) 3.19  (0.600) 2.85  (0.577) 3.40  (0.993) 3.18  (0.778) 3.32  (0.792)
[1]
Measure Description: Lung function; forced expiratory volume in 1 second
ppFEV1   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 6 participants 6 participants 9 participants 6 participants 9 participants 6 participants 6 participants 7 participants 6 participants 9 participants 70 participants
92.3  (13.31) 91.4  (19.93) 97.3  (20.39) 80.9  (8.99) 91.8  (12.91) 90.7  (14.28) 89.0  (14.21) 79.9  (10.14) 84.7  (13.59) 86.7  (11.91) 88.8  (14.54)
[1]
Measure Description: Lung function; percent predicted Forced Expiratory Volume in 1 second
1.Primary Outcome
Title Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study
Hide Description Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received either QR-010 or placebo
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 9 6 9 6 6 7 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
3
  50.0%
2
  33.3%
7
  77.8%
4
  66.7%
2
  22.2%
5
  83.3%
5
  83.3%
6
  85.7%
5
  83.3%
9
 100.0%
2.Primary Outcome
Title Severity of Treatment Emergent Adverse Events From Baseline Through End of Study
Hide Description

Assessment of severity of treatment emergent adverse events (TEAEs).

Severity is graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Modified for CF (CTCAE v4.03). For events not present in this listing the following grading was applied:

Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Moderate: Minimal, local, or noninvasive intervention indicated; discomfort sufficient to reduce or interfere with daily activities; Severe: Medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization may be indicated; disabling; limits self-care with significant interference with daily activities; incapacitating with inability to perform self care activities of daily living; Life-threatening: Urgent intervention indicated; immediate risk of death.

Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received either QR-010 or placebo.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 9 6 9 6 6 7 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
Mild
3
  50.0%
2
  33.3%
5
  55.6%
4
  66.7%
2
  22.2%
5
  83.3%
4
  66.7%
5
  71.4%
1
  16.7%
5
  55.6%
Moderate
0
   0.0%
0
   0.0%
2
  22.2%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
4
  66.7%
3
  33.3%
Severe
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  11.1%
Life-Threatening
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Death
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit.
Hide Description DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received either QR-010 or placebo. There were no Dose Limiting Toxicities (DLTs) reported in the SAD or MAD cohorts.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 9 6 9 6 6 7 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Secondary Outcome
Title Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings.
Hide Description Number of subjects experiencing at least one abnormality for the categories laboratory parameters, vital signs, ECG, spirometry and physical findings that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely.
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received either QR-010 or placebo.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 9 6 9 6 6 7 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
laboratory parameters
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
3
  33.3%
vital signs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
ECG
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Spirometry
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  33.3%
1
  11.1%
physical findings
2
  33.3%
2
  33.3%
2
  22.2%
3
  50.0%
0
   0.0%
3
  50.0%
4
  66.7%
1
  14.3%
1
  16.7%
4
  44.4%
5.Secondary Outcome
Title Maximum Serum Concentration
Hide Description Cmax: QR-010 maximum serum concentrations
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
Study population included all subjects treated either with QR-010 or placebo. Quantifiable serum concentrations are only available for the 50mg SAD and 50 mg MAD cohorts.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 4 0 0 0 0 6 0
Mean (Standard Deviation)
Unit of Measure: ng/mL
Dose 1 2.9  (1.2) 4.53  (3.38)
Week 4, Dose 12 NA [1]   (NA) 3.63  (2.73)
[1]
for SAD cohorts, there is no Week 4, Dose 12 timepoint
6.Secondary Outcome
Title Time to Maximum Serum Concentration
Hide Description Tmax: Time to Cmax of QR-010 serum concentrations.
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
Population included all subjects treated with either QR-010 or placebo. Quantifiable serum concentrations are only available for the 50mg SAD and MAD cohorts.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 4 0 0 0 0 6 0
Median (Full Range)
Unit of Measure: hour
Dose 1
0.6
(0.5 to 2.1)
0.5
(0.5 to 3.0)
Week 4, Dose 12
NA [1] 
(NA to NA)
1.0
(1.0 to 2.0)
[1]
for SAD cohorts, there is no Week 4, Dose 12 timepoint
7.Secondary Outcome
Title Terminal Half-life (T1/2)
Hide Description The terminal elimination half-life will be estimated by non-linear regression analysis of the terminal elimination slope
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The terminal half-life is not reported because the %AUC (Area Under the Curve) extrapolation was too large.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Area Under the Curve to Final Sample [AUC(0-last)]
Hide Description Area under the curve to the final sample with a concentration greater than lower limit of quantification (LLQ) will be calculated using the linear trapezoidal method
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
Quantifiable serum concentrations are only available for the 50mg SAD and MAD cohort. For the PK parameters of the SAD 6.25, 12.5 and 25mg cohorts, no quantifiable serum concentrations could be measured. For the 6.25, 12.5 and 25mg MAD cohorts, no PK profiling was performed due to the large number of samples below the limit of detection.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 4 0 0 0 0 6 0
Mean (Standard Deviation)
Unit of Measure: ng.hr/mL
Dose 1 17.2  (8.2) 19.0  (15.6)
Week 4, Dose 12 NA [1]   (NA) 17.0  (11.4)
[1]
for SAD cohorts, there is no Week 4, Dose 12 timepoint
9.Secondary Outcome
Title Area Under the Curve to Infinity [AUC(0-∞)]
Hide Description AUC0-∞: Area under the curve to infinity will be calculated based on the last observed concentration Clast(obs) using formula: AUC0-∞=AUClast+Clast(obs)/λz
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The Area Under the Curve to Infinity is not reported because the %AUC extrapolation was too large
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Serum Clearance (CL)
Hide Description CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.
Time Frame 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Hide Outcome Measure Data
Hide Analysis Population Description
The Serum Clearance is not reported because the %AUC extrapolation was too large.
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in CFQ-R RSS
Hide Description Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.
Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description

All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses.

For 1 subject in the placebo group no data were available at Day 54. "Mean" in this table refers to "Adjusted Mean".

Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 6 5 8
Mean (Standard Error)
Unit of Measure: score on a scale
Day 15 Number Analyzed 6 participants 6 participants 6 participants 5 participants 8 participants
-4.13  (4.10) 8.95  (4.12) 7.76  (4.15) -0.80  (4.51) -5.09  (3.59)
Day 33 Number Analyzed 6 participants 6 participants 6 participants 5 participants 8 participants
6.43  (4.92) 12.65  (4.93) 7.76  (4.96) -3.02  (5.40) -6.48  (4.29)
Day 54 Number Analyzed 6 participants 6 participants 6 participants 5 participants 7 participants
-10.24  (6.56) 0.61  (6.57) 5.91  (6.59) -4.13  (7.20) -10.31  (5.87)
12.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo
Hide Description

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS).

A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.

Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses.
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Overall Number of Participants Analyzed 6 6 6 5
Mean (Standard Error)
Unit of Measure: score on a scale
Day 15 0.96  (5.46) 14.03  (5.49) 12.85  (5.55) 4.29  (5.73)
Day 33 12.91  (6.53) 19.13  (6.56) 14.24  (6.60) 3.46  (6.87)
Day 54 0.07  (8.81) 10.92  (8.83) 16.22  (8.87) 6.18  (9.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 6.25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0592
Comments p-values are presented for Day 33.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 12.91
Confidence Interval (2-Sided) 95%
-0.54 to 26.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 12.5 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments p-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 19.13
Confidence Interval (2-Sided) 95%
5.62 to 32.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0408
Comments p-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 14.24
Confidence Interval (2-Sided) 95%
0.64 to 27.83
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 50 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6193
Comments p-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 3.46
Confidence Interval (2-Sided) 95%
-10.69 to 17.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.87
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in CFQ-R RSS (Subgroup ppFEV1 <90% at Baseline)
Hide Description

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS).

A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.

Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description

Subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses, with ppFEV1 <90% at baseline.

For 1 subject in the placebo group no data were available at Day 54. "Mean" in this table refers to "Adjusted Mean".

Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 3 4 5 4 4
Mean (Standard Error)
Unit of Measure: score on a scale
Day 15 Number Analyzed 3 participants 4 participants 5 participants 4 participants 4 participants
-3.37  (5.51) 8.64  (4.87) 9.56  (4.28) -0.87  (4.79) -4.77  (4.82)
Day 33 Number Analyzed 3 participants 4 participants 5 participants 4 participants 4 participants
11.45  (7.36) 15.58  (6.44) 8.44  (5.71) -0.87  (6.38) -11.72  (6.41)
Day 54 Number Analyzed 3 participants 4 participants 5 participants 4 participants 3 participants
-3.37  (6.36) 5.86  (5.59) 7.33  (4.94) -3.65  (5.52) -6.49  (6.33)
14.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)
Hide Description

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS).

A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.

Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses, with ppFEV1 <90% at Baseline.
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Overall Number of Participants Analyzed 3 4 5 4
Mean (Standard Error)
Unit of Measure: score on a scale
Day 15 1.41  (7.29) 13.41  (6.95) 14.33  (6.49) 3.90  (6.74)
Day 33 23.17  (9.73) 27.30  (9.17) 20.16  (8.62) 10.84  (9.01)
Day 54 3.12  (8.93) 12.35  (8.58) 13.82  (8.08) 2.84  (8.33)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 6.25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0321
Comments p-values are presented for Day 33.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 23.17
Confidence Interval (2-Sided) 95%
2.29 to 44.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 9.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 12.5 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0100
Comments p-values are presented for Day 33.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 27.30
Confidence Interval (2-Sided) 95%
7.64 to 46.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 9.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0346
Comments p-values are presented for Day 33.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 20.16
Confidence Interval (2-Sided) 95%
1.68 to 38.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 50 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline CFQ-R RSS as outcome variable and including treatment, baseline CFQ-R RSS value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2485
Comments p-values are presented for Day 33.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 10.84
Confidence Interval (2-Sided) 95%
-8.47 to 30.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 9.01
Estimation Comments [Not Specified]
15.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in ppFEV1
Hide Description Exploratory efficacy parameter, as measured by spirometry, and expressed in percent predicted FEV1 (ppFEV1). Mean values reported refer to ''adjusted mean change from baseline'' values.
Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses.
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 6 6 6 5 8
Mean (Standard Error)
Unit of Measure: percentage of predicted
(pre-dose) Day 15 0.06  (1.96) 2.50  (1.96) -4.03  (1.96) -1.85  (2.14) -0.83  (1.70)
(pre-dose) Day 26 0.46  (2.64) 3.22  (2.64) -0.98  (2.64) -1.39  (2.89) -0.80  (2.28)
Day 33 1.54  (2.40) 0.05  (2.40) -2.17  (2.40) -3.21  (2.63) -2.70  (2.08)
Day 54 1.68  (2.88) -1.63  (2.88) 0.61  (2.88) -2.43  (3.15) -2.58  (2.49)
16.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo
Hide Description Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1 (ppFEV1). Mean values reported refer to''difference vs placebo in adjusted mean change from baseline'' values.
Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses.
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Overall Number of Participants Analyzed 6 6 6 5
Mean (Standard Error)
Unit of Measure: percentage of predicted
Day 15 0.89  (2.59) 3.32  (2.59) -3.20  (2.59) -1.02  (2.73)
Day 26 1.26  (3.49) 4.02  (3.49) -0.17  (3.49) -0.59  (3.68)
Day 33 4.24  (3.18) 2.75  (3.18) 0.53  (3.18) -0.51  (3.35)
Day 54 4.26  (3.81) 0.96  (3.80) 3.20  (3.81) 0.15  (4.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 6.25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline ppFEV1 as outcome variable and including treatment, baseline ppFEV1 value, time and interaction between time and treatment as covariate
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1938
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 4.24
Confidence Interval (2-Sided) 95%
-2.30 to 10.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 12.5 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline ppFEV1 as outcome variable and including treatment, baseline ppFEV1 value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3943
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 2.75
Confidence Interval (2-Sided) 95%
-3.79 to 9.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 25 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline ppFEV1 as outcome variable and including treatment, baseline ppFEV1 value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8688
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-6.01 to 7.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 50 mg
Comments A mixed-model analysis was performed with repeated time measures on the change from baseline ppFEV1 as outcome variable and including treatment, baseline ppFEV1 value, time and interaction between time and treatment as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8813
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter difference vs placebo
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-7.41 to 6.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.35
Estimation Comments [Not Specified]
17.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in ppFEV1 (Subgroup ppFEV1 <90% at Baseline)
Hide Description Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''adjusted mean change from baseline'' values.
Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses, with ppFEV1 <90% at Baseline..
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

Overall Number of Participants Analyzed 3 4 5 4 4
Mean (Standard Error)
Unit of Measure: percentage of predicted
Day 15 -0.29  (2.22) 4.54  (1.92) -3.45  (1.71) -1.01  (1.91) -3.40  (1.95)
Day 26 4.21  (4.05) 7.15  (3.51) 0.89  (3.13) -0.10  (3.50) -3.76  (3.52)
Day 33 6.01  (3.16) 3.81  (2.74) -0.68  (2.44) -0.97  (2.73) -4.18  (2.76)
18.Other Pre-specified Outcome
Title Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)
Hide Description Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.
Time Frame Day 15, Day 33, Day 54
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects treated with either QR-010 or placebo in the Multiple Ascending Dose cohorts that received at least 10 out of 12 doses, with ppFEV1 <90% at Baseline.
Arm/Group Title QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg
Hide Arm/Group Description:

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Overall Number of Participants Analyzed 3 4 5 4
Mean (Standard Error)
Unit of Measure: percentage of predicted
Day 15 3.11  (2.99) 7.93  (2.76) -0.05  (2.59) 2.38  (2.74)
Day 26 7.97  (5.39) 10.90  (4.98) 4.65  (4.71) 3.65  (4.97)
Day 33 10.19  (4.22) 7.99  (3.91) 3.50  (3.69) 3.21  (3.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 6.25 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0301
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 10.19
Confidence Interval (2-Sided) 95%
1.13 to 19.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 12.5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0601
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 7.99
Confidence Interval (2-Sided) 95%
-0.39 to 16.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 25 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3580
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 3.50
Confidence Interval (2-Sided) 95%
-4.40 to 11.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection QR-010 MAD 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4224
Comments P-values are presented for Day 33
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference vs placebo
Estimated Value 3.21
Confidence Interval (2-Sided) 95%
-5.13 to 11.55
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.89
Estimation Comments [Not Specified]
Time Frame For the SAD cohorts, from randomization up to Day 8 after dose administration. For the MAD cohorts, from randomization for at least 30 days after the last administration of the study treatment.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Hide Arm/Group Description

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation as a single dose

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation as a single dose

Placebo: Normal Saline

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

QR-010 administered via inhalation three times weekly for four weeks.

QR-010: Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo (normal saline) administered via inhalation three times weekly for four weeks.

Placebo: Normal Saline

All-Cause Mortality
QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/7 (0.00%)      0/6 (0.00%)      0/9 (0.00%)    
Hide Serious Adverse Events
QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/7 (0.00%)      1/6 (16.67%)      1/9 (11.11%)    
Gastrointestinal disorders                     
Abdominal Pain * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1
Infections and infestations                     
Respiratory Tract Infection * 2  0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/9 (0.00%)  0
Renal and urinary disorders                     
Calculus Urinary * 2  0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/9 (0.00%)  0
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/6 (50.00%)      2/6 (33.33%)      7/9 (77.78%)      4/6 (66.67%)      2/9 (22.22%)      5/6 (83.33%)      5/6 (83.33%)      6/7 (85.71%)      5/6 (83.33%)      9/9 (100.00%)    
Gastrointestinal disorders                     
Dry Mouth * 2  2/6 (33.33%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Diarrhoea * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%) 
Abdominal pain upper * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%) 
General disorders                     
Fatigue * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%) 
Pyrexia * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/7 (28.57%)  0/6 (0.00%)  1/9 (11.11%) 
Chest pain * 2 [1]  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%) 
Chest discomfort * 2 [1]  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%) 
Infections and infestations                     
Oral candidiasis * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%) 
Respiratory Tract Infection * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/9 (0.00%) 
Rhinitis * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Injury, poisoning and procedural complications                     
Sunburn * 2  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Investigations                     
Forced expiratory volume decreased * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  2/9 (22.22%) 
Metabolism and nutrition disorders                     
Hyperglycaemia * 2  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Arthralgia * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%) 
Nervous system disorders                     
Headache * 1  1/6 (16.67%)  1/6 (16.67%)  2/9 (22.22%)  1/6 (16.67%)  1/9 (11.11%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Dizziness * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Psychiatric disorders                     
Agitation * 2  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Respiratory tract congestion * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Sputum increased * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  3/9 (33.33%) 
Nasal congestion * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%) 
Oropharyngeal pain * 2  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%) 
Cough * 2  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  1/6 (16.67%)  0/9 (0.00%)  3/6 (50.00%)  1/6 (16.67%)  0/7 (0.00%)  2/6 (33.33%)  2/9 (22.22%) 
Wheezing * 2  0/6 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/6 (0.00%)  0/9 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
Skin and subcutaneous tissue disorders                     
Pruritus generalised * 2  0/6 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%) 
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
[1]
General disorders and administration site conditions
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.
Investigators are restricted from disclosure or results until after multicenter 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 45 days (varying per site). Sponsor may request redaction of confidential information.
Results Point of Contact
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Name/Title: Medical Monitor
Organization: ProQR Therapeutics
Phone: +31 6 20 183 437
EMail: clinical@proqr.com
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Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT02532764    
Other Study ID Numbers: PQ-010-001
First Submitted: August 13, 2015
First Posted: August 26, 2015
Results First Submitted: December 11, 2018
Results First Posted: February 6, 2019
Last Update Posted: February 6, 2019