Exploratory Study to Evaluate QR-010 in Subjects With Cystic Fibrosis ΔF508 CFTR Mutation

A Phase 1 study testing QR-010 in people with Cystic Fibrosis, run by ProQR Therapeutics at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cystic Fibrosis
What is being tested?: QR-010
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 5 sitesin 3 countries
Study dates: Sep 2015to Sep 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

5 sites in 3 countries.

Country

City, postcode or hospital

5 sites in 3 countries

United States3 sites

University of Alabama at Birmingham
Birmingham, Alabama, 35233
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, 45229
National Jewish Health
Denver, Colorado, 80206

Other trials in United States

Belgium1 site

U.Z. Leuven
Leuven, 3000

Other trials in Belgium

France1 site

Hopital Necker-Enfants Malades
Paris, 75743

Other trials in France

About this study

Official title: Open-Label, Exploratory Study to Evaluate the Effects of QR-010 on Nasal Potential Difference in Subjects With CF With the ΔF508 CFTR Mutation

Read the 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.

Conditions: Cystic Fibrosis
Being tested: QR-010
Keywords: Cystic Fibrosis, CF, ΔF508, CFTR, QR-010, antisense oligonucleotide, RNA therapy, F508del, NPD, nasal potential difference
Medical subject headings: Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

QR-010Drug
Single-stranded RNA antisense oligonucleotide in isoosmolar solution

Study groups in NCT02564354
Study group	Role	What they receive
ΔF508 Homozygous	Experimental	QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks. Receives: Drug: QR-010
ΔF508 Compound Heterozygous	Experimental	QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks. Receives: Drug: QR-010

What is being measured

The primary outcome is the main question the study is designed to answer.

Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
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.
Measured: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.

Secondary outcomes (11)

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.
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).
Measured: 2 and 4 weeks, and at 3 weeks post-treatment.
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.
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.
Measured: 2 and 4 weeks, and at 3 weeks post-treatment.
Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study.
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.
Measured: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
The Mean Change in CFTR-mediated Total Chloride Transport.
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.
Measured: 2 and 4 weeks, and at 3 weeks post-treatment.
Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study.
Number of subjects experiencing serious adverse events from baseline through End of Study.
Measured: 3 weeks post-treatment.
Number of Subject Discontinuations Due to AEs From Baseline Through End of Study.
Number of subject discontinuations due to AEs from baseline through End of Study. No discontinuations occurred.
Measured: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study.
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.
Measured: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study.
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.
Measured: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study.
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.
Measured: 3 weeks post-treatment.
Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study.
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.
Measured: 3 weeks post-treatment.
Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study.
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.
Measured: 3 weeks post-treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2015Sep 2016

First posted30 Sep 2015 (estimated)
Study startSep 2015
Primary completionSep 2016
Study completionSep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cystic FibrosisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02564354
Sponsor's protocol ID: PQ-010-002
Status last verified: Sep 2020
First submitted: 29 Sep 2015
Last updated: 24 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.
PubMed 31215818

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cystic Fibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-Label, Exploratory Study to Evaluate the Effects of QR-010 on Nasal Potential Difference in Subjects With CF With the ΔF508 CFTR Mutation
ClinicalTrials.gov ID: NCT02564354
Acronym / sponsor ID: PQ-010-002
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis, CF, ΔF508, CFTR, QR-010, antisense oligonucleotide, RNA therapy, F508del
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: ProQR TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: European Commission
Study start: Sep 2015
Primary completion: Sep 2016 (actual)
Study completion: Sep 2016 (actual)
First posted: 30 Sep 2015 (estimated)
Results: Posted 24 Sep 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ΔF508 Homozygous	Experimental	Drug: QR-010QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
ΔF508 Compound Heterozygous	Experimental	Drug: QR-010QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
QR-010Single-stranded RNA antisense oligonucleotide in isoosmolar solution	Drug	ΔF508 Compound Heterozygous, ΔF508 Homozygous

Primary outcome

Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
Time frame: 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.

11 secondary outcomes

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.
Time frame: 2 and 4 weeks, and at 3 weeks post-treatment.
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.
Time frame: 2 and 4 weeks, and at 3 weeks post-treatment.
Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study.
Time frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
The Mean Change in CFTR-mediated Total Chloride Transport.
Time frame: 2 and 4 weeks, and at 3 weeks post-treatment.
Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Number of Subject Discontinuations Due to AEs From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.
Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study.
Time frame: 3 weeks post-treatment.

Results and safety

Results posted to the registry on 24 Sep 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Homozygous for the F508del-CFTR Mutation	10	10
Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation	8	8

Primary outcome: Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).

Time frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.. Mean (Standard Deviation). Unit: mV

Measure	Cohort 1: Homozygous for the F508del-CFTR Mutation n = 7	Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation n = 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)

Population analysed: 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.

11 secondary outcomes are reported in the full results.

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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: Homozygous for the F508del-CFTR Mutation	0 of 10 (0%)	9 of 10 (90%)	0 of 10
Cohort 2: Compound Heterozygous for the F508del-CFTR Mutation	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31215818Miah KM, Hyde SC, Gill DR. Emerging gene therapies for cystic fibrosis. Expert Rev Respir Med. 2019 Aug;13(8):709-725. doi: 10.1080/17476348.2019.1634547. Epub 2019 Jun 27.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John P Clancy, MD principal investigator

Cincinnati Childrens Hospital Medical Center

5 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing QR-010 in people with Cystic Fibrosis, run by ProQR Therapeutics at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Belgium, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD). (time frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02564354, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2020.