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

September 2, 2020 updated by: ProQR Therapeutics

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, multi-center, exploratory study to estimate the effect of intranasal administration of QR-010 on the nasal mucosa in the restoration of CFTR function, as measured by nasal potential difference (NPD), in the nasal epithelium of adult subjects with CF who are homozygous or compound heterozygous for the ΔF508 CFTR mutation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • U.Z. Leuven
  • France
      • Paris, France, 75743
        • Hôpital Necker-Enfants Malades
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish Health
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of > 60 mmol/L
  • Nasal potential difference (NPD) measurement at Screening consistent with CF
  • Confirmation of CFTR gene mutations homozygous or compound heterozygous for the ΔF508 mutation
  • Body mass index (BMI) of ≥ 18 kg/m2
  • Non-smoking for a minimum of 2 years
  • Stable lung function
  • FEV1 ≥40% of predicted normal for age, gender, and height at Screening

Exclusion Criteria:

  • Breast-feeding or pregnant
  • Acute allergy or infection affecting nasal conditions not resolved within 14 days prior Screening
  • Use of lumacaftor or ivacaftor
  • Use of any investigational drug or device
  • Hemoptysis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ΔF508 Homozygous
QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
Drug: QR-010
Single-stranded RNA antisense oligonucleotide in isoosmolar solution
Experimental: ΔF508 Compound Heterozygous
QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
Drug: QR-010
Single-stranded RNA antisense oligonucleotide in isoosmolar solution

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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).
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.
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.
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.
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.
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.
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.
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 subjects experiencing serious adverse events from baseline through End of Study.
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 subject discontinuations due to AEs from baseline through End of Study. No discontinuations occurred.
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 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.
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 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.
3 weeks post-treatment.
Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study.
Time Frame: 3 weeks post-treatment.
Number of subjects experiencing at least one abnormality in physical examination that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely, from baseline through End of Study.
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.
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.
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.
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.
3 weeks post-treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ProQR Therapeutics

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European Commission

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John P Clancy, MD, Cincinnati Childrens Hospital Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 30, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 24, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PQ-010-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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