Clinical trial NCT02564354: Exploratory Study to Evaluate QR-010 in Subjects With Cystic Fibrosis ΔF508 CFTR Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
CF
ΔF508
CFTR
QR-010
antisense oligonucleotide
RNA therapy
F508del
NPD
nasal potential difference
Lead sponsor: ProQR Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: European Commission
First posted: 2015-09-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Exploratory proof of concept study to determine whether intranasal administration of QR-010 in subjects with cystic fibrosis, homozygous or compound heterozygous for the ΔF508 mutation, can increase the function of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
timeFrame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
Secondary outcomes:
measure: 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.
timeFrame: 2 and 4 weeks, and at 3 weeks post-treatment.
measure: 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.
timeFrame: 2 and 4 weeks, and at 3 weeks post-treatment.
measure: Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study.
timeFrame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
measure: The Mean Change in CFTR-mediated Total Chloride Transport.
timeFrame: 2 and 4 weeks, and at 3 weeks post-treatment.
measure: Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Number of Subject Discontinuations Due to AEs From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
measure: Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study.
timeFrame: 3 weeks post-treatment.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Leuven
country: Belgium
facility: U.Z. Leuven
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
Study officials:
affiliation: Cincinnati Childrens Hospital Medical Center
name: John P Clancy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.