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

• ClinicalTrials.gov Identifier: NCT02564354
• Recruitment Status: Completed
• First Posted: September 30, 2015
• Last Update Posted: November 10, 2016
• Sponsor: ProQR Therapeutics
• Collaborator: European Commission
• Information provided by (Responsible Party): ProQR Therapeutics

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: QR-010	Phase 1

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: September 2015
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: ΔF508 Homozygous; QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.	Drug: QR-010; Single-stranded RNA antisense oligonucleotide in isoosmolar solution
Experimental: ΔF508 Compound Heterozygous; QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.	Drug: QR-010; Single-stranded RNA antisense oligonucleotide in isoosmolar solution

Outcome Measures

Primary Outcome Measures :

1. Intra-subject change of CFTR-mediated total chloride 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 ]
   Exploratory Efficacy

Secondary Outcome Measures :

1. 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: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment ]
   Key Exploratory Efficacy
2. Compare CFTR-mediated total chloride transport between dF508 homozygous and compound heterozygous CF subjects from baseline through End of Study [ Time Frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment ]
   Exploratory Efficacy
3. Incidence of (serious) adverse events from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability
4. Incidence of discontinuations due to AEs from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability
5. Abnormalities of laboratory parameters (chemistry, hematology and urinalysis) from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability
6. Abnormalities of vital signs & oximetry from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability
7. Abnormalities of physical examinations from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability
8. Changes in nasal symptoms (based on the NERS and SNOT-22) from baseline through End of Study [ Time Frame: 3 weeks post-treatment ]
   Safety and tolerability

Other Outcome Measures:

1. Serum concentration of QR-010 after intranasal administration [ Time Frame: 30 minutes post dose Baseline, 2 & 4 weeks ]
   Pharmacokinetics
2. Serum concentration of QR-010 after intranasal administration if persistent AE(s) are present [ Time Frame: 3 weeks post-treatment ]
   Pharmacokinetics
3. Changes in systemic effect of QR-010 as measured by pilocarpine iontopheresis sweat chloride [ Time Frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment ]
   Pharmacokinetics
4. Explore correlation between change in nasal potential difference (NPD), sweat chloride (mmol/L), and serum concentration of QR-010 [ Time Frame: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment ]
   Exploratory Efficacy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Ohio

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Belgium

U.Z. Leuven

Leuven, Belgium, 3000

France

Hopital Necker-Enfants Malades

Paris, France, 75743

Sponsors and Collaborators

ProQR Therapeutics

European Commission

Investigators

• Principal Investigator: John P Clancy, MD; Cincinnati Childrens Hospital Medical Center

More Information

• Responsible Party: ProQR Therapeutics
• ClinicalTrials.gov Identifier: NCT02564354 History of Changes
• Other Study ID Numbers: PQ-010-002
• First Posted: September 30, 2015
• Last Update Posted: November 10, 2016
• Last Verified: November 2016

Keywords provided by ProQR Therapeutics:

Cystic Fibrosis; CF; ΔF508; CFTR; QR-010; antisense oligonucleotide; RNA therapy; F508del; NPD; nasal potential difference

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases