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

NCT02564354 | Completed Phase 1 Results DMC

• 1 other identifier: PQ-010-002
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 5

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).

Conditions

Cystic Fibrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.

• The Mean Change in CFTR-mediated Total Chloride Transport.

  2 and 4 weeks, and at 3 weeks post-treatment.

• Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study.

  3 weeks post-treatment.

Study Arms (2)

ΔF508 Homozygous

EXPERIMENTAL

QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.

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.

Drug: QR-010

Interventions

QR-010 DRUG

Single-stranded RNA antisense oligonucleotide in isoosmolar solution

ΔF508 Compound Heterozygous; ΔF508 Homozygous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ProQR Therapeutics: lead
• European Commission: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

U.Z. Leuven

Leuven, 3000, Belgium

Location

Hopital Necker-Enfants Malades

Paris, 75743, France

Location

Related Publications (1)

• 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.

  PMID: 31215818 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

eluforsen

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: ProQR Therapeutics

clinical@proqr.com

+31 6 20 183 437

Study Officials

• John P Clancy, MD

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2015
• First Posted: September 30, 2015
• Study Start: September 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 24, 2020
• Results First Posted: September 24, 2020

Record last verified: 2020-09

Locations

FR (1); US (3); BE (1)