Clinical trial NCT02532764: Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients
Official title: Phase 1b, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of QR-010 in Subjects With Homozygous ΔF508 Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
ΔF508
RNA therapies
antisense oligonucleotide
CFTR
F508del
CF
RNA therapy
Lead sponsor: ProQR Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: European Commission
First posted: 2015-08-26
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A randomized, double-blind, placebo-controlled study of single and multiple ascending doses of QR-010 in adults homozygous for ΔF508 Cystic Fibrosis.

Detailed description: The purpose of this study is to evaluate the safety, tolerability, and to determine the pharmacokinetics of QR-010 administered via inhalation in adult homozygous for ΔF508 Cystic Fibrosis.

Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of \> 60 mmol/L
* Confirmation of CFTR gene mutations homozygous for the ΔF508 mutation
* Body mass index (BMI) ≥ 17 kg/m2
* Non-smoking for a minimum of two years
* FEV1 ≥70% of predicted normal for age, gender, and height, at Screening
* Stable lung function
* Adequate hepatic and renal function

Exclusion Criteria:

* Breast-feeding or pregnant
* Use of lumacaftor or ivacaftor
* Use of any investigational drug or device
* History of lung transplantation
* Hemoptysis

Primary outcomes:
measure: Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Severity of Treatment Emergent Adverse Events From Baseline Through End of Study
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit.
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Secondary outcomes:
measure: Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings.
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Maximum Serum Concentration
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Time to Maximum Serum Concentration
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Terminal Half-life (T1/2)
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Area Under the Curve to Final Sample [AUC(0-last)]
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Area Under the Curve to Infinity [AUC(0-∞)]
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
measure: Serum Clearance (CL)
timeFrame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Other outcomes:
measure: Adjusted Mean Change From Baseline in CFQ-R RSS
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in CFQ-R RSS (Subgroup ppFEV1 <90% at Baseline)
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in ppFEV1
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in ppFEV1 (Subgroup ppFEV1 <90% at Baseline)
timeFrame: Day 15, Day 33, Day 54
measure: Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)
timeFrame: Day 15, Day 33, Day 54
Locations:
city: Los Angeles
country: United States
facility: University of Southern California USC - Keck School of Medicine
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Leuven
country: Belgium
facility: University of Leuven
city: Calgary
country: Canada
facility: University of Calgary (Health Sciences Centre)
state: Alberta
city: Prague
country: Czechia
facility: Motol University Hospital
city: Copenhagen
country: Denmark
facility: Cystic Fibrosis Center Rigshospitalet
city: Nantes
country: France
facility: HGRL Chu Nantes
city: Paris
country: France
facility: Hopital Necker- Enfants Malades
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Munich
country: Germany
facility: Munich U. Hospital, Cystic Fibrosis Center for Adults
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Belfast
country: United Kingdom
facility: Celerion
state: Northern Ireland
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Trust and Queen's University Belfast
name: Stuart Elborn, 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.