Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients
- Registration Number
- NCT02532764
- Lead Sponsor
- ProQR Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
- 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
- Breast-feeding or pregnant
- Use of lumacaftor or ivacaftor
- Use of any investigational drug or device
- History of lung transplantation
- Hemoptysis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks. QR-010 QR-010 QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.
- Primary Outcome Measures
Name Time Method Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit. 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.
Severity of Treatment Emergent Adverse Events From Baseline Through End of Study 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Assessment of severity of treatment emergent adverse events (TEAEs).
Severity is graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Modified for CF (CTCAE v4.03). For events not present in this listing the following grading was applied:
Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Moderate: Minimal, local, or noninvasive intervention indicated; discomfort sufficient to reduce or interfere with daily activities; Severe: Medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization may be indicated; disabling; limits self-care with significant interference with daily activities; incapacitating with inability to perform self care activities of daily living; Life-threatening: Urgent intervention indicated; immediate risk of death.Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)
- Secondary Outcome Measures
Name Time Method Time to Maximum Serum Concentration 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Tmax: Time to Cmax of QR-010 serum concentrations.
Area Under the Curve to Infinity [AUC(0-∞)] 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts AUC0-∞: Area under the curve to infinity will be calculated based on the last observed concentration Clast(obs) using formula: AUC0-∞=AUClast+Clast(obs)/λz
Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings. 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Number of subjects experiencing at least one abnormality for the categories laboratory parameters, vital signs, ECG, spirometry and physical findings that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely.
Maximum Serum Concentration 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Cmax: QR-010 maximum serum concentrations
Terminal Half-life (T1/2) 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts The terminal elimination half-life will be estimated by non-linear regression analysis of the terminal elimination slope
Area Under the Curve to Final Sample [AUC(0-last)] 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts Area under the curve to the final sample with a concentration greater than lower limit of quantification (LLQ) will be calculated using the linear trapezoidal method
Serum Clearance (CL) 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.
Trial Locations
- Locations (27)
University of Southern California USC - Keck School of Medicine
🇺🇸Los Angeles, California, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Motol University Hospital
🇨🇿Prague, Czechia
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Cystic Fibrosis Center Rigshospitalet
🇩🇰Copenhagen, Denmark
Hopital Necker- Enfants Malades
🇫🇷Paris, France
HGRL Chu Nantes
🇫🇷Nantes, France
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Munich U. Hospital, Cystic Fibrosis Center for Adults
🇩🇪Munich, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hospital Vall D'Hebron
🇪🇸Barcelona, Spain
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Universitair Ziekenhuis Brussel
🇧🇪Brussels, Belgium
University of Leuven
🇧🇪Leuven, Belgium
Celerion
🇬🇧Belfast, Northern Ireland, United Kingdom
University of Calgary (Health Sciences Centre)
🇨🇦Calgary, Alberta, Canada
University of Kansas Medical Center Research Institute
🇺🇸Kansas City, Kansas, United States
Azienda Ospedaliera Universitaria Integrata di Verona
🇮🇹Verona, Italy
Stanford University
🇺🇸Palo Alto, California, United States
Royal Brompton Hospital
🇬🇧London, United Kingdom