Title
Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients
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
Phase
Phase 1/Phase 2Lead Sponsor
ProQR TherapeuticsStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Cystic FibrosisIntervention/Treatment
qr-010 ...Study Participants
70A randomized, double-blind, placebo-controlled study of single and multiple ascending doses of QR-010 in adults homozygous for ΔF508 Cystic Fibrosis.
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.
Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton
Normal Saline
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
| Event Type | Organ System | Event Term | QR-010 SAD 6.25 mg | QR-010 SAD 12.5 mg | QR-010 SAD 25 mg | QR-010 SAD 50 mg | Placebo SAD | QR-010 MAD 6.25 mg | QR-010 MAD 12.5 mg | QR-010 MAD 25 mg | QR-010 MAD 50 mg | Placebo MAD |
|---|
Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)
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.
DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.
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.
Cmax: QR-010 maximum serum concentrations
Tmax: Time to Cmax of QR-010 serum concentrations.
The terminal elimination half-life will be estimated by non-linear regression analysis of the terminal elimination slope
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
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
CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.
Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.
Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.
Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.
Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.
Exploratory efficacy parameter, as measured by spirometry, and expressed in percent predicted FEV1 (ppFEV1). Mean values reported refer to ''adjusted mean change from baseline'' values.
Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1 (ppFEV1). Mean values reported refer to''difference vs placebo in adjusted mean change from baseline'' values.
Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''adjusted mean change from baseline'' values.
Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.
