Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02532764
Recruitment Status : Completed
First Posted : August 26, 2015
Results First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
ProQR Therapeutics

Tracking Information
First Submitted Date  ICMJE August 13, 2015
First Posted Date  ICMJE August 26, 2015
Results First Submitted Date December 11, 2018
Results First Posted Date February 6, 2019
Last Update Posted Date February 6, 2019
Study Start Date  ICMJE June 2015
Actual Primary Completion Date September 14, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)
  • Severity of Treatment Emergent Adverse Events From Baseline Through End of Study [ Time Frame: 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 Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit. [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • Incidence of adverse events from baseline through End of Study Visit [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety and Tolerability
  • Severity of adverse events from baseline through End of Study [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety and Tolerability
  • Occurrence of dose-limiting toxicities (DLT) in each dose cohort from baseline through End of Study Visit. [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety and Tolerability
Change History Complete list of historical versions of study NCT02532764 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings. [ Time Frame: 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 [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Cmax: QR-010 maximum serum concentrations
  • Time to Maximum Serum Concentration [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Tmax: Time to Cmax of QR-010 serum concentrations.
  • Terminal Half-life (T1/2) [ Time Frame: 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)] [ Time Frame: 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
  • Area Under the Curve to Infinity [AUC(0-∞)] [ Time Frame: 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
  • Serum Clearance (CL) [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • Changes from baseline to end-of-treatment or presence of abnormalities regarding laboratory parameters, vital signs, ECG, spirometry, and physical findings. [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety
  • Changes from baseline to end-of-treatment or presence of abnormalities regarding laboratory parameters using descriptive statistics, shift tables, and frequencies and percentage of subjects with treatment emergent abnormalities for each timepoint. [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety
  • Changes from baseline to end-of-treatment or presence of abnormalities in vital signs will be summarized descriptively. [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety
  • Changes from baseline to end-of-treatment or presence of abnormalities regarding ECG, spirometry, and physical findings will be summarized and listed as specified in the Statistical Analysis Plan. [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Safety
  • Maximum Serum Concentration (Cmax) [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
  • Time to Maximum Serum Concentration (Tmax) [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
  • Terminal Half-life (T1/2) [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
  • Area Under the Curve to Final Sample [AUC(0-last)] [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
  • Area Under the Curve to Infinity [AUC(0-∞)] [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
  • Serum Clearance (CL) [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Pharmacokinetics
Current Other Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Adjusted Mean Change From Baseline in CFQ-R RSS [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in CFQ-R RSS (Subgroup ppFEV1 <90% at Baseline) [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline) [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in ppFEV1 [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
  • Adjusted Mean Change From Baseline in ppFEV1 (Subgroup ppFEV1 <90% at Baseline) [ Time Frame: Day 15, Day 33, Day 54 ]
    Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''adjusted mean change from baseline'' values.
  • Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline) [ Time Frame: Day 15, Day 33, Day 54 ]
    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.
Original Other Outcome Measures  ICMJE
 (submitted: August 21, 2015)
  • Change in FEV1 [ Time Frame: 8 weeks for Multiple-dose cohorts ]
    Exploratory Efficacy
  • Change in patient reported outcome measure CFQ-R Respiratory Symptom Score (CFQ-R RSS) [ Time Frame: 8 weeks for Multiple-dose cohorts ]
    Exploratory Efficacy
  • Change in body weight [ Time Frame: 8 weeks for Multiple-dose cohorts ]
    Exploratory Efficacy
  • Change in Sweat chloride [ Time Frame: 8 weeks for Multiple-dose cohorts ]
    Exploratory Efficacy
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • Drug: QR-010
    Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton
  • Drug: Placebo
    Normal Saline
Study Arms
  • Experimental: QR-010
    QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.
    Intervention: Drug: QR-010
  • Placebo Comparator: Placebo
    Placebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2019)
70
Original Estimated Enrollment  ICMJE
 (submitted: August 21, 2015)
64
Actual Study Completion Date September 14, 2017
Actual Primary Completion Date September 14, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   Denmark,   France,   Germany,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02532764
Other Study ID Numbers  ICMJE PQ-010-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party ProQR Therapeutics
Study Sponsor  ICMJE ProQR Therapeutics
Collaborators  ICMJE European Commission
Investigators  ICMJE
Principal Investigator: Stuart Elborn, MD Trust and Queen's University Belfast
PRS Account ProQR Therapeutics
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP