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Trial record 2 of 2 for:    QR010

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

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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

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: QR-010 Drug: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : June 2015
Actual Primary Completion Date : September 14, 2017
Actual Study Completion Date : September 14, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: QR-010
QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.
Drug: QR-010
Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo Comparator: Placebo
Placebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks.
Drug: Placebo
Normal Saline




Primary Outcome Measures :
  1. 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)

  2. 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.


  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. Maximum Serum Concentration [ Time Frame: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts ]
    Cmax: QR-010 maximum serum concentrations

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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-∞.


Other Outcome Measures:
  1. 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.

  2. 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.


  3. 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.


  4. 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.


  5. 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.

  6. 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.

  7. 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.

  8. 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.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02532764


  Show 27 Study Locations
Sponsors and Collaborators
ProQR Therapeutics
European Commission
Investigators
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Principal Investigator: Stuart Elborn, MD Trust and Queen's University Belfast
  Study Documents (Full-Text)

Documents provided by ProQR Therapeutics:
Study Protocol  [PDF] April 4, 2017
Statistical Analysis Plan  [PDF] April 18, 2017


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Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT02532764     History of Changes
Other Study ID Numbers: PQ-010-001
First Posted: August 26, 2015    Key Record Dates
Results First Posted: February 6, 2019
Last Update Posted: February 6, 2019
Last Verified: January 2019
Keywords provided by ProQR Therapeutics:
cystic fibrosis
ΔF508
RNA therapies
antisense oligonucleotide
CFTR
F508del
CF
RNA therapy
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases