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Completed

NCT Number: NCT02532764

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

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

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Universitair Ziekenhuis Brussel, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

QR-010

Drug

Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Placebo

Drug

Normal Saline

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

ProQR Therapeutics

Industry

Collaborators

  • European Commission

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Aug 26, 2015
Registry last updated
Feb 6, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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