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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

QR-010

Placebo

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis, ΔF508, RNA therapies, antisense oligonucleotide, CFTR, F508del, CF, RNA therapy

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Southern California USC - Keck School of Medicine
Stanford University
Northwestern University
University of Kansas Medical Center Research Institute
Massachusetts General Hospital
Boston Children's Hospital
Washington University School of Medicine
Nationwide Children's Hospital
Penn State Milton S. Hershey Medical Center
Medical University of South Carolina
University of Texas Southwestern Medical Center
University of Washington Medical Center
Universitair Ziekenhuis Brussel
University of Leuven
University of Calgary (Health Sciences Centre)
Motol University Hospital
Cystic Fibrosis Center Rigshospitalet
HGRL Chu Nantes
Hopital Necker- Enfants Malades
Charité Universitätsmedizin Berlin
Medizinische Hochschule Hannover
Munich U. Hospital, Cystic Fibrosis Center for Adults
Azienda Ospedaliera Universitaria Integrata di Verona
Hospital Vall D'Hebron
Celerion
Royal Brompton Hospital
Southampton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

QR-010

Placebo

Arm Description

QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.

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

Outcomes

Primary Outcome Measures

Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study

Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)

Severity of Treatment Emergent Adverse Events From Baseline Through End of Study

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.

DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.

Secondary Outcome Measures

Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings.

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

Cmax: QR-010 maximum serum concentrations

Time to Maximum Serum Concentration

Tmax: Time to Cmax of QR-010 serum concentrations.

Terminal Half-life (T1/2)

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)]

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-∞)]

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)

CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.

Full Information

NCT ID

NCT02532764

First Posted

August 13, 2015

Last Updated

January 15, 2019

Sponsor

ProQR Therapeutics

Collaborators

European Commission

1. Study Identification

Unique Protocol Identification Number

NCT02532764

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

June 2015 (undefined)

Primary Completion Date

September 14, 2017 (Actual)

Study Completion Date

September 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ProQR Therapeutics

Collaborators

European Commission

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

cystic fibrosis, ΔF508, RNA therapies, antisense oligonucleotide, CFTR, F508del, CF, RNA therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

QR-010

Arm Type

Experimental

Arm Description

QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

QR-010

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Normal Saline

Primary Outcome Measure Information:

Title

Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study

Description

Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)

Time Frame