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QR-010

Phase 1

Cystic Fibrosis | Small molecule | Respiratory |ProQR Therapeutics N.V.|Last Updated: Sep 24, 2020

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment88
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02564354Exploratory Study to Evaluate QR-010 in Subjects With Cystic Fibrosis ΔF508 CFTR MutationPHASE1 COMPLETED 18Sep 1, 2015Sep 1, 2016Sep 24, 20205 United States, Belgium +1
NCT02532764Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis PatientsPHASE1 COMPLETED 70Jun 1, 2015Sep 14, 2017Feb 6, 201927 United States, Belgium +8
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Study Endpoints
Primary Endpoints
Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.

The primary endpoint was the within-subject change from baseline in total chloride transport as measured by NPD, after the Chloride-free+isoproterenol solution (Cl-free+iso), and was based on the average measurements of both nostrils. To provide baseline stability, baseline was defined as the average of the two most recent pre-dose values, where each pre-dose value was the average of two nostrils. A negative change from baseline of Cl-free+iso shows an improvement.

Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study
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
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.
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 Endpoints
Number of Subjects With a -6.6 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study.
2 and 4 weeks, and at 3 weeks post-treatment.
Number of Subjects With a -4 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study.
2 and 4 weeks, and at 3 weeks post-treatment.
Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study.
Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
ΔF508 HomozygousEXPERIMENTALQR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
ΔF508 Compound HeterozygousEXPERIMENTALQR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
QR-010EXPERIMENTALQR-010 administered via inhalation either as a single dose or three times weekly for four weeks.
PlaceboPLACEBO_COMPARATORPlacebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks.
Interventions
NameTypeDescription
QR-010DRUGSingle-stranded RNA antisense oligonucleotide in isoosmolar solution
PlaceboDRUGNormal Saline
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites5

Inclusion Criteria: * Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of \> 60 mmol/L * Nasal potential difference (NPD) measurement at Screening consistent with CF * Confirmation of CFTR gene mutations homozygous or compound heterozygous for t...

Countries:United StatesBelgiumFranceCanadaCzechiaDenmarkGermanyItalySpainUnited Kingdom
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