Clinical Trials

Date: 2016-10-27

Type of information: Results

phase: 1

Announcement: results

Company: ProQR Therapeutics (The Netherlands)

Product: QR-010

Action mechanism:

• oligonucleotide. QR-010 is a first-in-class RNA-based oligonucleotide designed to address the underlying cause of the disease by repairing the mRNA in CF patients that have the DF508 mutation. The DF508 mutation is a deletion of three of the coding base pairs, or nucleotides, in the CFTR gene, which results in the production of a misfolded CFTR protein that does not function normally. QR-010 is designed to bind to the defective CFTR mRNA and restore CFTR function.
• QR-010 is designed to be self-administered through a small, handheld aerosol delivery device, or nebulizer, in the form of a mist inhaled into the lungs. QR-010 has been granted orphan drug designation in the United States and the European Union. The QR-010 project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633545.
• Two global clinical trials for QR-010 in CF patients were started in 2015: a Phase 1b single-ascending dose (SAD) and multiple ascending dose (MAD) study in 64 patients (Study 001) and a proof of concept study in 16 CF patients (Study 002). Study 002 and the SAD portion of Study 001 were completed and data were presented during the North American CF Conference (NACFC) in October 2016.

Disease: cystic fibrosis

Therapeutic area: Rare diseases - Genetic diseases - Lung diseases

Country: Belgium, France, USA

Trial details:

• PQ-010-002 is a 28-day study conducted in up to 5 sites located in the US and Europe that are experienced in conducting nasal potential difference (NPD) measurements. NPD is a well-accepted diagnostic test for cystic fibrosis and recently has been used to assess therapeutic benefit in clinical trials of investigational agents. The study will enroll at least 16 people with CF that are either homozygous or compound heterozygous for the ?F508 mutation. NPD and sweat chloride measurements will be done before and after local treatment in the nose with QR-010 three times a week for four weeks. PQ-010-002 will be conducted in parallel with PQ-010-001, the ongoing Phase 1b safety and tolerability study of QR-010 in CF patients homozygous for the ?F508 mutation. In addition to safety and tolerability, PQ-010-001 will assess pharmacokinetics and exploratory clinical efficacy endpoints. In the Phase 1b study, QR-010 is delivered to the lungs via inhalation. (NCT02564354)

Latest news:

• • On October 27, 2016, ProQR Therapeutics announced that clinical study PQ-010-002, a proof-of-concept study of nasal potential difference (NPD), demonstrated that QR-010 restored CFTR function in a cohort of homozygous ?F508 cystic fibrosis (CF) patients. The study met its primary endpoint in this cohort as measured by a change in total chloride response following 4 weeks of treatment with QR-010. In the compound heterozygous ?F508 cohort, no meaningful difference was found. QR-010 was observed to be safe and well-tolerated in both cohorts. The top-line results of PQ-010-002 have been presented  by Noreen R. Henig M.D. and John P. Clancy M.D. at the North American Cystic Fibrosis Conference (NACFC) in Orlando.
• The study was conducted in 5 nasal potential difference (NPD) specialized centers in the US and Europe. The study enrolled 18 CF patients, 10 homozygous for the ?F508 mutation and 8 compound heterozygous (one copy of the ?F508 mutation and one copy of another cystic fibrosis disease-causing mutation). QR-010 was applied topically to the nasal mucosa 12 times over a period of 4 weeks. Primary endpoint for each cohort was the change from baseline in CFTR mediated total chloride transport as measured by NPD. In the per-protocol population of subjects homozygous for the ?F508 mutation meeting the pre-specified inclusion criteria (n=7), the average change from baseline in NPD at day 26 was statistically significant, -4.1 mV (p=0.0389). This finding was supported by a change in sodium channel activity and other sensitivity analyses of the NPD measurements, all pointing to strong evidence of restoration of CFTR activity. In subjects compound heterozygous for the ?F508 mutation, the average change from baseline in NPD was not significantly different at day 26. A responder analysis of individual subjects assessing the impact of the second mutation is currently ongoing.
• • On June 21, 2016, ProQR Therapeutics announced that topline data from study PQ-010-002, a proof-of-concept study to evaluate the effect of QR-010 on nasal potential difference (NPD) will be released at the North American Cystic Fibrosis Conference (NACFC) held on October 27 - 29, 2016 in Orlando, Florida.
• • On September 14, 2015, ProQR Therapeutics announced that PQ-010-002 is open for enrollment. The primary objective of PQ-010-002 is to estimate the effect of topical administration of QR-010 on the nasal mucosa in the restoration of CFTR function, as measured by Nasal Potential Difference (NPD). PQ-010-002 is an open-label, exploratory study evaluating the effect of QR-010 in ?F508 homozygous (carry two allelic copies) and compound heterozygous (carry one copy of the ?F508 mutation and one other disease causing mutation) cystic fibrosis (CF) patients. QR-010 is a novel investigational RNA therapeutic designed to repair the genetic mutation in the mRNA of CF patients due to the ?F508 mutation.

Is general: Yes