A randomised, double-blind, placebo-controlled crossover study to assess the efficacy of a single dose of 100mg of VRP700 by inhalation in reducing the frequency and severity of cough in adult patients with Idiopathic Pulmonary Fibrosis - EPOCh

开始日期2013-03-25

申办/合作机构

Verona Pharma Plc

100 项与 VRP-700 相关的临床结果

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100 项与 VRP-700 相关的转化医学

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100 项与 VRP-700 相关的专利（医药）

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项与 VRP-700 相关的文献（医药）

2019-05-01·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Vaccine-Induced Memory CD8+ T Cells Provide Clinical Benefit in HER2 Expressing Breast Cancer: A Mouse to Human Translational Study

1区 · 医学

Article

作者: Morse, Michael A. ; Rogatko, Andre ; Lyerly, H. Kim ; Gwin, William ; Maecker, Holden T. ; Blackwell, Kimberly ; Hobeika, Amy C. ; Lubkov, Veronica ; Crosby, Erika J. ; Chang, Serena ; Kim, Sungjin ; Snyder, Joshua C. ; Hyslop, Terry ; Marcom, Paul K. ; Osada, Takuya ; Hartman, Zachary C. ; Broadwater, Gloria

Abstract:

Purpose::

Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T-cell infiltration of tumors include vaccines targeting established oncogenic drivers such as the genomic amplification of HER2. We constructed a vaccine based on a novel alphaviral vector encoding a portion of HER2 (VRP-HER2).

Patients and Methods::

In preclinical studies, mice were immunized with VRP-HER2 before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and antitumor function were evaluated. We tested VRP-HER2 in a phase I clinical trial where subjects with advanced HER2-overexpressing malignancies in cohort 1 received VRP-HER2 every 2 weeks for a total of 3 doses. In cohort 2, subjects received the same schedule concurrently with a HER2-targeted therapy.

Results::

Vaccination in preclinical models with VRP-HER2 induced HER2-specific T cells and antibodies while inhibiting tumor growth. VRP-HER2 was well tolerated in patients and vaccination induced HER2-specific T cells and antibodies. Although a phase I study, there was 1 partial response and 2 patients with continued stable disease. Median OS was 50.2 months in cohort 1 (n = 4) and 32.7 months in cohort 2 (n = 18). Perforin expression by memory CD8 T cells post-vaccination significantly correlated with improved PFS.

Conclusions::

VRP-HER2 increased HER2-specific memory CD8 T cells and had antitumor effects in preclinical and clinical studies. The expansion of HER2-specific memory CD8 T cells in vaccinated patients was significantly correlated with increased PFS. Subsequent studies will seek to enhance T-cell activity by combining with anti-PD-1.

2016-10-01·Pulmonary pharmacology & therapeutics3区 · 医学

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study

3区 · 医学

Article

作者: Lavorini, Federico ; Franciosi, Lui ; Page, Clive P ; Fontana, Giovanni A ; Walker, Michael J ; Spina, Domenico

BACKGROUND:

Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine.

OBJECTIVE:

To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP.

METHODS:

Eight female patients (mean age 71 years) with IIP were investigated in a double blind, randomised, placebo controlled crossover, adaptive contingency study design (EudraCT Number 2010-021350-19). The study consisted of a screening visit to assess the eligibility of patients, and two separated (48-72 h) study days. On the two study days, patients were randomised to receive either nebulized VRP700 (1.0 mg/kg) on the first study visit followed by nebulised placebo (sodium chloride 0.9%) on the second visit, or placebo on the first visit followed by VRP700 on the second visit. The primary endpoint was cough frequency over a 4-h assessment period; secondary endpoints were subjective cough-related level of discomfort as assessed by a visual analogue scale (VAS) and the subjective response to treatment as assessed by a quality of life question. Safety (ECG, spirometry, urine and blood tests) and adverse events occurring during the trial were also investigated.

RESULTS:

In all patients both VRP700 and placebo decreased cough frequency; however, mean decreases in cough frequency after treatment with VRP700 were significantly (P < 0.001) higher than with placebo. Similarly, mean reductions in VAS score were significantly (P < 0.001) higher after treatment with VRP 700 compared with placebo. All but one patient indicated that they felt better after receiving VRP700. No adverse events were reported during the study, nor were any changes in ECG variables, spirometry, urine and blood tests noted.

CONCLUSION:

The results of this exploratory study indicate that nebulised VRP700 improved cough and quality of life in hospitalised IIP patients with no significant side effects. A larger trial is warranted to assess these promising results.

项与 VRP-700 相关的新闻（医药）

2014-03-07

·BioSpace

Verona Pharma: - £13 Million Equity Issue, £1 Million Open Offer And Notice Of GM

6 March 2014, London – Verona Pharma plc (AIM: VRP), the drug development company focused on “first-in-class” medicines to treat respiratory diseases, announces a Placing, Subscription and Open Offer of up to 637,324,831 New Ordinary Shares at 2.2 pence each to raise up to £14.0 million before expenses. The Placing involves the issue of 298,750,000 New Ordinary Shares on a non-pre-emptive basis to raise gross proceeds of approximately £6.6 million. The Placing is not conditional upon the Open Offer being fully subscribed and the Placing Shares are not subject to clawback. The Subscription involves the issue of 292,000,000 New Ordinary Shares on a non-pre-emptive basis to raise gross proceeds of approximately £6.4 million. The Subscription is not conditional upon the Open Offer being fully subscribed and the Subscription Shares are not subject to clawback. In order to provide Shareholders who have not taken part in the Placing with an opportunity to participate in an issue of New Ordinary Shares at the Issue Price, the Company is making the Open Offer to provide all Qualifying Shareholders with the opportunity to subscribe at the Issue Price of 2.2 pence for an aggregate of up to 46,574,831 New Ordinary Shares, to raise gross proceeds of up to approximately £1.0 million. The Issue Price is at a discount of 36.4 per cent to the closing middle market price of 3.45 pence per Existing Ordinary Share on 5 March 2014. The Placing, Subscription and Open Offer are conditional, amongst other things, on the passing of the Resolutions by Shareholders at the General Meeting, which is to be held at the offices of SGH Martineau LLP at One America Square, Crosswall, London EC3N 2SG at 11.00 am on 24 March 2014. If the Resolutions are passed, the New Ordinary Shares will be allotted after the General Meeting. Admission is expected to occur no later than 8.00 a.m. on 25 March 2014 or such later time and/or date(s) as WH Ireland, WG Partners and the Company may agree. Neither the Placing nor the Open Offer is underwritten. Proposed use of proceeds The Company will use the proceeds of the Fund Raising in part to further the development of RPL554, a novel compound to initially address severe COPD. Three clinical trials will be performed using a nebulised formulation. These studies will guide the selection of an active dose and provide insight as to the therapeutic index. In addition, further pre-clinical studies will be undertaken to continue to prepare RPL554 for larger Phase 2b studies in hospitalised COPD patients. It is expected that the key data from these activities will be reported during 2015. The proceeds will also be used in part for additional pre-clinical work to prepare VRP700 for the next series of clinical studies in patients with chronic severe cough. In addition, the Company will conduct a dose-finding study with VRP700 to investigate the relationship between dose and effect in patients. It is anticipated that data from this study will be reported in the second half of 2015. Copies of the Circular will be posted to Verona Pharma Shareholders today. The Circular is also available for download on the Company's website: Dr. Jan-Anders Karlsson, CEO of Verona Pharma said: “I am delighted at the strong demand for shares from institutions in both the UK and US for this proposed fundraising, which was significantly oversubscribed. We intend to progress our lead pipeline asset, RPL554 in further Phase 2 studies, as soon as possible, through the next significant value inflection point. We believe this novel bronchodilator and anti-inflammatory drug has the potential to be an important new option for the treatment of acute COPD, our initial target indication, where currently used treatments are not sufficiently effective. We also believe that RPL554 could be used as a maintenance treatment in patients with moderate to severe forms of the disease. The funds raised will also be used to add significant value to VRP700 by performing pre-clinical work and further important Phase 2 clinical studies in patients with intractable cough. Additionally, we continue to expect data from a proof of principle clinical trial with VRP700 in patients with chronic cough in mid-2014.” “We would like to thank our existing investors for their continuing support and look forward to welcoming our new shareholders to the Company. We are confident that the progress we will make in the medium and longer term will not only result in important new medicines for patients with respiratory disease but will also translate into the creation of significant value for our shareholders.” Help employers find you! Check out all the jobs and post your resume.

First in Class

100 项与 VRP-700 相关的药物交易

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