Source: http://www.allenovery.com/publications/en-gb/CRISPRsite/CRISPRintroduction/Pages/Clinical-trials.aspx
Timestamp: 2019-10-20 09:44:46
Document Index: 284956801

Matched Legal Cases: ['ART019', 'ART019', 'ART019', 'ART019', 'ART019', 'ART019', 'ART019']

Clinical trials - About CRISPR - Allen & Overy
In 2017, the University of Pennsylvania hopes to begin its ambitious CRISPR-related clinical trial (the first and currently only such trial to receive approval in the US) which aims to use CRISPR to perform three different genetic modifications on T-cells. The trial (in patients with myeloma, sarcoma or melanoma) aims not only to use CRISPR to disrupt PD-1 receptor expression, but also to knock out portions of the T-cell’s primary receptor. The reason for the latter is to maximise the effect of a further (non-CRISPR based) modification the researchers will make to the T-cells – introducing an engineered NS ESO-1 receptor to the T-cell. By knocking down/out the primary receptor, preventing PD-1 mediated T-cell deactivation and introducing this engineered new receptor, it is hoped that the T-cells will selectively hone in on NS-ESO-1 antigen displaying cancer cells.
Workflow for UPenn CRISPR trial to disrupt PD-1 protein, natural T cell receptor and introduce receptor specifically designed to target cancer.
The following clinical trials involving CRISPR are also currently taking place or are proposed to take place:
Information provided by clinicaltrials.gov:
1. A Safety and Efficacy Study of TALEN and CRISPR-Cas in the Treatment of HPV-related Cervical Intraepithelial Neoplasia (NCT03057912)
Collaborator: Jingchu University of Technology
Purpose: This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR-Cas to possibly treat HPV Persistency and human cervical intraepithelial neoplasia without invasion. The primary objective of this study is to evaluate the safety of therapeutic doses and the dosing regimen of TALEN and CRISPR-Cas plasmid.
Experimental: TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice a week for four weeks. CRISPR-Cas (CRISPR-Cas-HPV16 E6/E7T1 or CRISPR-Cas-HPV18 E6/E7T2) plasmid in gel, administered twice a week for four weeks.
Estimated Enrolment: 60
Anticipated Study Start Date: 15 July 2017
Estimated Study Completion Date: 15 July 2018
Estimated Primary Completion Date: 15 April 2018
2. Safety of Transplantation of CRISPR CCR5 Modified CD34+ Cells in HIV-infected Subjects with Hematological Malignances (NCT03164135)
Collaborators: Peking University, Capital Medical University
Purpose: The investigators performed this study to evaluate the safety and feasibility of transplantation with CRISPR-Cas CCR5 gene-modified CD34+ hematopoietic stem/progenitor cells for patients that develop AIDS and haematological malignancies. Patients will be treated with antiviral therapy (ART) to achieve undetectable HIV-1 virus in peripheral blood before conditioning. CD34+ cells from donors will be infused into the patients after treatment with CRISPR-Cas to ablate CCR5 gene.
Experimental: Participants will be transplanted with CD34+ cells which are treated using the CRISPR-Cas system to disrupt CCR5 gene. The persistence of CCR5 gene disruption in engrafted cells will be evaluated by sequencing.
Estimated Enrolment: 5
Anticipated Study Start Date: 30 May 2017
Estimated Study Completion Date: 20 May 2021
Estimated Primary Completion Date: 20 May 2019
3. Examining the Knowledge, Attitudes, and Beliefs of Sickle Cell Disease Patients, Parents of Patients with Sickle Cell Disease, and Providers Towards the Integration of CRISPR in Clinical Care (NCT03167450)
Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC), National Human Genome Research Institute (NHGRI)
Purpose: To study the attitudes, beliefs and opinions of those with SCD, parents of those with SCD, and providers on the use of CRISPR-Cas gene-editing. An additional purpose of this study is to assess the utility of an educational tool for improving understanding of CRISPR-Cas.
Estimated Enrolment: 90
Anticipated Study Start Date: 1 June 2017
Estimated Study Completion Date: 30 June 2018
Estimated Primary Completion Date: 30 June 2018
4. Identification of Host Factors of Norovirus Infections in Mini-Gut Model
Information provided by (responsible party): CHAN CHI WAI, Chinese University of Hong Kong.
Purpose: The primary objective in this study is to establish a list of host cellular proteins that mediate norovirus infection.
Experimental: In this study, intestinal stem cells will be isolated from duodenal biopsies collected from participants, followed by differentiation into mini-guts. Genome-wide genetic screening for host essential and restrictive factors will be performed on infected mini-guts by knockout CRISPR and gain-of-function CRISPR SAM, respectively. Shortlisted candidates will undergo preliminary functional validation in cell lines. These data will provide insights into potential therapeutic targets against norovirus infection.
5. A Study Evaluating UCART019 in Patients with Relapsed or Refractory CD19+ Leukemia and Lymphoma (NCT03166878)
This study is currently recruiting for participants
Information provided by (Responsible Party): Weidong Han, Chinese PLA General Hospital
Purpose: The main goal of the phase 1 portion of this phase 1/2 trial is to evaluate the safety and tolerability of several doses of UCART019 in patients with relapsed or refractory CD19+ leukemia and lymphoma, so as to establish the recommended dose and/or schedule of UCART019 for the phase 2 portion. The recommended Phase 2 dose will be defined as the highest dose level of UCART019 that induced DLT in fewer than 33% of patients (i.e. one dose level below that which induced DLT in at least two of six patients). The phase 2 portion of the trial will not be initiated until the recommended Phase 2 dose is determined. In the phase 2 portion of this trial, we will mainly determine if UCART019 help the body’s immune system eliminate malignant B-cells. Safety of UCART019 and the impact of this treatment on survival will also be observed.
Experimental: Gene-disrupted allogeneic CD19-directed BBζ CAR-T cells (termed UCART019) have been generated by combining the lentiviral delivery of CAR and CRISPR RNA electroporation to disrupt endogenous TCR and B2M genes simultaneously. This study will test whether it can evade host-mediated immunity and deliver anti-leukemic effects without graft versus host disease (GvHD).
6. PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer (NCT03081715)
Sponsor: Hangzhou Cancer Hospital
Collaborator: Anhui Kedgene Biotechnology Co.,Ltd
Purpose: This study will evaluate the safety of PD-1 knockout engineered T cells in treating advanced esophageal cancer. Blood samples will also be collected for research purposes.
Experimental: Peripheral blood lymphocytes will be collected and programmed cell death protein 1 (PD-1) gene will be knocked out by CRISPR-Cas in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients.
Estimated Enrolment: 21
Anticipated Study Start Date: 20 March 2017
Estimated Study Completion Date: 30 December 2018
Estimated Primary Completion Date: 27 February 2018
7. Stem Cells in NF1 Patients with Tumors of the Central Nervous System
Information provided by (Responsible Party): Roger Packer, Children’s Research Institute
Purpose: This study seeks to develop stem cells lines in children with NF1-related tumors in the central nervous system (the optic nerve and those from other brain sites). Stem cells from these subjects will provide a critical insight into the mechanisms responsible for tumor progression and symptoms associated with the central nervous system, accelerating the identification of therapeutic targets.
3.1 Study Design Cross-sectional collection of NF1 subjects with tumors in the central nervous system as documented by MRI.
3.2 Study Visits Subjects will have only one visit to collect the blood sample.
3.3 Study Procedures
3.31 Blood Draw – Subjects have 20 ml of whole blood drawn during either (1) their sedation for their clinically indicated MRI (IV already being placed for clinical purpose) or (2) through the outpatient laboratory.
3.32 Stem Cell Processing – Blood collected will be immediately transferred to the stem cell facility at the National Institutes of Health for processing of the specimens in order to develop stem cell lines.
3.33 Demographics – We will collect the subject’s age, gender, race, ethnicity, location of tumours in the central nervous system on MRI, history of vision loss and other neurological deficits.
3.34 Statistical Analysis – As a first step to establish a stem cell library from a specific population of NF1 children with nervous system tumours, we will not need statistical analysis at this stage.
Estimated Enrolment: 20 participants
Study start date: 27 November 2015
Estimated Study Completion Date: 1 June 2019
Estimated Primary Completion Date: 1 June 2019
8. PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer (NCT02863913)
Collaborator: Cell Biotech Co., Ltd.
Purpose: This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced bladder cancer. Blood samples will also be collected for research purposes.
Experimental: Peripheral blood lymphocytes will be collected and the programmed cell death protein 1 (PDCD1) gene will be knocked out by CRISPR-Cas in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients.
9. PD-1 Knockout Engineered T Cells for Castration‑resistant Prostate Cancer (NCT02867345)
Purpose: This study will evaluate the safety of PD-1 knockout engineered T cells in treating castration‑resistant prostate cancer (CRPC). Blood samples will also be collected for research purposes.
10. PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma (NCT02867332)
Purpose: This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced renal cancer. Blood samples will also be collected for research purposes.
Experimental: Peripheral blood lymphocytes will be collected and programmed cell death protein 1 (PDCD1) gene will be knocked out by CRISPR-Cas in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients.
11. PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer (NCT02793856)
Collaborator: Chengdu MedGenCell, Co., Ltd.
Purpose: This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic non‑small cell lung cancer. Blood samples will also be collected for research purposes.
Estimated Enrolment: 15
12. PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies (NCT03044743)
Sponsor: Yang Yang
Information provided by (Responsible Party): Yang Yang, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Purpose: This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes.
Experimental: Peripheral blood lymphocytes will be collected and the programmed cell death protein 1 (PDCD1) gene will be knocked out by CRISPR-Cas system and EBV-CTL will be generated in the laboratory (PD-1 Knockout EBV-CTL).
Actual Study Start Date: 7 April 2017
1 PD-1 is a “checkpoint” molecule which is present on the surface of many cancer cells and, when bound to PD-1 receptors on the surface of T-cells, disables the T-cell function. Monoclonal antibodies such as Merck’s Keytruda, which target the PD-1 receptor, have proven effective against various cancers.