PROPOSAL Early Phase Clinical Trials 2015

Transcription

1 PROPOSAL Early Phase Clinical Trials 2015 DEADLINE: Tuesday, January 12 th, 2016, 2:00 p.m. EST Award announcements will be made in February This Proposal is an example only. Do not complete this paper application. Please submit the Proposal online through the Institute s grant management system at Application Number: Project Title: Applicant Details Team Members Organizations Primary Contact Information 1. Salutation: Primary Address: Organization: Role in Project Principal Applicant Estimated Time Spent on Project % First Name: Position Title: Phone: Co-Applicant Last Name: Other Affiliations/ Position Titles: Collaborator 2. Salutation: Primary Organization: Address: Principal Applicant % First Name: Position Title: Phone: Co-Applicant Last Name: Other Affiliations/ Position Titles: Collaborator Note: Projects are not limited to two team members as laid out on this sample application form; projects may include as many team members as needed for the successful execution of the project. A Curriculum vita (NIH biosketch or equivalent) of five pages or less is required for each team member. Application Number: 1 of 17

2 Application Overview Keywords to describe the proposed work: What type of therapeutic(s) is/are being developed as the main goal of the project? (please select all that apply) Biologic Cell therapy Electrical brain stimulation Magnetic brain stimulation Medical device Small molecule Surgical intervention Active immunotherapy Passive immunotherapy Other Please specify: What clinical trial phase(s) of development does the project cover? Please explain your choice in 1-2 sentences. (please select all that apply) Phase I Phase IIa Other Please specify: Explanation: Research will have a significant impact in which neurodegenerative disease(s) of aging? (Please select all that apply. There is no benefit to selecting more diseases than fewer diseases.) Alzheimer s disease Amyotrophic lateral sclerosis Dementia with Lewy bodies Frontotemporal dementia Multiple system atrophy Parkinson s disease Progressive supranuclear palsy Mild cognitive impairment as prodromal to one of the other listed diseases Have you applied to other funding agencies with the same proposed work? (This information will not be used to assess the application) Yes Please specify: No Application Number: 2 of 17

3 Is this your first time applying for a neuroscience grant from the Institute? (This information will not be used to assess the application) Yes No Is this your first application for a research grant specifically in the area of neurodegenerative diseases of aging? (This information will not be used to assess the application) Yes No Other funding support: What percent of the proposed work is being funded by other grants (0-100%)? Location of work: what proportion of the proposed work is being carried out outside of Canada? If any, please explain how this will bring unique resources into Canadian-led work. Application Number: 3 of 17

4 Project Information 1. Abstract: Please summarize your proposed early phase clinical trial. (maximum 250 words) 2. Goals and specific aims: (maximum 500 words) 3. Experimental approach 3.1. Experimental design: Please include details of the trial design and methods, such as: a) the length of the trial (including regulatory and REB milestones); b) rationale for all primary and secondary outcome measures/endpoints c) rationale for the use of certain tools, techniques, or protocols (e.g. PET imaging, biomarker analysis, cognitive tests); d) the target population, and the inclusion/exclusion criteria, e) justification for the proposed dosage, formulation, frequency and route of administration. If there is no sufficient evidence for a particular dose, please explain how the current study will determine the optimal dosage. (maximum 2700 words) 3.2 Description of the power analysis: Please include detailed power calculations that provide justification for the number of subjects in each condition (ie. adequacy of the sample size for statistical analysis of the proposed study). Calculations should also include details on effect size, simulation software, the source of parameter estimates and the primary analytic technique (e.g., t-test used or a mixed model repeated measures analysis?). (maximum 250 words) 3.3 Rationale for testing in humans: Please provide the rationale for testing this therapeutic or intervention in humans including: a) preclinical efficacy, PK/PD, and results from IND-enabling studies (if available); b) any known mechanisms of action; c) toxicity, adverse events, safety concerns, and contraindications; d) If this trial proposes a repurposing/repositioning of the therapeutic or intervention, please provide the relevant results from other indications. (maximum 1500 words) Note: PK/PD data can be uploaded as a PDF to a maximum of 1 page under the Supplementary Materials section Plan for acquiring the study therapeutic: Please describe the plan for obtaining the therapeutic (small molecule, biologic, device, equipment and control, as applicable) including any cross-border or intellectual property considerations. (maximum 250 words) Application Number: 4 of 17

5 3.5 Recruitment plan: Please describe the plan for recruiting subjects. a) sources of patients, b) approach to attracting and retaining subjects, c) justification for the number of clinical sites used, d) justification for any assumptions made to estimate the rate of recruitment, e) expected drop-out rate, f) contingency plans and a list of anticipated challenges. (maximum 500 words) 3.6. DSMB: Please provide information on the composition, roles, schedule of meetings, and reporting activities of the DSMB. The DSMB should be composed of at least 3 and no more than 7 members (typically an odd number for voting purposes) who are independent of running the trial, and are free of conflicts of interest with the co-applicants. (maximum 250 words) 4. Limitations of the proposal: What do you consider to be the limitations of this proposal (this refers to the proposal overall and is not limited to the experimental approach)? (maximum 250 words) 5. Development plan: What is your administrative and experimental plan for advancing this line of inquiry (e.g. if current trial is successful, how will larger trials be funded, in which countries can commercialization of the drug be pursued)? (maximum 250 words) 6. Team and environment: please describe the roles of the principal applicant and co-applicants regarding governance, biostatistical analysis, data management, study sponsoring, administrative oversight, data safety monitoring and advisory committee, as applicable. How are the investigator(s), environment and collaborations (if applicable) particularly suited to achieve the aims of the proposed work? Does any team member have previous experience with clinical trials of similar complexity? (maximum 250 words) List of publications cited in the application and other publications directly relevant to the proposed work: Please include full citations and PMID. Application Number: 5 of 17

6 Small Molecule Profile Applications proposing a small molecule as a potential must complete this section for the proposed small molecule. Please fill in all known information pertaining to the indication and dosing that you are pursuing, except where noted. Small Molecule Profile Acronym Legend: BID IND IV MTD QD two times per day investigational new drug intravenous maximum tolerated dosage four times per day PD PK SC TID pharmacodynamics pharmacokinetics subcutaneous three times per day What stage(s) of development have been completed for the small molecule? (please select all that apply) Animal Model: Efficacy studies PK/PD Toxicity studies Safety studies Humans: Clinical Phase I Clinical Phase IIa Clinical Phase IIb Clinical Phase III Other Model Please specify which models: Efficacy studies PK/PD Toxicity studies Safety studies Drug-target relationship Selectivity Untested/unknown Non-selective; hits many targets Non-selective; hits within a general class of targets Selective for targets family/isoforms Selective for target In vitro potency Untested/unknown Micromolar Please specify: Nanomolar Please specify: Cellular potency Untested/unknown Micromolar Please specify: Nanomolar Please specify: Application Number: 6 of 17

7 Efficacy in preclinical models Is there a PK/PD relationship? Not done yet Yes No What is the BBB bioavailability of the small molecule? Has efficacy been tested in models? Not tested Tested Please specify which models: What is the BBB penetrability in the target region (as a % of serum exposure)? Clinical experience with the small molecule (please select all that apply) Pharmacodynamic outcome Unknown/untested Not possible to determine Suggested by the PK Tested Phase I: Have you tested dose ranges? Not tested Currently being tested Completed Please specify dose ranges: Phase I: Safety and tolerability MTD identified Please describe: MTD not yet identified - further studies Please describe: MTD not identified - no further study needed Please describe: Phase II: Dosing Untested/unknown IV dosing for efficacy studies SC dosing for efficacy studies BID/TID oral dosing for efficacy studies QD oral dosing for efficacy studies Phase II: Safety and tolerability Untested/unknown Dose limiting safety/tolerability identified Safety/tolerability of significant concern Safety/tolerability of minor concern Phase II: Efficacy Untested/unknown Not established Supports advancement to Phase III Please describe the relevant details of any other clinical trials done on the small molecule at other doses or for other indications, including where applicable the stage, indication, dosing regimen, route of administration, contraindications and brief results (including whether and where the small molecule has been given marketing approval by a regulatory body such as the FDA). Application Number: 7 of 17

8 Therapeutic Profile If you are not proposing a small molecule, do not fill out the Small Molecule Profile. Instead, provide any similar information needed to supplement the Project Information below. Application Number: 8 of 17

9 Budget Year 1 (please use this same form to complete the budgets for Years 2 to 4, if applicable) Personnel Costs Name Role in Project Estimated Time Spent on Project 1. % 2. % Laboratory Supplies Base Salary Salary Requested Benefits Requested Subtotal Description Unit Cost Number of Units Animal Costs Subtotal Description Unit Cost Number of Units Patient Care Costs Subtotal Description Unit Cost Number of Units Other Costs Subtotal Description Unit Cost Number of Units Subtotal Total Requested Budget Total Total Total Total Total Budget Justification: How do the budget items appropriately support the work proposed? Please note that: - Funds will be granted only for direct costs that are appropriate and justifiable for the work Application Number: 9 of 17

10 proposed. - Each item and its cost must be clearly described in the budget. - Funds cannot be used for equipment purchases, computer purchases, travel expenses to scientific conferences/meetings, administrative costs or indirect costs, unless prior written approval from the Institute has been obtained. - The grant amount may not be for the full amount requested. - Up to 35% of the funds can be used to bring unique international resources into Canadian-led work. Application Number: 10 of 17

11 Milestone Instructions Information Required Start-Up Funding Amount requested Payment Date Descriptions/Explanations If justified, a small amount of funding may be released to support initial milestones that must occur before work starts, such as hiring staff or obtaining research ethics board approvals. Milestones in this category must be completed before payment for the 1 st tranche of funding can be released and the project can begin. Date requested to receive payment relating to Start-Up Funding milestones. Format: e.g., February 17, 2015 Project Start and End date Format: e.g., April 17, 2015 Excludes Start-Up Funding Tranches Amount requested for each tranche Indicate the amount of grant funds required to complete listed milestones within each tranche. Funding requested between tranches should match the budget requested. Start and End Date for each tranche Milestones List milestones that will be completed within each tranche Indicate relevant aims for each milestone within each tranche under Project Aim Provide quantifiable milestones in each tranche If work is ongoing or covers multiple tranches (e.g., recruiting patients), please provide interim milestones for The Start Date is the date by which funding is expected to be released. Previous milestones (including Start-Up Funding milestones, if any) must be completed before the next tranche payment is released. Format: e.g., April 17, 2015 Milestones should be tailored to the project and work proposed, and designed so that whether or not they have been met can be clearly determined. See milestone template example on the next page. Examples: Recruitment of 20 patients; generation of animal colony of 50 mice; perform power analysis; hire 1 post-doctoral student to perform mouse behavioural testing Example: Recruiting 30 patients across 1 year for CSF collection can be divided into milestones as follows: Application Number: 11 of 17

12 each tranche. Include running totals. 1 st tranche CSF collected from 20 patients (running total: 20/30) 2 nd tranche CSF collected from 10 patients (running total: 30/30) Example: Start-Up Funding (optional) Description 1. Research ethics board approvals Amount: 5,000 Payment Date: June 01, st Tranche of Funding Amount: 50,000 October 01, 2015 March 31, 2016 Project List of milestones to be completed with the 1 st Tranche of funding Aim 1 Generation of 3xTg AD mice, N=50 (running total=50/100) 1 Generation of Control mice, N=50 (running total=50/100) 2 Complete setup of behavioural suite for object recognition test 2 nd Tranche of Funding Amount: 50,000 April 01, 2016 October 31, 2016 Project List of milestones to be completed with the 2 nd Tranche of funding Aim 1 Generation of an additional 3xTg AD mice, N=50 (running total=100/100) 1 Generation of an additional Control mice, N=50 (running total=100/100) 2 Perform object recognition test on 3xTg AD mice, N=25 (running total=25/100) 2 Perform object recognition test on 3xTg AD mice, N=25 (running total=25/100) 3 Measure tau phosphorylation levels from 3xTg AD mice brain soluble fractions following behavioural testing, N=25 (running total=25/100) 3 Measure tau phosphorylation levels from Control mice brain soluble fractions following behavioural testing, N=25 (running total=25/100) Application Number: 12 of 17

13 Milestones Please list key milestones for your project. Milestones will be used to help follow the progress of the proposed project. Funds will be disbursed in tranches, linked to the completion of these milestones. Funds should be disbursed in approximately 2 tranches per year (e.g., a total of 3 tranches for a 1.5 year grant); however, alternatives can be proposed (please describe why under Notes). Start-Up Funding (optional) Amount: Payment Date: Description Project Month, Day, Year Project Month, Day, Year 1 st Tranche of Funding Amount: Project Aim List of milestones to be completed with the 1 st Tranche of Funding 2 nd Tranche of Funding Amount: Project Aim List of milestones to be completed with the 2 nd Tranche of Funding 3 rd Tranche of Funding Amount: Project Aim List of milestones to be completed with the 3 rd Tranche of Funding 4 th Tranche of Funding Amount: Application Number: 13 of 17

14 Project Aim List of milestones to be completed with the 4 th Tranche of Funding 5 th Tranche of Funding Amount: Project Aim List of milestones to be completed with the 5 th Tranche of Funding 6 th Tranche of Funding Amount: Project Aim List of milestones to be completed with the 6 th Tranche of Funding 7 th Tranche of Funding Amount: Project Aim List of milestones to be completed with the 7 th Tranche of Funding 8 th Tranche of Funding Amount: Project Aim List of milestones to be completed with the 8 th Tranche of Funding (Include additional tranches of funding if needed, i.e., 9th Tranche of Funding, etc.) Additional milestone related information (if needed): Application Number: 14 of 17

15 Supplementary Materials (optional) You may submit supplementary materials to a maximum of 20 pages. The content included under Supplementary materials should be directly relevant to the proposed work or cited in the Proposal. Any materials beyond 20 pages, and/or that are not relevant will not be reviewed. Supplementary materials should not contain additional text for the application. Supplementary materials may include: Photographs, figures, tables cited in the Proposal Preliminary data Up to 1 manuscript relevant to the project Any patents (pending or granted) related to the project Application Number: 15 of 17

16 Principal Applicant/Institutional Signatures Please ensure the necessary parties sign this page. Per signatures cannot be accepted. Signatures can be submitted on separate pages. This Proposal may be executed by the parties in counterparts and may be delivered in electronic format, with all counterparts and electronic transmissions being as effective as a manually executed copy and together will constitute one and the same Proposal. I declare that to the best of my knowledge the statements and other information contained in this application are truthful, complete, and accurate. I further understand that an incomplete application will not be reviewed. Signature Print Name Date Official institutional signature of Principal Applicant s institution: Signature Print Name Date Application Number: 16 of 17

17 Co-Applicant/Collaborator Signatures Please have all co-applicants and collaborators sign this page. Per signatures cannot be accepted. Signatures can be submitted on separate pages. This Proposal may be executed by the parties in counterparts and may be delivered in electronic format, with all counterparts and electronic transmissions being as effective as a manually executed copy and together will constitute one and the same Proposal. I am aware that I am a collaborator on this grant and I declare that to the best of my knowledge the information contained in this application are truthful, complete, and accurate. Co-Applicant/Collaborator: Signature Print Name Date Co-Applicant/Collaborator: Signature Print Name Date Co-Applicant/Collaborator: Signature Print Name Date Co-Applicant/Collaborator: Signature Print Name Date Co-Applicant/Collaborator: Signature Print Name Date Application Number: 17 of 17