DoD Amyotrophic Lateral Sclerosis, Pilot Clinical Trial Award

Description

The FY22 ALSRP Pilot Clinical Trial Award supports the rapid implementation of clinical trials with the potential to have a significant impact on the treatment or management of ALS. Projects may range from phase 1 to small-scale phase 2 trials and should aim to de-risk and inform the design of more advanced trials by investigating safety, feasibility, biomarker application, and therapeutic efficacy in relevant patient populations. Clinical trials may be designed to evaluate promising drugs, biologics, or devices with anticipated therapeutic impact that is supported by strong scientific rationale and existing preclinical data. Potential impact is not whether a therapy is ready at the conclusion of the trial, but rather if the outcomes will improve and accelerate future larger trials. Applications submitted to this award can have outcomes that focus on specific subpopulations of ALS patients or potentially even individual patients.Applicants not investigating a therapeutic, but proposing a clinical trial to optimize established ALS clinical care, must submit under a lower total direct cost Clinical Care Tier. Types of efforts that will be supported under this tier include but are not limited to optimization of respiratory care strategies, improvements to approved devices and assistive technologies, and/or specific symptom management strategies. The capacity for near-term impact on patient care is an important component of the Clinical Care Tier.Funding from this award mechanism must support a clinical trial. A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. For more information, a Human Subject Resource Document is provided at https://cdmrp.army.mil/pubs/pdf/Human%20Subjects%20Resource%20Document.pdf. Principal Investigators (PIs) seeking funding for a preclinical research project should consider one of the other FY22 ALSRP program announcements being offered. For information about these award mechanisms, see https://cdmrp.army.mil/funding/alsrpThe requested budget for the clinical trial must be justified and appropriate to the scope proposed. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.Funding for therapeutics must include plans to generate compelling biomarker data. Predictive, prognostic, and pharmacodynamic biomarkers are critical to improving trial design, patient selection, efficiency, and interpretation. Applicants must clearly describe a biomarker-driven approach and its potential to de-risk and improve the design of anticipated later-stage trials. For further description, see Attachment 13: Biomarker Statement. Biomarker development and characterization can include target engagement biomarkers, pharmacodynamic biomarkers to measure the biological effect of an investigational therapeutic, and/or predictive/cohort-selective biomarkers that indicate whether a specific therapy will be effective in an individual patient or patient subgroup.For further information on early-phase clinical trial design and biomarker types, qualifications, and their use in ALS clinical trials, it is recommended that applicants consult the following resources:• U.S. Food and Drug Administration (FDA) Guidance Document – “Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry.” September 2019. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry• Verber NS, Shepheard SR, Sassani M, et al. 2019. Biomarkers in motor neuron disease: A state of the art review. Frontiers in Neurology (10):291 https://www.frontiersin.org/articles/10.3389/fneur.2019.00291/full• van den Berg LH, Sorenson E, Gronseth G, et al. 2019. Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials. Neurology 92(14):e1610-e1623 https://n.neurology.org/content/92/14/e1610• Benatar M, Boylan K, Jeromin A, et al. 2016. ALS biomarkers for therapy development: State of the field and future directions. Muscle Nerve 53(2):169-182 https://doi.org/10.1002/mus.24979• FDA Biomarker Qualification Program, https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-programKey aspects of the Pilot Clinical Trial Award Mechanism:• Clinical Trial Start Date: The proposed clinical trial is expected to begin no later than 12 months after the award date or 18 months after the award date for FDA-regulated studies.• Preliminary Data are Required: Inclusion of preliminary data relevant to the proposed clinical trial is required.Study Population: The application should demonstrate the availability of and access to a suitable patient population that will support a meaningful outcome for the study. The application should include a discussion of how accrual goals will be achieved, as well as the strategy for inclusion of women and minorities in the clinical trial appropriate to the objectives of the study.• Intervention Availability: The application should demonstrate the documented availability of and access to the drug/compound, device, and/or other materials needed, as appropriate, for the proposed duration of the study.• Personnel and Environment: The application should demonstrate the study team’s expertise and experience in all aspects of conducting clinical trials, including appropriate statistical analysis, knowledge of FDA processes (if applicable), and data management. The application should include a study coordinator(s) who will guide the clinical protocol through the local Institutional Review Board (IRB) of record and other federal agency regulatory approval processes, coordinate activities from all sites participating in the trial, and coordinate participant accrual. The application should show strong institutional support and, if applicable, a commitment to serve as the FDA regulatory sponsor, ensuring all sponsor responsibilities described in the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312), Subpart D, are fulfilled.• Statistical Analysis and Data Management Plans: The application should include a clearly articulated statistical analysis plan, a power analysis reflecting sample size projections that will answer the objectives of the study, and a data management plan and use of an appropriate database to safeguard and maintain the integrity of the data. If FDA-regulated, the trial must use a 21 CFR 11-compliant database and appropriate data standards. For more on data standards, see https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/ FormsSubmissionRequirements/ElectronicSubmissions/UCM511237.pdf• Impact: Therapeutic outcomes should directly and substantially de-risk and inform the design of anticipated later-phase trials of the intervention under investigation. Optimization of current care should have near-term impact on patients. All interventions must offer significant potential impact for individuals affected by ALS, including specific subpopulations or potentially even individual patients.• Rationale: Both the anticipated therapeutic impact of the intervention and the proposed clinical trial outcomes must be supported by strong scientific rationale that is established through critical review and analysis of the relevant literature and preliminary data.• Trial Design: The proposed clinical trial design should include clearly defined objectives and appropriate endpoints/outcome measures, and comply with current Good Clinical Practice (GCP) guidelines.Safety Management Plan: The application should include a clearly articulated safety management plan outlining how safety pharmacovigilance will be conducted, as applicable.• Clinical Monitoring Plan: The application should include a clearly articulated clinical monitoring plan outlining how the study will be monitored for GCP compliance.• Study Coordinator: The application should include a study coordinator(s) who will guide the clinical protocol through the local IRB of record and other federal agency regulatory approval processes, coordinate activities from all sites participating in the trial, and coordinate participant accrual.• FDA Experience: The application should detail the study team’s interactions to date with the FDA, including previous FDA submissions, if applicable.• Transition Plan: Applications should include a Transition Plan (including potential funding and resources) showing how the intervention will progress to the next clinical trial phase and/or optimize current standard of care after the successful completion of the FY22 ALSRP Pilot Clinical Trial Award.• Institutional Support: The application should clearly demonstrate strong institutional support and, if applicable, a commitment to serve as the FDA regulatory sponsor, ensuring all sponsor responsibilities described in 21 CFR 312, Subpart D, are fulfilled.• Informed Consent Form: Funded trials are required to post a copy of the informed consent form used to enroll subjects on a publicly available federal website in accordance with federal requirements described in 32 CFR 219.

Eligibility

Grants.gov lists this opportunity under eligibility category code 99. These codes correspond to applicant types (state/local government, tribal organization, nonprofit, educational institution, individual, small business, etc.) defined in Grants.gov's own eligibility reference. See the current Grants.gov eligibility categories or check the official listing below for this opportunity's exact eligibility statement.

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