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FBO DAILY - FEDBIZOPPS ISSUE OF JUNE 28, 2018 FBO #6061
SOURCES SOUGHT

B -- Design of a clinical trial protocol for phenserine tartrate for traumatic brain injury

Notice Date

6/26/2018
 

Notice Type

Sources Sought
 

NAICS

541690 — Other Scientific and Technical Consulting Services
 

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 4211, MSC 9559, Bethesda, Maryland, 20892-9559, United States
 

ZIP Code

20892-9559
 

Solicitation Number

NIHDA201800286
 

Archive Date

7/17/2018
 

Point of Contact

Jon J Gottschalk, Phone: 3014439456
 

E-Mail Address

jon.gottschalk@nih.gov
(jon.gottschalk@nih.gov)
 

Small Business Set-Aside

N/A
 

Description

SOURCES SOUGHT NOTICE 1.Solicitation Number: NIHDA201800286 2.Title: Design of a clinical trial protocol for phenserine tartrate for traumatic brain injury 3.NAICS Code- 541690 - Other Scientific and Technical Consulting Services This is a Sources Sought Notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small-disadvantaged business; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code may still submit a response to this notice. BACKGROUND There are no FDA approved drugs for the pharmacological treatment of traumatic brain injury (TBI), despite the fact that some 10 to 42 million people worldwide, including more than 1.7 million Americans, experience a TBI annually [1]. TBI is now outstripping many common diseases as a major cause of death and disability [2] (30.5%). Notably, there is increased mortality in the elderly and a worse functional outcome following lower initial injury severity [3]. Growing evidence indicates that TBI triggers a pathological cascade that leads to early dementia onset [4,5] and is one of the most powerful risk factors for the development of Alzheimer's disease and related disorders [6]. By far the majority of TBIs are mild to moderate in nature and account for 80-95% of cases, with severe TBI comprising the remainder. With increases in survival rate following initial injury, TBI can result in substantial and lifelong cognitive, physical, and behavioral impairments that require long-term access to health care and disability services [7]. TBI-associated brain damage can be classified into two major phases. First, an initial primary damage phase occurs at the moment of insult. This includes contusion and laceration, diffuse axonal injury and intracranial hemorrhage, causing instantaneous (necrotic) cell death. This period is followed by a longer secondary phase that encompasses cascades of biological processes initiated at the time of injury that may persist over much greater times consequent to ischemia, neuroinflammation, glutamate toxicity, astrocyte reactivity, axonal shearing and apoptosis [8-11]. Increasing evidence suggests that secondary brain injury may be reversible; depending on the biological cascades that drive the delayed secondary phase that occurs following TBI and how quickly and effectively these can be interrupted or mitigated. Preclinical studies of the NIA experimental drug phenserine tartrate (PhenT) in a well-characterized mild concussive model of TBI in mouse [12] indicate that PhenT can not only mitigate the short-term behavioural impairments induced by TBI, but importantly can block the gene pathways that lead to longer term neurodegenerative disorders, like AD. Notably, PhenT has a broad spectrum of pharmacological actions of potential value for treating TBI, that include lowering the synthesis of amyloid precursor protein (APP) and alpha-synuclein (α-syn), proteins of consequence in the pathology of AD and Parkinson's disease, respectively. In addition, PhenT possesses anti-inflammatory properties [13], also a phenomenon of significance in TBI [14], as well as an array of trophic and, importantly, anti-apoptotic actions [15]. The focus of this SOW is to (i) critically evaluate all preclinical PhenT data in relation to its actions on neuronal cell survival, to (ii) design and write of a clinical trial to specifically evaluate PhenT as a new treatment for mild to moderate human TBI. Importantly, this clinical trial must be designed to maximize the multiple pharmacological properties of PhenT to positively impact the biological cascades instigated by TBI. It has become increasingly clear that multiple processes combine together following an insult (whether an acute TBI or a chronic degenerative disorder such as in AD or PD) to induce the pre-programed cellular dysfunction and death of neurons. Clinical trials in TBI of experimental drugs that act via a single mechanism only, such as anti-inflammatory or Aβ lowering approaches, have failed to address the full range of pathologies that lead to neuronal loss and cognitive impairment. PhenT's unique activation of multiple pathways (including the augmentation of endogenous antioxidant, neurotrophic, neuroprotective, anti-inflammatory, pro-angiogenesis, APP/Aβ/α-syn-lowering as well as cholinergic and others, importantly anti-apoptotic pathways) is critical to provide mitigation to the multiple pathways that are triggered by TBI in human TBI, which undoubtedly vary between individuals depending on their environmental and genetic backgrounds and the type of TBI encountered. It is hence critical, that the design of the requested PhenT TBI trial be undertaken by an experienced clinical trial scientist that has a clinical pharmacology background and prior expertize/knowledge of the drug of interest, specifically PhenT. PROJECT SUMMARY The evaluation of preclinical studies of PhenT action to mitigate TBI and neuronal PPCD in animal models, and development of a proof-of-concept clinical trial design to evaluate PhenT in human traumatic brain injury - taking into account the pharmacokinetics and pharmacodynamics of the drug to optimize brain target engagement. MANDATORY REQUIREMENTS ESSENTIAL STUDY REQUIREMENT FROM CONTRACTOR (i)Extensive background in clinical trial design - and specifically small phase 2 efficacy studies focused on neurodegeneration. (ii)Contractor MUST previously have analyzed the factors that can result in the failure of neurological drugs in clinical trials - given that neurological clinical drug development has one of the highest rates in the clinical drug development field (so that actions to limit failure can be included within the clinical trial design) (iii)Contractor MUST have previously evaluated PhenT drug actions - to be sufficiently aware of these actions to allow appropriate outcome measures to be included in to the clinical trial design (iv)Contractor MUST have extensive background knowledge in FDA regulatory mechanisms and requirements (as all clinical protocols on experimental drugs must be evaluated and approved by the FDA) - i.e., the contractor must demonstrate that they have previously been involved in a successful interventional clinical trial for a neurodegenerative disorder. Independent support of these essential requirements is necessary (such as scientific publications and/or demonstration of past successful phase 2 clinical trials of experimental compounds in a neurodegenerative disease - such as AD). PROJECT REQUIREMENTS Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below: Preclinical evidence is consistent with PhenT providing protection of neurons against preprogrammed cell death (PPCD) following a TBI insult, in both healthy rodents and in transgenic rodents possessing pathologies present in human Alzheimer's disease. These studies are in weight-drop mouse models and anoxic stroke rat models, and include behavioral, gene array, immunohistochemical and biochemical (Western blot) results. They are supported by ongoing controlled cortical impact TBI studies in mice. The SOW includes A review of preclinical data relating to PhenT and its actions to inhibit PPCD (evaluating behavioral, gene array, immunohistochemical and biochemical data) - to address wther this data is supportive of clinical development of PhenT as a treatment strategy for mild to moderate human TBI. A review of early interventional clinical trial design for mild to moderate human TBI (specifically in relation to outcome measures - that could be evaluated for PhenT, and that tie in with/cross-validate its preclinical studies). A translation of these findings (1 and 2, above) into a clinical trial designed to provide statistically significant evidence in humans confirming preclinical findings and the efficacy of PhenT, if present, in mild to moderate TBI subjects. A proof-of-concept draft protocol that takes into account PhenT pharmacokinetic and pharmacodynamics features in less than 75 subjects. ANTICIPATED PERIOD OF PERFORMANCE The anticipated performance is for one 2-month base period of performance following contract award. OTHER IMPORTANT CONSIDERATIONS The Government is expected to use procedures in FAR PART 13. The North American Industry Classification System (NAICS) code is 541690 with a size standard of $15.0 million. CAPABILITY STATEMENT/INFORMATION SOUGHT Please provide a capability statement, this includes: •Provide evidence the respondent has performed services. •Provide evidence of similar previous contracts of research of the same magnitude. •Information regarding (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed project of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, and other related information. Please provide your DUNS number, organization name, address point of contact, and size and type of business (e.g., 8(a), HubZone, etc.,) pursuant to the applicable NAICS code and any other information that may be helpful. Respondents should provide responses accordingly: (1) submit information electronically by email. No mail, telephone or facsimile responses will be accepted; (2) format capability statements using Microsoft Word or Adobe PDF including attachments, resumes, charts, etc. Use single space, 12 font minimum and 8.5 x 11 size paper; (3) organize material in such a manner that clearly identifies and addresses capability requirements and provide an executive summary; (4) capability statement should not exceed two pages not including the cover page, executive summary, or references; (5) RESPONSES SHOULD BE RECEIVED NO LATER THAN 4:00 PM EASTERN TIME ON July 2, 2018; (6) include respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and email addresses; and (7) send responses to this notice via email to jon.gottschalk@nih.gov. DISCLAIMER AND IMPORTANT NOTES This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. CONFIDENTIALITY No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any nonproprietary technical information in any resultant solicitation(s).
 

Web Link

FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIDA-01/NIHDA201800286/listing.html)
 

Place of Performance

Address: 251 Bayview Blvd, Baltimore, Maryland, 21224, United States

Zip Code: 21224
 

Record

SN04969175-W 20180628/180626231104-e107a9bd2f16e1a61bf44f682cb211ff (fbodaily.com)
 

Source

FedBizOpps Link to This Notice
(may not be valid after Archive Date)

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