REQUEST FOR INFORMATION

BIOMEDICAL ADVANCED RESEARCH AND DEVELOPMENT AUTHORITY/INFLUENZA AND EMERGING INFECTIOUS DISEASES DIVISION (BARDA/IEIDD)

TITLE:  REQUEST FOR INFORMATION (RFI) REGARDING A PHASE 2 PLATFORM CLINICAL TRIAL INVESTIGATING HOST-DIRECTED THERAPIES FOR ACUTE RESPIRATORY DISTRESS SYNDROME

RFI No:  HHS-22-BARDA-RFI-ARDS-001

REQUEST FOR INFORMATION

BIOMEDICAL ADVANCED RESEARCH AND DEVELOPMENT AUTHORITY/INFLUENZA AND EMERGING INFECTIOUS DISEASES DIVISION (BARDA/IEIDD)

TITLE:  REQUEST FOR INFORMATION (RFI) REGARDING A PHASE 2 PLATFORM CLINICAL TRIAL INVESTIGATING HOST-DIRECTED THERAPIES FOR ACUTE RESPIRATORY DISTRESS SYNDROME

RFI No:  HHS-22-BARDA-RFI-ARDS-001

1.0 Description

1.1 The Influenza and Emerging Infectious Diseases Division (IEIDD), in support of the Biomedical Advanced Research and Development Authority (BARDA), is seeking feedback and input on a phase 2 platform clinical trial investigating immunomodulators or other host-directed therapies for the treatment of hospitalized patients with acute respiratory distress syndrome (ARDS). The intent is to promote the evaluation of novel pathogen-agnostic host-directed therapies in biomarker-defined subsets of patients with ARDS that are likely to benefit most from a given candidate therapeutic.

1.2 THIS IS A REQUEST FOR INFORMATION (RFI) ONLY

IEIDD is issuing this RFI solely for information and planning purposes – it does NOT constitute a Request for Proposal (RFP), a promise to issue an RFP, or a commitment to issue any type of solicitation in the future. This RFI does not commit the United States Government (USG) to contract any supply or service whatsoever. At this time, IEIDD is not seeking development proposals and will not accept or review unsolicited proposals received.

The USG will not pay for any information or administrative costs incurred in response to this RFI. All costs associated with responding to this RFI will be solely at the interested party’s expense. Submission is voluntary and is not required to propose a subsequent solicitation on this topic (if any).

If IEIDD chooses to release a solicitation in the future, it will be synopsized on the System for Award Management (https://www.sam.gov/SAM/) website and the BARDA website at https://www.medicalcountermeasures.gov/. It is the responsibility of the potential respondents to monitor these sites for additional information pertaining to any potential requirement.

2.0 Background

Within the USG, the Department of Health and Human Services (HHS), the Administration for Strategic Preparedness and Response (ASPR), the Biomedical Advanced Research and Development Authority (BARDA) is tasked with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective medical countermeasures to treat the adverse health effects resulting from intentional exposure to chemical, biological, radiological, and nuclear (CBRN) threat agents, and natural exposure(s) to pandemic influenza and emerging infectious diseases.

Prevention of disease caused by seasonal and novel influenza strains of pandemic potential continues to be a public health challenge. Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury primarily caused by severe pneumonia and sepsis due to bacterial and viral infections (e.g., influenza virus), leading to a high morbidity and mortality rate. To date, no approved or licensed pharmacological therapies are available for ARDS. Pathogen-specific drugs (e.g., antibiotics and antivirals) so far have had limited success at improving clinical outcomes in patients with ARDS. Therefore, host-directed therapeutics targeting immune dysregulation or promoting tissue repair are considered the most promising approach to address the unmet clinical need for treating ARDS. Although previous clinical trials investigating immune modulators for ARDS treatment, unfortunately, showed intermediate or conflicting clinical efficacy results when using an all-comers design, promising patient subgroups were identified in a post hoc analysis. Indeed, ARDS subgroups have distinct clinical and biological characteristics associated with different clinical outcomes and treatment responses. Increasing evidence suggests the use of immune-related biomarkers to improve the identification of specific subsets of ARDS patients that may benefit from specific host-directed therapeutics.

Therefore, to evaluate novel host-directed therapeutics in patients with ARDS as well as identify the associated biomarkers to define ARDS subgroups for that specific therapeutic candidate, BARDA is interested in investing in a platform, randomized, placebo-controlled, multi-center phase 2 trial to evaluate the efficacy and safety of novel immunomodulators or other host-directed therapeutics in patients with ARDS. We will collect extensive biomarker data from baseline to end of hospitalization to demonstrate the specific mechanism(s) of the proposed candidate therapeutic in modulating the host immune response, the natural history of ARDS, and a potential trigger for treatment for specific therapeutic candidates. The results from this trial are not intended to be pivotal, but the generated biomarker data would better inform the phase 3 study design for implementing biomarker-based patient stratification to increase the likelihood of achieving clinical efficacy of a specific drug in a targeted subgroup of ARDS patients.

3.0 Requested Information

This RFI seeks feedback and additional input from organizations and pharmaceutical companies on the Draft Protocol Synopsis for a randomized, double-blind, placebo-controlled, multi-center phase 2 trial to evaluate the safety and efficacy of novel host-directed therapeutic agents in hospitalized patients with ARDS. Respondents may address one or more of the following areas and submit responses to the following questions:

3.1 Specific questions to potential organizations that could implement the proposed clinical trial

BARDA is seeking organizations that could implement the platform clinical trial outlined in the Draft Protocol Synopsis in this RFI. The proposed team must include the following entities and experience:

• The management team should have significant successful pharmaceutical clinical trial experience in leading FDA-regulated trials to include phase 2 and phase 3 therapeutic interventional trials with oversight in trial activities in a US-based study. At least 5 years of experience in critical care setting managing ICU patients is required. 
• The management team must be capable of submitting and being designated as the IND sponsor with the FDA including the initial IND for the clinical study, management of safety reporting and submission of safety reports, annual reports and all information requests received from the FDA.
• The management team must include overall program/project management, protocol development, medical writing and report publishing, site identification, site monitoring/management, statistical/data management, safety oversight including the establishment of the safety monitoring committee, budget management, and quality functions.
• The management team may either provide services or provide oversight and management of subcontracted experienced CROs for the above functions.
• The management team must include oversight for the management of study samples and investigational products as well as other clinical trial supplies.
• An experienced pharmaceutical CRO must be included in the management team to ensure robust clinical monitoring as well as data quality and integrity. At least 5 years of experience in the critical care setting managing ICU patients is required.
• All data generated from this trial must be provided to BARDA in a machine-readable format for pooled biomarker analysis and subsequently published in peer-reviewed literature.

BARDA would like to understand if there are entities interested and capable of carrying out the platform clinical trial outlined in the Draft Protocol Synopsis. Please respond to the following questions and topics of interest:

1. Please describe the magnitude of your experience, expertise, and existing infrastructure, related to resources or services needed to meet the requirements. Include references demonstrating this requirement plus additional pages for the following: 

    a. New, novel, or innovative methodologies and approaches for the design of a clinical trial platform study, including experience, resources, and services that would be required as well as potential partner organizations and their potential responsibility for the project. 

    b. Technologies you think would be most useful to the requirement. 

    c. Capabilities your organization can provide in support of this type of trial in relevant therapeutic areas.

    d. Any biomarker experience and plan to conduct or subcontract out this work. 

    e.  Data management and statistical capabilities should include an interactive randomization system, eCRF and clinical database CDISC compliant SDTM and ADaM datasets and statistical design and analyses.

2. Does the protocol synopsis as written present barriers to implementation? If so, please describe potential barriers and constraints to executing a clinical trial platform study as designed to evaluate therapeutic candidates for treatment of ARDS in hospitalized patients.

        a. The Respondent can propose changes to the Draft Protocol Synopsis, including but not limited to the protocol design, sample size, inclusion/exclusion criteria, and proposed biomarker collection. 

        b.  The protocol is expected to enroll the first subject within six to nine months from contract award. The period of performance is three years. To provide the best result, the Respondent can propose changes to the expected timeline with justification.

3.  Describe your organization’s capacity to participate in this type of trial. 

4. Describe your organization’s experience in being designated as the IND sponsor with the FDA, including the initial IND for the clinical trial, management of safety reporting, and submission of safety reports, annual reports, and all information requests received from the FDA. Please note any experience as the IND sponsor of clinical trial platform studies. 

5. Describe your organization’s experience in managing hospitalized patients with critical illness and conducting clinical trials in the intensive care unit. 

6. Provide information regarding the feasibility of accessing this study population and type and number of sites needed to complete the trial expeditiously in the continental United States. 

     a.  Is your organization able to identify 50 sites capable of conducting a clinical trial platform study in patients hospitalized with  ARDS? Please provide information on existing sites within your organization that have ARDS clinical trial experience or the  need for bringing on new sites that have ARDS clinical trial experience. 

7.  Once study product for any given cohort is available, please comment on a realistic timeframe to complete enrollment for any given cohort. 

       a. How long will it take to identify one site, stand it up, and begin enrollment? 

        b. How long will it take to identify 50 sites, stand them up, and begin enrollment? 

8. Please provide a rough order of magnitude for the cost of the trial as proposed in this RFI and a cost for any changes recommended by you. What is further information you may need to develop a cost estimate?

9. Are there aspects of the protocol synopsis that significantly increase costs, inhibit clinical sites from enrolling into the study and/or delay study completion? Please explain.

10. What’s the best contracting vehicle for the proposed work (contract, cooperative agreement, other transaction agreement, or other)? Please provide a rationale for your response.

11. Ideally, there will be triggers for treatment. Will the requirement for diagnostic testing and analysis prior to randomization hinder the conduct of this trial?

3.2  Specific questions to the companies interested in having candidate therapeutics assessed in the proposed clinical trial

BARDA is interested in assessing up to three products in the phase 2 platform trial outlined in the Draft Protocol Synopsis in this RFI. To be eligible for participation in the clinical study, a candidate therapeutic must meet the following criteria:

• Have an open IND or IND application filed with the US FDA for ARDS treatment and be ready for phase 2 clinical studies.
• Have clinical materials (both active drug and matched placebo) labeled for use in a clinical trial and must be available at the time of projected study start, Q1 or Q2 2024.
• Have a host-targeted mechanism of action that is relevant to the treatment of ARDS. Drugs with only an antiviral or antimicrobial mechanism of action will not be considered.
• Be willing to support the regulatory needs of the clinical study team by providing the Investigator's Brochure (IB) and help create an agent specific appendix for the master protocol.
• Data generated from the clinical trial will be published in the peer-reviewed literature. Product sponsors must agree to sharing the data openly once data analysis is complete.

Before finalizing the study protocol, BARDA would like to understand industry interest in the study as outlined. Please respond to the following questions and topics of interest if you have a drug that could potentially be included in the platform trial outlined in the Draft Protocol Synopsis:

1. What is your candidate therapeutic, and what is the mechanism of action as it relates to ARDS?
2. What is the proposed route of administration, dose, and duration of treatment for your candidate therapeutic to treat ARDS?
3. What is the existing preclinical and clinical data supporting the use of your candidate therapeutic for the treatment of ARDS?
4. Can you provide blinded study treatment and placebo for such a study?
5. Have you already identified a potential biomarker or trigger for treatment for your candidate therapeutic? Please discuss the data supporting your hypothesized biomarker and whether an FDA-cleared diagnostic is available.
6. Currently, the protocol has a primary endpoint at 30 days. Is there a reason to extend to 60 or 90 days? Please provide some rationale for why or why not extending the study to 60 or 90 days is desirable.
7. Would you support an interim efficacy and futility analysis for your drug?
8. Would you be interested in collecting imaging biomarkers (e.g., CT, chest x-ray) as novel exploratory endpoints?
9. The protocol synopsis as written stratifies patients between those with mild ARDS from those with moderate or severe ARDS, defined as requiring mechanical ventilation or ECMO. Is further stratification between mild and moderate ARDS needed? Are you interested in enrolling the mechanically ventilated patient population? Please explain the rationale behind your responses.
10. BARDA is interested in data from all levels of ARDS severity. Would you only limit the enrollment of your product to one category of ARDS severity? Are you willing to accept limits on enrollment into particular ARDS severity categories?
11. Are there any concerns with the protocol synopsis as written that make the study less desirable to participate in? If so, please outline your concerns.
12. If you have a drug that has the potential to treat ARDS, but you are unwilling to participate in the trial, please explain the main barriers to your participation.

4.0 Responses

4.1 Interested parties are requested to submit a written response to this RFI.

4.2 The written response shall adhere to the following:

• An electronic format compatible with either the Microsoft Office software package or Adobe Acrobat; and
• The response shall consist of Parts I and II and must be submitted via email only to the individual(s) identified in Section 6.0 Submission below.

Proprietary information, in any form, if any, should be minimized and MUST BE CLEARLY MARKED. To aid the USG, please segregate proprietary information. Please be advised that all submissions become USG property and will not be returned.

Information marked as “Proprietary” obtained in response to this RFI will be protected from unauthorized disclosure in accordance with FAR Subpart 15.207, applicable law, and HHS regulations. However, all information submitted under this RFI may be used to further develop and refine the design and conduct of the proposed phase 2 platform trial to investigate pathogen-agnostic host-directed therapies and collect associated biomarker data for identifying specific subsets of patients for the treatment of ARDS.

4.3 Part I of the written response shall provide administrative information, and shall include the following at a minimum:

4.3.1 Name, mailing address, overnight delivery address (if different from mailing address), phone number, fax number and email of designated point of contact.

4.3.2 Recommended contracting strategy

4.3.3 Business type (large business, small business, small disadvantaged business, 8(a)-certified small disadvantaged business, HUBZone small business, woman-owned small business, veteran-owned small business, service-disabled veteran-owned small business.)

The North American Industry Classification System (NAICS) Code(s) are as follows:

325412 – Pharmaceutical Preparation Manufacturing; and

325414 – Biological Product (except Diagnostic Manufacturing.)

4.3.5 The facility security clearance of the responder (if applicable.)

The number of pages in Part I of the written response shall not be included in the 10-page limitation, i.e., the 10-page limitation applies only to Part II of the written response.

4.4 Part II of the written response shall answer the questions asked in Section 3.0 Requested Information of this RFI and shall be limited to 10 pages.

5.0 Industry Discussions

BARDA representatives may or may not choose to meet with potential responders. Such discussions would only be intended to get further clarification or possible capability to meet the potential USG need.

6.0 Submission

Questions and comments regarding this RFI must be received no later than:

5:00 PM EDT on Friday, September 16, 2022.

Electronic responses to this RFI are due no later than:

5:00 PM EDT on Monday, October 17, 2022.

Your written response shall be submitted to the following individuals:

Lavivian Peasant, Contracting Officer

Division of Contracts Management and Acquisition (DCMA)

Biomedical Advanced Research and Development Authority (BARDA)

E-mail: [email protected]

and 

Jill Johnson, Contracting Officer

Division of Contracts Management and Acquisition (DCMA)

Biomedical Advanced Research and Development Authority (BARDA)

E-mail: [email protected]

Please include RFI No HHS-22-BARDA-RFI-ARDS-001 in the subject line of all correspondence.

All technical and administrative correspondence and questions regarding this announcement shall also be submitted to the above email address.

BARDA intends to use electronic mail for all correspondence regarding this RFI.

7.0 Summary

THIS IS A REQUEST FOR INFORMATION (RFI) ONLY to seek feedback and input on A PHASE 2 PLATFORM CLINICAL TRIAL INVESTIGATING HOST-DIRECTED THERAPIES FOR ACUTE RESPIRATORY DISTRESS SYNDROME. The information provided in the RFI is subject to change and is not binding on the USG.

BARDA has not made a commitment to procure any items or services, and the release of this RFI should not be construed as such a commitment or as authorization to incur the cost for which reimbursement would be required or sought.  All submissions become USG property and will not be returned.

This RFI is in accordance with FAR 52.215-3 Request for information or Solicitation for Planning Purposes (Oct 1997). As such, any information received will be for the purpose of planning only.

Attachments/Links

The Draft Protocol Synopsis has been added