Informational Webinar for Applicants to NINDS ALS Expanded Access (U01)

February 15, 2023 | 3:00 - 4:00 PM

 

Contact:   Jane Hettinger
Location: The webinar is open to the public, but registration is required. 

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Informational Webinar for Applicants to NINDS ALS Expanded Access (U01)
Register for the webinar on February 15, 2023 | 3PM - 4PM
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Informational Webinar for Applicants to NINDS ALS Expanded Access (U01)
Register for the webinar on February 22, 2023 | 3PM - 4PM

These webinars aim to inform and answer participant questions on the NINDS Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required) RFA-NS-23-012. The goal of this announcement is to support the conduct of scientific research utilizing data from expanded access (EA) for investigational drugs or biological products for patients living with ALS who are not eligible for ongoing ALS clinical trials. These webinars will provide an overview of the funding opportunity, including requirements and eligibility, and will include a Q&A session.

All investigators interested in learning about the NINDS ALS Expanded Access program are encouraged to register and participate. You are also encouraged to submit questions before the meeting to Jane Hettinger.

The receipt date for this ALS Expanded Access Funding Opportunity is March 23, 2023.

Frequently Asked Questions

The Accelerating Access to Critical Therapies (ACT) for ALS Act was passed into law on December 23, 2021 (P.L. 117-79). Section 2 authorized a grant program for scientific research utilizing data from expanded access to investigational drugs for individuals who are not otherwise eligible for clinical trials for the prevention, diagnosis, mitigation, treatment, or cure of amyotrophic lateral sclerosis (ALS). The statute limits the grant program to phase 3 clinical sites sponsored by a small business concern.

NIH has released RFA-NS-23-012 in fiscal year 2023 to implement Section 2 of ACT for ALS. In the below frequently asked questions (FAQs), we have pointed out the relevant sections of ACT for ALS that establish the requirements of this NIH grant program.

Eligibility Requirements See ACT for ALS Sec. 2(e) for definition of participating entity and participating clinical trial, and Sec. 2(a) for expanded access New Drug Application (IND) authorization requirements.

Q: How is small business concern eligibility determined?

A: A “small business concern” is defined by section 3(a) of the Small Business Act (15 U.S.C. 632(a)).

Q: Can the small business concern drug sponsor apply directly to RFA-NS-23-012?

A: No. Consistent with the ACT for ALS, the RFA states that “Eligible applicants must be clinical trial sites that participate in a phase 3/efficacy clinical trial supported by a small business concern that is the FDA-designated sponsor of a drug or biological product which is the subject of an IND under section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)) to prevent, diagnose, mitigate, treat, or cure ALS.”

Q: How is NIH interpreting the “phase 3 clinical trial” requirement? Are phase 2/3 trials eligible? What about phase 3 trials that have concluded but are awaiting regulatory consideration?

A: Phase 2/3 trials, ongoing phase 3 trials, and concluded phase 3 trials are eligible until a regulatory determination has been made regarding approval. As noted in the RFA, and consistent with the ACT for ALS, the investigational drug proposed under RFA-NS-23-012 must not be approved under a New Drug Application (NDA) or licensed under a Biologics License Application (BLA).

Q: Does the qualifying ALS phase 3/efficacy clinical trial need to be ongoing at the time of application?

A: The IND for the ALS phase 3/efficacy clinical trial must be active at the time of award for applications selected for funding under RFA-NS-23-012.

Q: We have a large number of participating clinical sites in our study. Do we need site interest letters signed by all participating sites? Do signatures need to include the Business Official and Principal Investigator (PI)?

A: While interest letters are not required for all participating sites, they are recommended, particularly when recruitment may be a potential issue in the proposed study. While signatures from both the Business Official and PI are recommended, the PI signature alone is adequate.

Q: Are patients already being treated under an ongoing intermediate-sized EA INDs eligible to be included in the studies of that same intervention proposed under RFA-NS-23-012?

A: Inclusion of patients currently treated under existing Intermediate-sized EA INDs may participate in studies proposed under RFA-NS-23-012 if their inclusion may aid proposed research goals. However, applicants are strongly recommended to expand existing EA INDs and prioritize resources to support the addition of new patients not currently treated through expanded access.

Q: How does FDA’s review of expanded access requests intersect with NIH’s grant approval process?

A: EA IND authorization is conducted through the FDA. Per the RFA, applicants to RFA-NS-23-012 must submit their EA IND by the time of application, and the EA IND must be allowed to proceed prior to award. NIH is not involved in the review or authorization of EA INDs.

Q: Can RFA-NS-23-012 support studies approved under Open Label Extensions?

A: No, studies under Open Label Extensions would not be eligible per the RFA. The proposed study must be conducted under an intermediate-sized EA IND that is in effect.

Q: What is the expected size of an intermediate-size patient population for expanded access?

A: FDA considers an intermediate-size patient population for an EA IND to be when more than one patient, but generally fewer patients than are treated under a typical treatment IND or  protocol, will be treated with an investigational drug/biological product under the EA (21 CFR 312.315).

Q: Will the grant funding available help fund clinicians and clinic staff who often incur the direct and ancillary costs of administering expanded access programs?

A: Costs associated with the treatment and research proposed under RFA-NS-23-012 are eligible per the RFA, the following costs are allowed:

Payment to the manufacturer or sponsor for the direct costs of the investigational drug or biological product of the intermediate EA protocol for ALS, as authorized under section 312.8(d) of title 21, Code of Federal Regulations (or successor regulations)

  • Direct costs incurred in providing such drug/biological product consistent with the research objectives of the grant
  • Direct and indirect costs of participating clinical trial sites in conducting research with respect to such drug/biological product
  • Personnel effort, support for study participant travel/meals, and other budget items within the overall budget cap to ensure that this goal of appropriate inclusion is met

Q: Will there be future funding and future RFAs to support this effort?

A: FY23 funding has been appropriated by Congress for implementing ACT for ALS. Future funding and future RFAs will be determined by congressional appropriations for this program. As with all NIH-funded awards, funding of future years depends on availability of funds.

Q: Will the community have an opportunity to weigh in on what research questions they would like NIH to require?

A: Per the RFA, applicants are strongly encouraged to establish relationships with patient advocacy groups and solicit their input on recruitment (including equitable access to investigational drugs by minority and underserved populations), the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study participants. Additionally, NIH will include people affected by ALS (people living with ALS, caregivers, or people at risk for developing ALS) in the Scientific Review Group (also known as a study section) that is the first level of review for applications.

Inquiries
Please direct all inquiries to:

Emily Caporello, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)/Division of Translational Research
Email: emily.caporello@nih.gov

Lumy Sawaki-Adams, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)/Division of Clinical Research
Email: lumy.sawaki-adams@nih.gov

Amelie Gubitz, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)/Division of Neuroscience
Email: gubitza@nih.gov