NIH – Clinic Testing Therapeutic/Indication Pairing Strategies (U01 Clinical Trial Required)

October 24, 2017 by School of Medicine Webmaster

Discoveries that clarify the molecular basis of disease provide unprecedented opportunities to translate research findings into new medicines. However, developing a new medicine takes an enormous amount of time, money and effort, mainly due to bottlenecks in the therapeutic development process. Delays and barriers mean that translation of a promising experimental therapy into an approved drug often takes a decade or more.  NCATS intends to support strategies that reduce delays, decrease costs and improve success rates.

Drug repurposing/repositioning is one such strategy. Many existing experimental drugs, FDA approved drugs, and biologics already have been tested in humans, and detailed information is available about their pharmacology, formulation, and potential toxicity. By building upon previous research and development efforts, new uses for existing experimental drugs or FDA approved drugs can be advanced to testing in clinical trials more quickly than starting from scratch. If a new therapy receives regulatory approval, it can be efficiently integrated into clinical practice.

NCATS focuses not on specific diseases, but what is common among them and the translational science process. NCATS mission is focused on process improvements (new technologies/approaches to accelerate the process of getting more treatments to patients), by developing and deploying solutions that can be used by all translational science researchers. In doing so, NCATS complements other NIH ICs that also support translational research in disease-specific areas.

For this funding opportunity announcement (FOA), NCATS is interested in clinical studies that demonstrate utility of an approach for identifying new therapeutic/indication pairs. The strategy should be applicable to other diseases, so that successful use of the method can improve the efficiency of predicting new indications for existing therapeutics.

Research Objectives and Scope

This FOA intends to support clinical testing of innovative ideas for the discovery of new therapeutic uses of existing drugs/biologics in previously unexplored diseases. Proposed human trials can include: 1) use of an existing drug or biologic as a stand-alone intervention; or 2) use of an existing drug or biologic as an adjunctive intervention with existing standard of care (if there is no evidence of drug-drug interactions with the proposed standard of care treatment).  In either case, this initiative will support clinical trials on a therapeutic/indication pair, which was identified with a published or publicly available computational algorithm, or publicly available independent crowdsourcing strategy to identify a new therapeutic/indication. The method should already be published or publicly available, so it can be disseminated to improve data usability for future repurposing studies.

Phase II clinical trials may be proposed for a common disease. If needed, Phase I clinical trials may also be included for the new indication for a common disease.  Rare disease trials should follow Draft FDA Guidance: “Rare Diseases: Common Issues in Drug Development Guidance for Industry”. Specifically, one or more adequate and well-controlled clinical trial(s) may be conducted in a rare disease population.

Strategies to inform the selection of patients for proposed new uses of the therapeutic area are of interest.

For this FOA, NCATS will use the following definitions:

  • Crowdsourcing: Crowdsourcing occurs when an investigational drug is publicly posted for investigators to propose ideas for new therapeutic uses. Generally, crowdsourcing is an approach used for investigational therapeutics, not therapeutics approved by the FDA, since approved drugs already are known to the public.
  • Computational algorithm: A computational algorithm is the business end of bioinformatics. A computational algorithm will mine existing data and identify therapeutic/indication pairs for experimental investigation.
  • Published or publicly available method: A published method is generally one that is in a peer-reviewed publication. A publicly available method could be available via a website or a commercially available product. The publicly available strategy does not need to be free, but it should be available to investigators that would like to use it.
  • Phase I clinical studies are conducted in the target patient population to evaluate safety, determine a safe dose range, and identify side effects prior to conducting a Phase II clinical trial.
  • Phase II clinical trials are conducted in a larger patient population, typically 150 subjects or less for trials in adults. The purpose of the Phase II clinical study is to provide a preliminary signal of efficacy.
  • Rare Disease: A disease or condition that affects fewer than 200,000 people in the U.S.
  • Common Disease: Any disease or condition that is not a rare disease.
  • Clinical trials for Rare Disease: Due to small numbers of available patients, the terms Phase I, II and III clinical trials may not always be appropriate.  Therefore, well-controlled studies in a rare disease population may be proposed to demonstrate substantial evidence of efficacy in treating or preventing the condition and to establish evidence of safety for that use. Evidence of efficacy for a rare disease may be established in one or more adequate and well-controlled clinical trials in the identified population. See Rare Disease: Common Issues in Drug Development Guidance for Industry for more information:

Clinical trials should use the selected therapeutic in its existing formulation/route of administration. The only exception is for pediatric indications, which may need to be formulated as a solution/suspension for oral administration (ages 6 to 11) or a small tablet/capsule (ages 12 to 18). Palatability issues also may have to be addressed for pediatric administration.

Phase I clinical trials may be needed for the new indication, depending on what is already known about the drug. Projects that propose early stage Phase I clinical trials for the new therapeutic use are expected to be completed within 12 months and should be designed to accomplish the following:

  • Inform patient selection criteria.
  • Identify an appropriate dose(s), drug exposure at the target site to use in the proposed patient group, and evaluate safety, and tolerability prior to conducting a Phase II clinical trial in a larger population.

Transition from Phase I to Phase II clinical trials is dependent on meeting Phase I milestones, listed in the Notice of Grant Award. Progress from the dose-finding safety and tolerability clinical trial to the Phase II efficacy signal trial is generally assessed at the transition from year 1 to year 2 of the award. Phase II clinical activities will include milestone-driven trials that are designed to detect a preliminary signal of efficacy to inform a decision on progressing to the next phase of development. The total clinical trial period is up to three years.

Due to small numbers of available patients, the terms Phase I, II and III clinical trials may not always be appropriate for rare disease studies. NCATS can support milestone-driven rare disease trials to establish evidence that establishes safety and efficacy for a total clinical trial period up to three years. See Rare Disease: Common Issues in Drug Development Guidance for Industry for more information: Applicants are strongly encouraged to have prior consultation with NCATS staff regarding the determination of whether proposed activities meet the criteria for Phase III rare disease or condition trials.

Organizations involved in the research project must be identified at the time of application. Prior to application, the applicant organization must provide documentation that they have or will have access to the drug/biologic that will be used in clinical studies. To help ensure rapid transition to future Phase II clinical trials, the therapeutic must have completed Phase I clinical testing in humans for a different indication by the time an award is made.

Because the abstracts will be published upon award of a grant, applicants are encouraged to discuss with collaborators and their institutional technology transfer office to ensure the abstract content will not constitute disclosure of intellectual property and proprietary information.

NCATS strongly encourages applicants to involve patients or their representatives in the planning of the trial, as appropriate.

Deadlines:  Standard dates apply.


Filed Under: Funding Opportunities