Seeking Ideas for Therapeutic Trials - Phases Ib-III

Infrastructure includes expertise in study design and conduct, and full clinical trial management capability at our coordinating center and network of trial sites. Although ACTC Member Sites are invited to join each project, proposals are not required to utilize all 35 ACTC Member Sites. Projects may also select additional sites, where needed. Review the Funding Opportunity Announcement (FOA) from NIA.

The review and feedback process is approximately 8 weeks. Grant development timelines depend on the stage of the study and level of input needed to complete a competitive application. Proposals go through the following levels of review to assess strength of proposal and appropriateness for ACTC. Feedback is always provided to applicants.

Yes. NIA strongly endorses the idea of public private partnerships and ACTC projects can be with academic investigators, biotech companies, small companies, or with Big Pharma through a public private partnership. We want to partner with the community, as you said, for pharmacological interventions of different sized companies, and different size academic sites.

For the application itself, the answer is no. Language will often say that letters of intent are encouraged, but not necessarily required. In this case, because there’s so much work that’s done ahead of when an application comes in, we really don’t even have to worry about that, because anything that’s coming through is already vetted by ACTC and is coming forward as an application, whether it be collaborative or from the ACTC itself.

We’re planning on roughly five to seven for the life of the current grant cycle of the ACTC. As far as what the funding amount is for the actual trial, that is dependent on what the trial needs. Right now, there’s not a cap on the amount that can be asked for in an application. NIH has some clearances and things that are normal with grants, and anything over $500,000 direct costs in any year, must go through a clearance by the Institute, but that’s a very routine process.

The first two months of that five months involves the review steps within the ACTC; a feasibility review, a scientific review, and then consideration by the Steering Committee, which typically involves a presentation from the proposer to the Steering Committee with both open and closed discussion. Those review steps occur over six to eight weeks. Most of the five months is taken up by the collaborative development of the R0I grant application, which is a collaboration between the proposer of the idea and the ACTC, involving all the relevant units and committees of the ACTC that takes up the bulk of the time. In total, most likely 10 months or longer.

ACTC would not be appropriate for a standard, first in human, single ascending dose/multiple ascending dose phase one trial design. That would be more appropriate to a standard phase one, a CRO. Trials that are done by ACTC should be studies that take advantage of the ACTC infrastructure, particularly around AD or cognitive assessments, CSF sampling, imaging. A typical first in human study would not take advantage of the expertise of ACTC. So when we say phase one, we really mean phase 1b. Studies that are small and might even be the first in human, but they are aiming to establish a pharmacogenomics mechanism, so a multi-site early phase CSF sampling study to explore CNS penetration and impact on AD biomarkers would be appropriate for ACTC. Certainly, phase two and phase three studies would be typical for the ACTC multi-center trials with either biomarker outcomes, cognitive and clinical outcomes, or as most common, all the above. And certainly, we aim to be involved in any way that’s useful to the people that proposed the project, and that includes long term planning and follow-on studies as well.

There’s no rule about this, and particularly for repurposing of drugs, we would often pursue arrangements to refer to existing IND submissions or existing files at the FDA. For a new chemical entity, typically there would be an IND held by the applicant or the developer of the new chemical entity, but we’re open to discussing any regulatory approach.

For data sharing, we are following the cap principle. That means all pre randomization data will be shared within 12 months of the last participant randomized, and then all study data will be shared with the scientific community after either regulatory approval, or 18 months after the completion or early termination of a trial. Of course, that means that all our data will be anonymized prior to sharing. Any data sharing also will be considering any of the proprietary data; we work out these data sharing plans in partnership it with the pharmaceutical or academic partner.

We’re very interested in testing a diversity of mechanisms. Any application first must be appropriate for the ACTC, meaning that it must fit in with the expertise of the ACTC sites and investigators, and take advantage of the ACTC infrastructure that covers a lot of ground. Pretty much any multi-site study in AD or an age-related dementia at phase two should be appropriate for the ACTC. But the review process goes beyond feasibility and considers scientific merit and then involves interaction with our Steering Committee. We are very eager to test non-amyloid-related mechanisms, whether they are standard mechanisms like anti-tau, or micro-glial mechanisms, or neuro-protective mechanisms, or something entirely novel. We welcome all such suggestions.