PPMD is committed to making research and development of new medicines for families living with Duchenne as fast and efficient as possible.  Over the years, by listening to you, we have developed a clinical trials imperative that we strive to live up to.

• Trials should not be limited to a subset of patients, but rather inclusive of young and old, ambulatory and non-ambulatory, those on steroids and those who are not.
• Exposure to placebo should be limited or non-existent.
• Trials should end quickly if they are not showing positive results and participants should be given another opportunity in a timely manner.
• Efficiencies are needed across clinical trials, including contract negotiation, a single Institutional Review Board (IRB), standardized protocols and outcome measures, opportunities for combinations, and faster approvals.

As part of making these imperatives a reality, PPMD is evaluating a master protocol for Duchenne, along with community stakeholders, and has partnered with the Institute for Advanced Clinical Trials for Children (I-ACT) to address the complex issues that running a large trial with multiple therapies entails.

The term master protocol is the general name for a trial that can study more than one experimental therapy at a time, and/or multiple patient populations, at once. This is quite different from how studies have traditionally been conducted in Duchenne and elsewhere. There are several different designs of master protocols and all are used for a different purpose. For Duchenne, a platform design makes the most sense, as it allows multiples therapies to be studied at the same time. As we explore this concept, we will use the term “platform trial” interchangeably with master protocol.

This summer, FDA Commissioner Scott Gottlieb communicated some of the key ways the FDA is thinking about streamlining the clinical trial process. Commissioner Gottlieb mentions master protocols and platform trials as potential solutions. He also mentioned creating “continuous trials” in which the wait time between some phases (sometimes as long as a year or more) is eliminated. He talked about the need to reduce “endpoint” creep – the tendency to include many non-essential outcomes in a trial – making it lengthy and difficult for patients. Our newly formed Duchenne Trial Consortium – made up of PPMD and I-ACT, with regulatory support from the Critical Path Institute (C-Path) – is already one step ahead of the game, as many of the concepts Commissioner Gottlieb mentioned are being incorporated into our platform trial design.

Who is I-ACT?

Exploring, designing, and executing a complex trial like a platform trial is not easy and takes many different skill sets. For this reason, partnering with an organization like I-ACT was a natural next step, as they bring a diverse set of competencies to the table.

I-ACT is an independent nonprofit organization that works with public and private stakeholders to improve the planning and completion of pediatric clinical trials. It facilitates advanced research and education directed at improving the timeliness, quality, and medical impact of clinical trials of innovative therapeutics for children. I-ACT was established by C-Path with guidance from its Pediatric Trials Consortium, which included more than 30 diverse organizations such as patients/parents, government agencies, professional organizations, academia, the biopharmaceutical industry, and international experts. As you may remember, PPMD has a long history with C-Path, whom we continue to partner with on the Duchenne Regulatory Science Consortium (D-RSC).

Exploring Ongoing Platform Trials

I had the privilege of planning and participating in a recent workshop organized by the DIA (the Drug Information Association) on master protocols. The meeting provided an overview of master protocols and how/why they have evolved, described some of the key elements that drive the trial design and statistical plan, and reviewed some ongoing trials as case examples. The session I chaired and spoke during was on collaborations. It focused on understanding how different sets of stakeholders react to platform trials, the importance of applying change-management principles and insight from other technology-adoption cycles from different sectors, and the need to prioritize a patient-centric vision to overcome various challenges.

FDA Center for Drug Evaluation and Research (CDER) Director Dr. Janet Woodcock closed the workshop by saying that master protocols are the way trials will be conducted in the future – resulting in better care and treatments for people and lowering the cost of drug development to a sustainable level. She emphasized that what we are doing now is not sustainable. (To learn more about her thoughts on platform trials, click here.)

Throughout the workshop, I was struck by several thoughts:

1. Facilitating any collaboration, including collaborative trials, is hard and takes time to set up! This was repeated several times by different people and was reinforced by the fact that several of the trials that have been mentioned since I have been involved with master protocols are just now getting started. Yet while everyone mentioned that they are difficult, they are happening, and those involved are not giving up, because they are the right thing to do for patients.
2. When they get going, they really snowball. As with many things, all it takes is one early adopter and then others join, as they don’t want to be left behind.
3. Every illness is different and no platform trial is going to be identical nor have the same challenges.
4. What all these master protocols are doing – I-SPY 2 in breast cancer, GBMagile in glioblastoma, PANCAN in pancreatic cancer, EPAD in ALS, DIAN TU in Alzheimer’s – are innovating for patients. Families affected by Duchenne deserve this same creativity and visionary thinking.

I left the workshop inspired by being part of a committed, dedicated group of smart scientists who are leading the charge in transforming how clinical trials are being conducted for the future.

Why a Duchenne Platform Trial May Work in Duchenne

Many families in our Duchenne community are familiar with the complicated and often frustrating clinical trial process. PPMD has been thinking about this for a long time. How can we make clinical trials faster, less burdensome, and open to all mutations, no matter the stage of disease? Is it possible to understand someone’s response to a compound or biologic (intervention) more quickly? Would it be possible to minimize the number of participants on placebo? To initiate testing of combinations of promising therapeutics earlier?

Today, most Duchenne trials are designed to answer one question: How does one drug compare to placebo in a chosen patient population? Clearly, sticking with this trial design is not going to improve clinical trials and our understanding of Duchenne. This is why we are interested in the platform trial idea — a trial designed to study multiple different drugs in multiple patient types with one common placebo-controlled arm.

Since 2016, PPMD has been closely examining the potential of a master protocol for Duchenne, including studying the history of this concept in other diseases, having in-depth discussions with clinical   trial experts who have developed master protocols, and thinking about the potential of a platform trial for Duchenne.

PPMD, along with a group of community stakeholders who answered our call for volunteers, have been exploring the idea of a Duchenne platform trial because we believe that ending Duchenne will require innovative new options and thinking outside the box. A platform trial may make the clinical trial process more efficient – which is especially important with a rare disease such as Duchenne, which has a small population of patients to recruit. This has the potential to limit both risk and disappointment.

We look forward to listening to the Duchenne community and addressing your questions with our partners at I-ACT and we will continue to keep you updated on what we discover. Please connect with us at abby@parentprojectmd.org.  Meanwhile, we continue to plan for an Open Public Meeting about the trial in spring 2019, where all interested members of the community can discuss this opportunity.

Learn more

To learn more about platform trial, watch the webinar PPMD hosted below. With this webinar, we provided basic information regarding the master protocol concept, its pros and cons, and how it might impact families. We also share what we have learned so far, providing an update on potential next steps, and talk about how you can not only add to the conversation, but also become an active participant in our continued exploration of this concept.