Are You Planning To Run Hemophilia A Trial?

Are You Planning To Run Hemophilia A trial?

We may all agree that identifying the right regions and countries is a core stone for clinical trial success. And while for some indications there might be several equally good options, the importance of selecting the right regions is more than obvious when we talk about indications such as Hemophilia A (HA).

The importance of selecting the right countries was confirmed once again in our recent research, which showed that some regions were absolutely no go when it came to clinical trial planning for that particular indication and the study drug. According to the research, placing the study in some countries would be like going to winter skiing vacation to Maldives, and would set this clinical trial for a failure. We have identified two critical factors for study success, and they are related either to competition or to the study drug. In case you are wondering what makes competition or the nature of the study drug so critical for study in severe HA, whether this is something important for all clinical trials, and how this can be useful for you, keep reading.

Site Level Survey

In our recent research we interviewed 198 sites across US and Europe to gauge their interest in clinical trial for testing efficacy of a classical replacement recombinant factor with a standard half-life in on-demand treatment of bleedings in previously treated adult male patients with HA, planed for 2019/2020. Although we received responses from 184 sites, only 38 sites (26%) expressed their interest to participate (Figure 1).

Figure 1. Site Interest Chart

It was a very important finding of this research that no interested sites were identified at all in more economically developed countries, while sites from less economically developed countries were more inclined to participate in the study.

Site Interest

The highest percent of sites (25% of sites) refused to participate in the study due to ongoing or planned competing trials in hemophilia A, while 18% of them commented that they would be more interested in participating in clinical trials investigating novel therapeutics for hemophilia.

Therefore, as high as 43% of the sites declined due to the reasons related to competition. These sites reported either having some ongoing or planned competing trials for hemophilia or said that they would prefer participating in clinical trials with more advanced treatment options for their patients. And this came as no surprise, as the US and Western Europe are the regions with the highest number of ongoing and planed competing trials worldwide at the moment. And many of them are investigating novel treatment options that have the potential to enhance the standard of care by decreasing infusion frequency to increase compliance, promoting prophylaxis, offering alternatives to inhibitor patients, and easing route of administration.

21% of the sites commented that their patients had better treatment options available at their sites, for which reason their interest in a classical replacement recombinant factor with a standard half-life would be high enough. The field of novel therapeutics for hemophilia has seen significant advances in recent years. Several extended half-life (EHL) products are already available in many countries, while others have classical replacement recombinant factors available at no costs for the patients, which matches the results of our research.

8% of the sites pointed out limited recruitment potential (8%) as a reason for decline, while 3% of them declined due to various administrative issues which were not related to the study (5%).

A comprehensive list of decline reasons is provided in the Figure 2 below.

Figure 2. Decline Reason Chart

Competitive Clinical Trial Market

We may all agree that conducting a detailed competitive analysis before selecting specific countries for the particular clinical trial is one of the most important part of successful planning. In addition, our experience with 43% of the sites that named competition as a reason for decline confirms again the importance of a detailed competitive landscape analysis.

Accordingly, you may ask, what trials will compete for adult hemophilia A patients in 2019? What trials will be trails of high risk for planned adult hemophilia A trial in 2019, and which ones will create competition, but entail a low risk, and might not put your study in danger? In real-estate, it is said that what matters are three things, all related to attractiveness: location, location and location. Similarly, in clinical trials, location and attractiveness play an important role too, in addition to patients and timing.

Clinical trials that will be recruiting adult hemophilia A patients, in the same countries, and at a high number of sites, especially if they are investigating promising treatment options and during the same time frame, will be those of the highest risk for the study. We have identified 17 clinical trials falling into this category. All of them are investigating novel treatment options (monoclonal antibody, gene therapy or small interfering RNA therapeutic agent) which makes them more attractive to both patients and investigators. Only five of these trials will be using sites out of Eastern Europe. For all other trials, sponsors have selected sites in the US, Western and South Europe, giving them more options, and making them less interested in standard replacement factor treatment studies, which partially justifies the high percent of sites that declined due to competition.

The second group of competing clinical trials falls into category of trials that will create medium risk. These would be trials that will be recruiting the same patient population, at the same locations, at the same time, and yet, compared to high risk trials, the investigated study drug is not as attractive. We have identified six trials that would be investigating replacement rFVIII, while one would be investigating vWF replacement therapy, one DDAVP Inhalant Product and one combination of Steroid and rituximab. These studies will be placed at sites located in the US and in all regions across Europe.

Timelines for the identified high and medium risk studies are illustrated in Figure 3 below. The timeline of each study is represented by a colored line, which plots the study commencement date to completion date, including any follow-up period required for the patients.

Figure 3. Competitive Study Landscape Filtered

Source: clinicaltrials.gov, modified

Last, but not the least, are clinical trials that will not compete for the same patient population, only for on-site time and resources, as they will be placed at the same sites as hemophilia A trial. These would be all studies in hemophilia, including hemophilia B. Depending on the country, some studies in various bleeding disorders might also fall into this category.

Altogether, 960 trials in bleeding disorders are in progress or are planned to be done worldwide (Figure 4). Having in mind the very high number of trials that are or will be placed in the US (590) and EU (290), and that the majority of European trials will be paced in Western and Southern Europe, it seems reasonable that none of the sites from these locations were interested to participate in the study. More than 100 trials are ongoing or are planned to be done at each France, Spain, Germany, UK and Italy, limiting sites capacities. On the other hand, a significantly lower number of planned or ongoing trials (median of seven trials per country) in Eastern Europe is a strong indicator that these countries might have much more time, resources on one hand, and less options on the other hand, and might be more motivated to participate in the study.

Figure 4. Indirectly Competing Trials: World

Source: clinicaltrials.gov, modified

 

Closing Remarks

Selecting countries without detailed analysis of competition would be like going on winter vacation in the summer, and we might not get what we came for, even when we are at the right location and have selected the high performing sites. Not only that sites will have insufficient time or resources, but patients will have many different treatment options to choose from as well, and might decide to take part in a trial different from yours. Our team is at your disposal to support you should you need a detailed analysis of competition or should you be interested in hearing how best to perform a detailed and accurate analysis of the competitive clinical trial market. You can submit your question HERE.

 

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