Lessons In Pivoting From A Clinical Trial Launch In Uganda

By Catherine Correia, Scott Miller, and Grace Fitzgerald, Gates Medical Research Institute

In January 2025, just days before a malaria clinical trial was set to launch in Uganda, an Ebola outbreak was declared near one of the trial sites. At the same time, supplies of a critical antimalarial drug were nearing expiration, and national malaria vaccine rollout plans suddenly changed — disrupting the trial’s recruitment strategy.

For many clinical programs, any one of these developments could have delayed enrollment for months. Instead, the Gates Medical Research Institute (Gates MRI) and its Ugandan research partners rapidly restructured and redistributed enrollment responsibilities across sites. Adapting operational plans in real time kept the study moving forward without compromising participant safety or trial integrity.

The experience became a powerful example of what successful global clinical trials require beyond scientific rigor alone: agility, contingency planning, and trusted partnerships.

Gates MRI, as an affiliate of the Gates Foundation, accelerates the development and delivery of lifesaving medical innovations to address unmet needs like malaria. Gates MRI sponsored a trial designed to examine the safety of an experimental monoclonal antibody (mAb) that may have the potential to help children and adults in sub-Saharan Africa fend off malaria infections. According to the World Health Organization (WHO), nearly half of the world’s population is at risk of malaria, but more than 90% of the world’s cases and deaths from the disease occur in sub-Saharan Africa.

Antibodies against malaria, either from natural infection or the pediatric vaccines, have shown limited protection. Gates MRI optimized the most potent antibody that exists naturally, modified it to last longer, and administered it directly into patients, much like any other shot.

This approach is particularly useful for the most vulnerable: babies, pregnant women, and people who are immunocompromised and unable to generate sufficient protective antibodies on their own. Cancers and autoimmune disorders have been successfully treated with mAbs, and infectious diseases are an emerging target — but not yet for malaria.

Our trial examined the experimental mAb’s safety profile: where it goes within the body, how long it stays, and its biological effects following malaria exposure. This was a two-part trial: adults enrolled first, followed by pediatric cohorts of 2- to 5-year-olds, 12- to 24-month-olds, and 3- to 12-month-olds, with enrollment of the older children first and the infants last (i.e., an age de-escalation trial).

Selecting The Right Sites

Malaria is the leading cause of death in Uganda, and the country has the third-highest burden of the disease. While the rollout of malaria vaccines across sub-Saharan Africa represented a major public health milestone, it complicated our trial strategy. To accurately evaluate the experimental mAb, we needed participants who were not simultaneously receiving a malaria vaccine.

Site selection for this trial hinged on four factors. First, we required access to a participant population that has exposure to malaria. Second, we needed a country that was not yet rolling out a malaria vaccination campaign for all infants and young children. Third, we required trial sites that performed high-quality research and were very experienced in pediatric research. Lastly, we needed sites that had trusted relationships with their community.

We were fortunate to select two highly experienced sites in Uganda, with a high enough risk of exposure to malaria but not scheduled to take part significantly in the vaccine rollout effort.

Our first site, the International Development Research Centre (IDRC), is located in a year-round high-malaria transmission area. IDRC, utilizing their deep, trusting partnership with the community around their center, has a proven track record of recruiting children and infants for complex trials and maintaining excellent retention. IDRC, due to its high malaria burden, was expected to be included in the initial rollout of the malaria vaccine for children up to 6 months of age. Thus, to evaluate the experimental mAb, we planned for IDRC to significantly contribute to enrollment of adults and children over the age of 6 months.

Our second site, Joint Clinical Research Centre (JCRC), is in the Kampala region, an area considered to have relatively low malaria transmission and was not included in the vaccine rollout. JCRC also brought extensive experience conducting complex trials, strong relationships with their community, and deep experience enrolling children and infants in clinical trials. We planned for JCRC to focus on the young infants and contribute to the older children and adult cohorts.

Challenges In The Landscape

As a prevention trial, all participants first needed to clear any existing malaria infection before receiving the experimental mAb. Uganda, as a region with significant antimalarial drug resistance, required the use of pyronaridine-artesunate, a new antimalarial treatment. The global supply of Pyronaridine-artesunate was limited and the supply available had a short shelf life.

Then the conditions became significantly more complicated.

A couple of weeks before the trial was set to begin, as the investigator meeting concluded and we collectively were racing to complete the final start-up activities, an Ebola outbreak emerged near one of the two trial sites. On January 30, 2025, the Ugandan Ministry of Health officially declared the Ebola outbreak just one week before study planned to start. With this announcement, the trial was formally delayed and would not start until the outbreak was declared over.

At the same time, the expiration clock continued ticking on the limited antimalaria drug supply, requiring us to pivot and compress our planned enrollment timelines.

Concurrently, Uganda reassessed its malaria vaccine rollout plans amid the outbreak response and broader shifts in foreign aid support in early 2025. Health officials expanded vaccine eligibility in the area around the IDRC site to include infants up to 12 months rather than stopping at 6 months, significantly reducing the eligible participant population originally planned for that site.   

The team was forced to pivot again and revise our recruitment strategy.

Pivoting While Maintaining Patient Safety And Data Integrity

Given the three simultaneous challenges — limited antimalarial supply, the Ebola outbreak, and the change in malaria vaccination strategy — we evaluated options for adjusting the trial so that we could still have sufficient population to enroll while maintaining participant safety and trial integrity.

We considered adding another trial location, but the time to activate a new site was incompatible with the short expiration window on the antimalarial drug supply. 

Instead, Gates MRI worked closely with IDRC and JCRC to redesign enrollment responsibilities across the two sites. JCRC agreed to enroll all children up to 12 months, many more than had been expected, to compensate for the reduced infant enrollment ability at IDRC.

We then developed a revised recruitment plan and accelerated timeline.

IDRC prepared to rapidly initiate enrollment immediately after the Ebola was declared over, focusing on the adult and the older pediatric cohorts. JCRC, in turn, partnered with immunization clinics to have a common place to engage families of infants. As this was an age de-escalation trial, JCRC needed to expand their reach to ensure that they could enroll the youngest cohort within an extremely tight timeline from screening to dosing with the investigational product. To achieve this, JCRC developed new relationships at immunization clinics outside of their immediate geographic area.

Following these adjustments, the trial proceeded shortly after WHO declared the Ebola outbreak over, and we completed enrollment 15 days before the pyronaridine-artesunate supply expired. Both sites incorporated their experiences during the COVID-19 pandemic and a prior Ebola outbreak in preparing procedures should Ebola re-emerge during the trial. We are still evaluating the data, but the results will help determine whether the experimental malaria mAb should proceed to more advanced clinical trials.

“When we started, when we were preparing to enroll,” noted Abel Kakuru, the principal investigator for IDRC, “we did community engagement like we always have done. We need the district leadership, the parish leadership, and then the village leadership, including health teams, to help us to recruit. And most of these community leaders already know us, because they have worked with us in other studies. This allowed us to move quickly.”

3 Keys To Success

Our experience reinforced three core principles for navigating the unexpected realities of global clinical research. 

First, clinical trial teams must be agile. Rigid adherence to an original operational strategy can jeopardize a study when conditions rapidly change. Teams must continuously reassess assumptions and adapt plans in response to emerging challenges.

Second, thoroughly plan for all contingencies; identify and understand all risks. Many challenges that emerge are not surprising, and the exercise of planning for them, should they take place, helps reveal solutions for other challenges.

Third, African researcher Kelly Chibale often talks about the need to build equitable partnerships, both at the start and continuing through the trial, which is our last tenet. These partnerships help you handle the situations that inevitably come your way — and help keep small challenges from becoming major issues. The partnerships we built with JCRC and IDRC allowed us to pivot and change operational strategies rapidly. Without these relationships, we would have lost too much time in the planning process and critical supplies would have expired.

Global clinical research depends on more than protocols and timelines. It requires sustained local partnerships, shared decision-making, and continuous communication with the communities and investigators closest to the work. Those relationships ultimately made it possible to adapt quickly when conditions changed.

“The people who do the research here, who do the investigation here, we receive the protocol, a budget, we do the work, and typically that is it,” said Henry Mugerwa, the principal investigator for JCRC. “I was happy to see the Gates MRI team involving us as much as possible, to a point where they see us as part of the publication of results, and us as authors, and being part of the presentation of these results at conferences. That is something I haven’t seen in a long time, if ever. It shows that there is a true partnership.”

About The Authors:

Catherine Correia, Scott Miller, and Grace Fitzgerald oversaw the Gates MRI Phase 1 clinical trial evaluating the safety and PK/PD profile of the experimental monoclonal antibody MAM01 at two sites in Uganda.