#Denmark #Copenhagen #pretomanid #RR-TB #IMPAACT

Positive Advances in Pediatric Tuberculosis Treatment

At the 2025 Union World Conference on Lung Health held in Copenhagen, the spotlight was on groundbreaking new data from the IMPAACT 2034 study. This late-breaking oral abstract presented compelling evidence regarding the use of pretomanid in young girls suffering from rifampicin-resistant tuberculosis (RR-TB).

A New Hope for Children with RR-TB

In this pioneering study, researchers established that a single dose of pretomanid is not only safe and well-tolerated by pediatric patients but can achieve pharmacokinetic levels comparable to those seen in adults. This is a remarkable step towards making pretomanid-regimens available to children, addressing a significant gap in treating childhood TB.

Pretomanid is classified as a nitroimidazole antibiotic and is commonly used in BPaL (bedaquiline, pretomanid, linezolid) regimens for adults dealing with drug-resistant TB. As health professionals seek to enhance treatment options for children, specially designed 10 mg and 50 mg dispersible tablets were created and tested to ensure these formulations offer similar drug exposure as adult tablets before their application in younger patients.

Study Details and Beyond

The IMPAACT 2034 Phase 1 study involved 28 female children aged between 0.6 to 17.6 years with RR-TB, including 7 participants also living with HIV. The study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) as part of the National Institutes of Health (NIH), took place across South Africa (n=26) and Thailand (n=2).

Participants were categorized based on their weight and received a single dose of pretomanid between 20-200 mg. This design aimed to ensure data accuracy regarding their treatment outcomes. Follow-ups extended for two weeks after dosage to facilitate a robust analysis of the PK (pharmacokinetics) and safety data.

Key Insights from the IMPAACT 2034 Study

The results from this pivotal study are promising:

• - Comparable Drug Exposure: The pharmacokinetic profiles demonstrated that pretomanid exposure in children was similar to that found in both healthy adults and adults with TB across all weight cohorts.
• - Favorable Safety Profile: Notably, a single dose of pretomanid was well tolerated without unexpected safety issues arising in any cohort, reinforcing its suitability for a younger demographic.

These insights are crucial because they mark the first clinical evaluation of pretomanid's pharmacokinetics in children. Dr. Eugene Sun, Senior Vice President of RD at TB Alliance, expressed that the findings play an essential role in guiding future developments for increasing access to pretomanid for pediatric patients battling drug-resistant TB.

An Eye on the Future

The enrollment of male participants was not advised by the U.S. Food and Drug Administration (FDA) due to concerns of potential testicular toxicity observed in male rodents during earlier studies; however, plans are in place to incorporate male children in subsequent trials.

Dr. Sharon Nachman, the Principal Investigator and Chair at the IMPAACT Network, reiterated the necessity of developing MDR-TB specific therapies that cater to children's needs. She emphasized that ensuring children with TB have access to effective and tolerable treatments could significantly enhance their health outcomes and overall quality of life.

With pretomanid receiving approval in the U.S. since 2019 for treatment regimens of highly drug-resistant TB, this latest development adds another layer of validation to its potential in combating childhood TB. The importance of ongoing innovation in this domain cannot be overstated, particularly in light of the widespread drug resistance faced by healthcare providers worldwide.

About the IMPAACT Network and TB Alliance

The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network focuses on improving health outcomes in various vulnerable populations through high-quality clinical research. On the other hand, TB Alliance is dedicated to discovering more efficient and affordable TB regimens, further supporting global health efforts.

As pediatric pretomanid therapies move forward, they symbolize a broader ambition—one that seeks to bridge treatment gaps for children facing the trials of drug-resistant tuberculosis.