Extreme pregnancy sickness famously plagued The Princess of Wales and affects approximately 1 in every 100 pregnant women in Australia.
There are currently no therapies that target the root cause of severe nausea and vomiting during pregnancy or hyperemesis gravidarum (HG). The underlying hormonal cause of the condition, identified as GFD15, is likely the reason why many women still have persisting symptoms despite currently available treatments.
A new medication called NGM120 has been developed to target the cause of HG. It has previously been tested in healthy patients and those undergoing chemotherapy to evaluate the safety and efficacy.
It is now going to be tested on pregnant women diagnosed with HG via a commercially sponsored trial, Emerald.
The trial is looking to recruit women with HG aged between 18 and 45 years and between 9 and 16 weeks + 6 days of gestation, with a Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score of 12 or more.
For this first-in-pregnancy trial, the team is looking to enrol 30 women at 11 sites in Australia, the UK, and the Philippines.
Monash Health is the only participating health service in Victoria.
‘We are fortunate to offer the trial to pregnant women in Victoria and hopefully provide some relief from their HG symptoms,’ said Principal Investigator, Professor Kirsten Palmer.
What is hyperemesis gravidarum?
HG is a serious condition that causes severe nausea and vomiting during pregnancy. It is characterised by persistent, often intractable nausea and vomiting, which leads to dehydration, electrolyte and nutritional deficiencies, weight loss and often requires multiple hospital admissions.
HG can also significantly impact a woman’s emotional health, leading to depression, anxiety and a reduced quality of life.
‘HG can severely impact a woman’s physical and emotional well-being, contributing to prolonged hospitalisation, preterm birth, pregnancy termination, post-traumatic stress disorder and decisions for no future pregnancies,’ said Prof Palmer, who is also Head of Maternal Fetal Medicine at Monash Medical Centre.
What is the current treatment?
Current treatments may partially alleviate symptoms such as nausea and vomiting. However, intravenous fluids with electrolytes and vitamins are also often required to treat dehydration, correct electrolyte imbalances, and prevent nutrient deficiencies. Less commonly, additional nutritional support is also needed.
‘Research in this space is needed to safely test promising new treatments to see if they can help pregnant women suffering from HG to feel better. This is where the Emerald study comes in,’ said Prof Palmer.
Phase 1 and Phase 2 trials
A Phase 1 trial assessed the safety and efficacy of the NGM120 drug. The trial was performed in healthy adults to ensure the drug was well tolerated before it was then tested in a population experiencing nausea and vomiting.
In Phase 2, different doses of the drug were administered to non-pregnant patients undergoing chemotherapy to target nausea and vomiting symptoms to find the optimal drug dose.
These trials, in addition to extensive preclinical animal studies, informed the current phase 2 trial design for treating HG in pregnancy trials.
This trial is now recruiting pregnant women between 9 to 16+6 weeks’ gestation with HG.
‘Women are randomised to receive trial treatment with NGM120 at either day 1 or day 8 of trial participation, but all participants will have the opportunity to potentially benefit from the treatment.
‘Ongoing follow-up occurs across the remainder of pregnancy to continue to assess maternal, fetal and neonatal wellbeing,’ Prof Palmer said.
Challenges
Prof Palmer anticipates challenges in recruiting enough pregnant women as HG is not a very common condition.
Despite this, she said her team is committed to offering the trial to all eligible participants identified and continuing to check in with them throughout the pregnancy and postpartum periods to ensure a positive trial experience.
How significant is this study?
If this trial can successfully show that the NGM120 drug alleviates symptoms of HG, this would be the first targeted treatment for women suffering from intractable nausea and vomiting in pregnancy ever.
‘There is a desperate need for new HG treatments and so we are hopeful that by participating in a world-first trial like this, we may help discover if this new drug can afford some benefit – not just to the current trial participants, but to all pregnant people with the most severe forms of nausea and vomiting that current treatments cannot mitigate,’ Prof Palmer said.