A research study testing NGM120 in pregnant women with severe nausea and vomiting (hyperemesis gravidarum)
| ISRCTN | ISRCTN76681798 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76681798 |
| IRAS number | 1010482 |
| Secondary identifying numbers | 120-HG-201, CPMS 63108 |
- Submission date
- 06/09/2024
- Registration date
- 13/12/2024
- Last edited
- 06/02/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
This clinical trial aims to help pregnant women suffering from severe nausea and vomiting, known as hyperemesis gravidarum (HG). HG can lead to significant weight loss, multiple hospital admissions and other pregnancy complications including fetal growth problems and earlier delivery (preterm delivery). Currently, there are limited treatments available for HG. This trial will test NGM120, a monoclonal antibody, to see if it is safe and effective for treating HG.
Who can participate?
Pregnant women aged 18 to 40 years who are experiencing severe nausea and vomiting between 10 and 15 weeks of pregnancy
What does the study involve?
The participants will be divided into two groups, both receiving the standard care of ondansetron, fluids, and vitamins. One group will also receive a single dose of the study drug, NGM120; the other will receive a single dose of placebo. After 7 days, participants will receive a single dose of the other treatment. Researchers will closely monitor the participants to ensure safety and assess the effectiveness of NGM120 in reducing nausea and improving daily functioning. The goal of the study is to better understand how well NGM120 works to treat severe nausea during pregnancy.
What are the possible benefits and risks of participating?
A benefit of participating in the study is that participants’ symptoms of HG may improve; however, this cannot be guaranteed. Being in this study will help doctors learn more about NGM120 and HG. This may help others with HG in the future.
As with any clinical trial, participants may face several risks and burdens, but measures will be taken to minimise them. An independent group of safety experts will regularly review participant safety during the study. They will make recommendations to stop or make changes to the study if their review shows this to be necessary.
One risk faced by participants is the potential side effects from the investigational product, NGM120, which could include nausea, headaches, and other reactions. Procedures such as blood tests, and the study drug/placebo injections may also cause discomfort. However, these risks are necessary to assess the safety and effectiveness of NGM120.
Another risk involves the potential impact on pregnancy, as the study includes pregnant women. Although the trial is designed with safety in mind, there are unknown risks to the foetus or pregnancy complications. Understanding how NGM120 affects pregnant women is essential for developing better treatments for HG. To mitigate these risks, regular health checks for both the mother and baby will be conducted, and NHS sites with expertise in managing high-risk pregnancies will oversee the trial.
Participants will need to stop any current HG treatments during the study, which they may not initially be comfortable with. This step is necessary to accurately evaluate the effectiveness of NGM120 without interference from other treatments. To minimise the impact, participants will still receive supportive care, including ondansetron and fluids, and their symptoms will be closely monitored.
The trial requires 4 hospital visits over 12 days, which could be considered burdensome, especially for those already struggling with severe nausea and vomiting. These visits are crucial for monitoring participants' health and ensuring the study's safety and accuracy. The clinical study team will try to reduce this burden by scheduling visits efficiently.
Finally, there may be concerns about confidentiality and privacy, as sharing personal and medical information in the trial could raise privacy issues. Collecting this data is essential for analysing the effects of NGM120 and ensuring the study's validity. To protect participants, data protection policies and procedures will be followed, and their consent will be obtained before any information is shared. NHS sites involved in the study are experienced in handling sensitive information and will ensure participants' confidentiality is maintained throughout the trial.
This trial has been carefully designed to minimise risks and burdens for participants while aiming to improve treatments for HG. By prioritising safety and support, the study seeks to gather valuable information to benefit women suffering from HG in the future.
Where is the study run from?
Premier Research (UK)
When is the study starting and how long is it expected to run for?
September 2024 to December 2025
Who is funding the study?
NGM Biopharmaceuticals (USA)
Who is the main contact?
EMERALD@ngmbio.com
Contact information
Scientific
NGM Biopharmaceuticals, Inc.
333 Oyster Point Boulevard
South San Francisco
CA 94080
United States of America
| Phone | +1 (0)650 243 5555 |
|---|---|
| EMERALD@ngmbio.com |
Principal Investigator
Colney Lane
Nowich
NR4 7UY
United Kingdom
| Phone | +44 (0)1603286286 |
|---|---|
| JON.LARTEY@nnuh.nhs.uk |
Study information
| Study design | Single-blind randomized placebo-controlled two-group cross-over trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A Phase II randomized, proof-of-concept study to evaluate the safety, tolerability, and efficacy of NGM120 in pregnant women with severe nausea and vomiting (hyperemesis gravidarum) |
| Study acronym | EMERALD |
| Study hypothesis | Primary objective: 1. To assess the safety and tolerability of NGM120 in addition to standard of care (SOC) and supportive care. Secondary objectives: 1. To evaluate the efficacy of NGM120 in addition to SOC and supportive care compared to placebo in addition to SOC and supportive care through the use of Pregnancy-Unique Quantification of Emesis 24 (PUQE-24) scores and on HyperEmesis Level Prediction (HELP) scores |
| Ethics approval(s) |
Approved 22/11/2024, North East - Tyne & Wear South Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)2071048120, +44 (0)207 104 8286, +44 (0)2071048108; tyneandwearsouth.rec@hra.nhs.uk), ref: 24/NE/0177 |
| Condition | Hyperemesis gravidarum |
| Intervention | The study drug is NGM120, a humanized monoclonal antibody. Participants will be randomized to receive a single dose of NGM120 or placebo (a sterile solvent with no NGM120) on Day 1, and cross-over to the other treatment on Day 8, according to the treatment sequence assigned. All participants will be centrally assigned to randomized study treatment using an Interactive Web Response System. As supportive care, participants will receive intravenous (IV) fluids with multivitamins administered on Study Days -3, 1, 5, and 8, regardless of the treatment sequence to which they are assigned. Participants will receive IV multivitamins according to the SOC at each study center. Additionally, participants will receive 4 mg ondansetron three times daily as SOC, administered orally or sublingually. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | NGM120 |
| Primary outcome measure | The safety and tolerability of NGM120 in addition to SOC and supportive care, assessed by the incidence of treatment-emergent adverse events (TEAEs) characterized by type, frequency, severity, timing, seriousness, and relationship to the study drug over time. Specific timepoints for evaluation include Study Day 1, when the initial dose of the investigational product is administered, and continuously through Study Day 12, to monitor any adverse events following treatment. At each scheduled visit or contact, adverse events will be recorded to track their type, frequency, severity, timing, and seriousness, along with their relationship to the study drug. |
| Secondary outcome measures | 1. Nausea, vomiting, and retching assessed using the Pregnancy-Unique Quantification of Emesis 24 score (PUQE-24) at Baseline and Study Day 5 2. Nausea, vomiting, retching, and overall wellbeing assessed using the HyperEmesis Level Prediction (HELP) score at Baseline and Study Day 5 |
| Overall study start date | 04/09/2024 |
| Overall study end date | 12/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 40 Years |
| Sex | Female |
| Target number of participants | 30 |
| Participant inclusion criteria | Current inclusion criteria as of 06/02/2025: 1. Pregnant females with singleton pregnancy and gestational age of the fetus is between 10 to 15 weeks. 2. Severe nausea and vomiting with PUQE-24 greater than or equal to 13 3. Agree to discontinue any current anti-emetics or other treatments for hyperemesis gravidarum and will receive ondansetron and IV fluids per protocol. _____ Previous inclusion criteria: 1. Pregnant females with singleton pregnancy and gestational age of the fetus is between 10 to 15 weeks. 2. Severe nausea and vomiting with PUQE-24 greater than or equal to 13 3. Agree to discontinue any current anti-emetics or other treatments for hyperemesis gravidarum. |
| Participant exclusion criteria | 1. History of cyclic vomiting or gastroparesis which could contribute to the etiology of nausea and vomiting 2. Prior bariatric surgery, bowel obstruction, pancreatitis, or other prior health conditions which could contribute to the etiology of nausea and vomiting 3. Positive for hepatitis B surface antigen, hepatitis C viral load RNA, or anti-human immunodeficiency virus 4. Pre-existing diagnosis of chronic kidney disease, diabetes (type 1 or 2), significant cardiac disease (including long QT syndrome) or epilepsy 5. Elevated liver enzymes (alanine aminotransferase or aspartate aminotransferase greater than or equal to 3.0 times the upper limit of normal) 6. Known fetal chromosomal abnormalities 7. Pregnancy conceived through in vitro fertilization |
| Recruitment start date | 18/12/2024 |
| Recruitment end date | 18/04/2025 |
Locations
Countries of recruitment
- Australia
- England
- United Kingdom
Study participating centres
Birmingham
B4 6NH
United Kingdom
Cambridge
CB2 0SW
United Kingdom
Wakefield
WF1 4DG
United Kingdom
Norwich
NR4 7UY
United Kingdom
Hampstead
London
NW3 2QG
United Kingdom
London
SE5 9RS
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Sponsor information
Industry
333 Oyster Point Boulevard
South San Francisco
CA 94080
United States of America
| Phone | +1 (0)650 243 5555 |
|---|---|
| EMERALD@ngmbio.com |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- NGM Biopharmaceuticals, Inc., NGM Biopharmaceuticals Inc., NGM Biopharmaceuticals Inc, NGM Bio
- Location
- United States of America
Results and Publications
| Intention to publish date | 17/10/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Conference presentation 3. Submission to regulatory authorities 4. Other Before Personal Data is transferred to the Sponsor, the research team will replace any information that could directly identify a patient with a generic code which the Sponsor cannot link to a patient’s identity. Therefore, when results are published, there will be no identifiable data. After completion of the study a clinical trial summary report will be prepared and submitted to the MHRA and REC within 1 year of the end of the trial. (Results from the study will be also posted on the public registers where the trial was originally registered. All publications, presentations and summaries relating to this study must be first approved by the sponsor to ensure that data are presented correctly and that confidential information are not inadvertently disclosed.) |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
06/02/2025: The following changes were made to the trial record:
1. The acronym was added.
2. The inclusion criteria were changed.
20/01/2025: Internal review.
06/09/2024: Study's existence confirmed by the HRA.
