POEM Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bethesda Diabetes Research Center B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi · ZonMw · Gemeente Drenthe · Novo nordisk

External identifiers

EU CT number

2024-519386-21-01

EudraCT number

2015-002148-15

ClinicalTrials.gov

NCT02947503

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The central aim is to investigate whether metformin from the start of the diagnosis GDM on top of standard of care may improve the treatment of GDM and related outcomes of mother and child. Metformin is used as a tool to reduce insulin resistance, the underlying cause of GDM. In the POEM study, the effects of metformin on top of standard of care versus standard of care alone in GDM are compared during pregnancy until 6 weeks after delivery (Phase A), from 6 weeks until 1 year after delivery (Phase B) and from 1 until 20 years after delivery (Phase C) with specified objectives reflected by well-defined clinically relevant endpoints.

Conditions and MedDRA coding

Gestational diabetes mellitus

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Pregnant women with GDM defined as a FPG ≥ 5,3 mmol/l and/or an OGTT with a PG ≥ 7,8 mmol/l, two hours after the oral intake of 75 gram glucose 2. Written informed consent 3. Age 18-45 years 4. Gestational age at inclusion 16-34 weeks 5. HbA1c at inclusion ≤ 48 mmol/mol (6.5% Hb)

Exclusion criteria 1

1. 1. Diabetes mellitus before pregnancy, except previous GDM 2. Proteinuria (UACR > 35 mg/mmol) at screening (UTI excluded) 3. Malignancy during the last 5 years before inclusion, except non-melanoma skin cancer 4. Psychiatric and/or mood disorder potentially affecting compliance of treatment 5. Chronic liver disease and/or ASAT and/or ALAT > 3x ULN 6. Chronic renal failure with a GFR < 45 ml/min/1.73m2 7. Chronic pulmonary failure with hypoxia 8. Significantly uncontrolled hypertension – SBP > 160 mm Hg despite medical treatment 9. Chronic treatment with oral corticosteroids 10. Intolerance for metformin and/or earlier use of metformin in this pregnancy 11. Membership of the POEM study group 12. Severe foetal anomaly at inclusion – like major neural tube and/or cardiac malformation 13. Ruptured membranes 14. Multiple pregnancy 15. Bariatric surgery in medical history 16. Hyperemesis gravidarum

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase A: GDM Outcome Score (= GOS), an ordinal variable (range 0-8) per pregnancy: (1) pregnancy related hypertension, including pre-eclampsia and eclampsia, (2) large for gestational age (LGA) at delivery (neonatal weight > 90th percentile), (3) premature delivery (< 37.0 weeks of gestation), (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia (< 2.6 mmol/l), and (8) admission to the NICU.
2. Phase B and Phase C have each three co-primary endpoints: maternal T2D, weight development in the mother, and weight development in the child.

Secondary endpoints 15

1. Phase A: each of these eight endpoints apart is a secondary endpoint.
2. MOS (maternal outcome score): including Caesarean delivery, Pre-eclampsia/eclampsia/HELLP syndrome/gestational hypertension, Maternal mortality, Postpartum haemorrhage, Thrombosis (in pregnancy and/or childbed).
3. NOS (neonatal outcome score): including Infant Respiratory Distress Syndrome (IRDS) needing nasal CPAP, optiflow, mechanical ventilation and/or surfactant replacement, stillbirth and neonatal death, preterm birth = birth before 37.0 weeks, dystocia of the shoulder during delivery, instrumental delivery, caesarean delivery, neonatal hypoglycaemia < 2.6 mmol/l, neonatal jaundice needing phototherapy, admission to NICU, Apgar score as a variable, Apgar score < 7 at 5 minutes, congenital anomaly
4. Maternal weight, weight gain and change in body compostition (impedance)
5. Maternal glycaemic control: FPG and glucose tolerance
6. Maternale proteinuria
7. Maternal insulin rescue and daily dose of insulin after failure of study drug
8. Acceptability of treatment
9. Maternal urinary tract infection
10. Maternal metabolic varibales from venous sampling (please see protocol)
11. Child: intra-uterine measurements by ultra-sonography
12. Child: foetal weight at delivery
13. Neonatal metabolic variables from umbilical cord
14. Phase B/C: Diabetes & Prediabetes development, Weight development, Hypertension development, thrombotic and CVD incidents, development of any chronic disease
15. Phase B/C: Growth and weight development, gonadal and gender development, puberty and maturation, eductional and intellectual development

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bethesda Diabetes Research Center B.V.

Sponsor organisation

Bethesda Diabetes Research Center B.V.

Address

Dr. G.H. Amshoffweg 1

City

Hoogeveen

Postcode

7909 AA

Country

Netherlands

Scientific contact point

Organisation

Bethesda Diabetes Research Center B.V.

Contact name

Adriaan Kooy

Public contact point

Organisation

Bethesda Diabetes Research Center B.V.

Contact name

Adriaan Kooy

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications