Ignite Creation Date:
2024-05-06 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 1:55 PM
Study NCT ID:
NCT04732260
Status:
COMPLETED
Last Update Posted:
2022-03-15
First Post:
2021-01-24
Brief Title:
Prenatal Treatment of Congenital Cytomegalovirus Infection With Letermovir Randomized Against Valaciclovir - STEP 1 CYMEVAL3-STEP1
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Prenatal Treatment of Congenital Cytomegalovirus Infection With Letermovir Randomized Against Valaciclovir - STEP 1
Status:
COMPLETED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CYMEVAL3-STEP1
Brief Summary:
In the model of the perfused cotyledon Letermovir crosses the placenta to reach appropriate fetal concentration The cotyledon model can only be performed in the third trimester placenta Although it is probable that the transplacental passage in the second trimester is in the same range than the one found in the 2th trimester it needs to be confirmed The study will be divided in 2 steps step 1 will study the Letermovir transplacental transfer in the second trimester and step 2 will test the efficacy of letermovir to inhibit replication in infected fetuses
Main objective To measure the Letermovir transplacental transfer in the second trimester and its accumulation in the amniotic fluid and the placenta in the second trimester
Primary end point
Concentrations reached in fetal blood relative to EC50 of letermovir
Main objective To measure the Letermovir transplacental transfer in the second trimester and its accumulation in the amniotic fluid and the placenta in the second trimester
Primary end point
Concentrations reached in fetal blood relative to EC50 of letermovir
Detailed Description:
The eligible population of step 1 will be pregnant women in their second trimester of pregnancy and undergoing TOP for any fetal abnormality and no evidence of placental dysfunction
Letermovir LTM is a new anti CMV drug manufactured by Merck that
is highly efficient in vitro against CMV more than ganciclovir the gold standard drug
is as efficient as valganciclovir to cure CMV infection and highly efficient as a prophylaxis to avoid CMV infection and disease in bone marrow transplated patients
is very well tolerated
has no data from the use in pregnant women and animal studies are insufficient with respect to fetotoxicity but no specific concern in pregnant women arises from its safety profile
crosses the placenta in the ex vivo model of the human perfused cotyledon to reach efficient fetal concentration
In this STEP 1 study we elected to test 2 Letermovir dosages
240 mg given orally once a day Based on 10 rate of letermovir transplacental passage as demonstrated in the cotyledonon model we calculated that the dosage of 240 mg given once a day to the pregnant woman should be suffisent to reach efficient concentration in fetal blood
480 mg day given orally once a day 480 mg per day is the recommended dose to prevent CMV infection in bone marrow transplanted patients
The risks added by the study are those of letermovir nausea diarrhea and vomiting frequent hypersensitivity loss of appetite headache vertigo abdominal pain ALT and AST increase muscule spasm blood creatinine increase fatigue peripheral edema very rare The expected benefit for the women is none
Women and obstetrician investigator will sign the written consent for the trial
Validation of inclusion and non-inclusion criteria will be assessed by the obstetrician investigator as follows
age weight height and medical history will be collected
Inquiry on maternal concomitant treatments
Blood sampling 4 ml altogether
1 Heparinate Lithium tube 2 ml for measurements of urea creatinine creatinine clearance liver enzyme ALAT ASAT GGT PAL bilirubine
1 EDTA tube of 2 ml for full blood test count These measurements will be done in the biochemistry laboratory of the investigating site
When validation of inclusion and non-inclusion criteria is done all the criteria will be available on the day of the baseline visit the woman receives the tablets of letermovir They will be allocated either 240 mg or 480 mg up until termination of pregnancy 5 women will receive 240 mg In order to have variation in the time elapsed between administration and sampling it will be asked to 3 women to take the drug every morning and to 2 patients to take the drug every evening 5 women will receive 480 mg This time it will be asked to 2 women to take the drug every morning and to 3 patients to take the drug every evening
Hence the day of TOP patients who take the drug every evening will have the largest delay between the last intake and blood sampling The patients who take the drug every morning should take the last tablet early in the morning the day of TOP and latest 4 hours before the blood sampling
After the baseline visit there will be one other visit just before TOP the obstetrician investigator will be in charge of this visit
1 Maternal examination will comprise
Inquiry of potential side effects nausea vomiting diarrhea rash cough peripheral edema headache abdominal pain decrease appetite others
SAEAE will be collected
Blood pressure measurement
Blood sampling 5 ml with one Lithium Heparinate tube for letermovir dosage
1 Heparinate Lithium tube 2 ml for measurements of urea creatinine creatinine clearance liver enzyme ALAT ASAT GGT PAL bilirubine
Hours of the 3 intakes of pills will be recorded in an individual treatment booklet
2 At TOP fetal examination will comprise
Fetal blood sampling 5 ml in a Lithium Heparinate tube for Letermovir dosage collected at the time of feticide before lethal injection is given in the umbilical vein under ultrasound guidance
Amniotic fluid sampling 5 ml on Lithium heparinate tube for Letermovir dosage collected by the midwife at the time of artificial rupture of the amniotic membranes
Placental biopsies sampling 2 cotyledons for Letermovir dosage collected after delivery
SAEAE will be collected
3 At day 4 after TOP
Phone call to collect SAEAE after TOP
The duration of participation of each woman including data collection will be a maximum of 7 days 3 days before the TOP and 4 days after TOP
The duration of the study will be 9 months
Letermovir LTM is a new anti CMV drug manufactured by Merck that
is highly efficient in vitro against CMV more than ganciclovir the gold standard drug
is as efficient as valganciclovir to cure CMV infection and highly efficient as a prophylaxis to avoid CMV infection and disease in bone marrow transplated patients
is very well tolerated
has no data from the use in pregnant women and animal studies are insufficient with respect to fetotoxicity but no specific concern in pregnant women arises from its safety profile
crosses the placenta in the ex vivo model of the human perfused cotyledon to reach efficient fetal concentration
In this STEP 1 study we elected to test 2 Letermovir dosages
240 mg given orally once a day Based on 10 rate of letermovir transplacental passage as demonstrated in the cotyledonon model we calculated that the dosage of 240 mg given once a day to the pregnant woman should be suffisent to reach efficient concentration in fetal blood
480 mg day given orally once a day 480 mg per day is the recommended dose to prevent CMV infection in bone marrow transplanted patients
The risks added by the study are those of letermovir nausea diarrhea and vomiting frequent hypersensitivity loss of appetite headache vertigo abdominal pain ALT and AST increase muscule spasm blood creatinine increase fatigue peripheral edema very rare The expected benefit for the women is none
Women and obstetrician investigator will sign the written consent for the trial
Validation of inclusion and non-inclusion criteria will be assessed by the obstetrician investigator as follows
age weight height and medical history will be collected
Inquiry on maternal concomitant treatments
Blood sampling 4 ml altogether
1 Heparinate Lithium tube 2 ml for measurements of urea creatinine creatinine clearance liver enzyme ALAT ASAT GGT PAL bilirubine
1 EDTA tube of 2 ml for full blood test count These measurements will be done in the biochemistry laboratory of the investigating site
When validation of inclusion and non-inclusion criteria is done all the criteria will be available on the day of the baseline visit the woman receives the tablets of letermovir They will be allocated either 240 mg or 480 mg up until termination of pregnancy 5 women will receive 240 mg In order to have variation in the time elapsed between administration and sampling it will be asked to 3 women to take the drug every morning and to 2 patients to take the drug every evening 5 women will receive 480 mg This time it will be asked to 2 women to take the drug every morning and to 3 patients to take the drug every evening
Hence the day of TOP patients who take the drug every evening will have the largest delay between the last intake and blood sampling The patients who take the drug every morning should take the last tablet early in the morning the day of TOP and latest 4 hours before the blood sampling
After the baseline visit there will be one other visit just before TOP the obstetrician investigator will be in charge of this visit
1 Maternal examination will comprise
Inquiry of potential side effects nausea vomiting diarrhea rash cough peripheral edema headache abdominal pain decrease appetite others
SAEAE will be collected
Blood pressure measurement
Blood sampling 5 ml with one Lithium Heparinate tube for letermovir dosage
1 Heparinate Lithium tube 2 ml for measurements of urea creatinine creatinine clearance liver enzyme ALAT ASAT GGT PAL bilirubine
Hours of the 3 intakes of pills will be recorded in an individual treatment booklet
2 At TOP fetal examination will comprise
Fetal blood sampling 5 ml in a Lithium Heparinate tube for Letermovir dosage collected at the time of feticide before lethal injection is given in the umbilical vein under ultrasound guidance
Amniotic fluid sampling 5 ml on Lithium heparinate tube for Letermovir dosage collected by the midwife at the time of artificial rupture of the amniotic membranes
Placental biopsies sampling 2 cotyledons for Letermovir dosage collected after delivery
SAEAE will be collected
3 At day 4 after TOP
Phone call to collect SAEAE after TOP
The duration of participation of each woman including data collection will be a maximum of 7 days 3 days before the TOP and 4 days after TOP
The duration of the study will be 9 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-002924-35 | EUDRACT_NUMBER | None | None |