E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congenital cytomegalovirus infection.
Sensorineural Hearingloss.
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Congenitale cytomegalovirus infectie.
Sensorineurale Gehoorverlies.
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E.1.1.1 | Medical condition in easily understood language |
Congenital cytomegalovirus infection.
Hearingloss.
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Aangeboren (via de baarmoeder) cytomegalovirus infectie.
Gehoorverlies.
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010420 |
E.1.2 | Term | Congenital CMV infection |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigate whether early valganciclovir treatment of children with SNHL of ≥ 20 dB, unilateral or bilateral, and a confirmed congenital CMV infection can prevent deterioration of the hearing loss at 18-22 months follow-up.
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Onderzoeken of vroege behandeling met valganciclovir bij kinderen met gehoorverlies van ≥ 20 dB, unilateraal of bilateraal, en een congenitale CMV infectie de verergering van het gehoorverlies bij 18-22 maanden follow-up kan tegegaan.
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E.2.2 | Secondary objectives of the trial |
1) Investigate whether early valganciclovir treatment of children with
SNHL of ≥ 20 dB, unilateral or bilateral, and a confirmed congenital CMV infection can prevent cognitive and motor retardation. Communicative and speech development will be extensively assessed.
2) Investigate whether early valganciclovir treatment of children with
SNHL of ≥ 20 dB, unilateral or bilateral, and a confirmed congenital CMV infection reduces the CMV viral load in urine and blood samples during 6 weeks treatment and one week after completion of treatment. At age 18-22 months (follow-up) solely the urine sample will be investigated for the viral load.
3) Investigate whether drug resistance has evolved. |
1) Onderzoeken of vroege behandeling met valganciclovir bij kinderen met gehoorverlies van ≥ 20 dB, unilateraal of bilateraal, en een congenitale CMV infectie cognitieve en bewegings retardatie kan
voorkomen. Communicatieve en spraak ontwikkeling worden getest bij 18-22 maanden leeftijd follow-up.
2) Onderzoeken of vroege behandeling met valganciclovir bij kinderen met gehoorverlies van ≥ 20 dB, unilateraal of bilateraal, en een congenitale CMV infectie de CMV virale load zal verlagen in urine en
bloed dat wekelijks wordt afgenomen gedurende de 7 weken na inclusie, en bij 18-22 maanden. Bij 18-22 maanden zal alleen urine worden afgenomen.
3) Eventuele medicatie resistentie onderzoeken. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Treatment group and refusal control group
- Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both ears).
- Age at time of inclusion is ≤ 12 weeks after birth.
- Born at ≥ 37 weeks gestational age.
- Birth weight ≥ 2500 gram.
- Parental signed informed consent.
Historical control group
- Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both ears).
- Age at time of inclusion is > 13 weeks after birth.
- Born at ≥ 37 weeks gestational age.
- Birth weight ≥ 2500 gram.
- Parental signed informed consent. |
Behandel groep en weiger controle groep:
- Kinderen met congenitaal CMV en gehoorverlies (≥ 20 dB unilateraal of bilateraal)
- Leeftijd bij inclusie ≤ 12 weken.
- Geboorte bij ≥ 37 weken na conceptie.
- Geboorte gewicht ≥ 2500 gram.
- Toestemmingsverklaring door ouders ondertekend.
Historische controle groep:
- Kinderen met congenitaal CMV en gehoorverlies (≥ 20 dB, unilateraal of bilateraal).
- Leeftijd bij inclusie > 13 weken na geboorte.
- Geboren bij ≥ 37 na conceptie.
- Geboorte gewicht ≥ 2500 gram.
- Toestemmingsverklaring door ouders ondertekend. |
|
E.4 | Principal exclusion criteria |
Treatment group and refusal control group
- Previously noted (≤ 12 weeks after birth) symptoms possibly related to congenital CMV, for which medical attention was requested. For example: intra uterine growth retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly, thrombocytopenia, elevated transaminases, elevated bilirubin.
- Treatment with other antiviral agents or immunoglobulins.
- Solely applicable for treatment group: leucopenia < 0,5 x 10*9/L (blood sample tested at t=0).
Historical control group
- Previously encountered (≤ 12 weeks after birth) symptoms possibly related to congenital CMV, for which medical attention was requested For example: intra uterine growth retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly, thrombocytopenia, elevated transaminases, elevated bilirubin.
- Treatment with (val)ganciclovir.
- Treatment with other antiviral agents or immunoglobulins. |
Behandel groep en weiger controle groep:
- Eerder gevonden (≤ 12 weken na geboorte) symptomen mogelijk passend bij congenitaal CMV, waarvoor medische zorg werd gezocht. Bijvoorbeeld: intra uteriene groei achterstand, petechieen, hepatosplenomegalie, icterus, microcephalie, thrombocytopenie, verhoogde transaminasen, hyperbilirubine.
- Behandeling met andere antivirale medicatie of immunoglobulines.
- Voor behandel groep: leukopenie < 0,5 x 10*9/L (bloed getest bij t=0).
Historische controle groep:
- Eerder gevonden (≤ 12 weken na geboorte) symptomen mogelijk passend bij congenitaal CMV, waarvoor medische zorg werd gezocht. Bijvoorbeeld: intra uteriene groei achterstand, petechieen, hepatosplenomegalie, icterus, microcephalie, thrombocytopenie, verhoogde transaminasen, hyperbilirubine.
- Behandeling met (val)ganciclovir.
- Behandeling met ander antivirale medicatie of immunoglobulines. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the status of the sensorineural hearing loss expressed in dB, in children with congenital CMV at age 18-22 months follow-up. |
Sensorineural gehoorverlies (in dB), bij kinderen met congenitaal CMV bij leeftijd 18-22 maanden. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Hearing loss will be evaluated at age 18-22 months. |
Gehoorverlies wordt bepaald bij leeftijd 18-22 maanden. |
|
E.5.2 | Secondary end point(s) |
The secondary endpoint is the development of the infants.
The tertiary endpoint is the viral load (in dried blood spots,blood and urine) during 7 weeks after inclusion and at age 18-22 months follow-up (for infants in the treatment and refusal control group). For infants in the historical control group materials collected previously will be tested when available.
The final endpoint is the possibility of development of drug resistance. |
Secundaire eindpunt is de ontwikkeling van de kinderen.
Tertiaire eindpunt is de virale load (in dried blood spot, bloed en urine) gedurende de 7 weken na inclusie en bij 18-22 maanden follow-up (voor kinderen in de behandel en weiger controle groep). Voor kinderen in de historische controle groep zullen deze materialen ook worden getest indien beschikbaar.
Als laatste eindpunt wordt eventuele medicatie resistentie onderzocht. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The development of the infants will be tested at age 18-22 months follow-up.
For treated infants and infants in the refusal control group the viral load will be determined at inclusion and weekly in urine during
the first 7 weeks after inclusion (total 8 moments). For treated infants it will be determined at inclusion and weekly in blood samples (total 8 moments). For untreated infants it will be determined twice in blood (at inclusion and in week 6). At age 18-22 months follow-up the viral load will be determined in urine for all infants (also the infants in the historical control group).
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De ontwikkeling van de kinderen wordt bij leeftijd 18-22 maanden follow-up onderzocht.
De behandelde kinderen en kinderen in de weiger controle groep wordt de virale load bij inclusie en daarna wekelijks gedurende de 7 weken na inclusie bepaald (totaal 8 momenten). Voor behandelde kinderen wordt bij inclusie en daar wekelijks gedurende de behandeling de virale load in bloed bepaald (totaal 8 momenten). Voor onbehandelde kinderen wordt de virale load in bloed tweemaal bepaald (inclusie en in week 6). Bij leeftijd 18-22 maanden wordt voor alle kinderen de virale load in urine bepaald (ook voor kinderen in de historische controle groep). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Reguliere behandeling |
Regular care |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The last visit of the last subject. |
Het laatste bezoek van de laatste proefpersoon. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |