E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children born with congenital CMV infection may develop sequelae on follow-up, particularly sensorineural hearing loss. A recent systematic review reports that 13.5% of babies with congenital CMV infection develop sensorineural hearing loss on follow-up. Of babies who develop sensorineural hearing loss, more than a quarter of babies born with symptomatic congenital CMV disease and almost 40% of babies born with asymptomatic CMV infection will have delayed-onset hearing loss. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040016 |
E.1.2 | Term | Sensorineural hearing loss |
E.1.2 | System Organ Class | 100000004854 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040017 |
E.1.2 | Term | Sensorineural hearing loss of combined types |
E.1.2 | System Organ Class | 100000004854 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040018 |
E.1.2 | Term | Sensorineural hearing loss, unspecified |
E.1.2 | System Organ Class | 100000004854 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040015 |
E.1.2 | Term | Sensorineural deafness |
E.1.2 | System Organ Class | 100000004854 |
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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 |
The primary objective is to assess whether a six week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss. This will be accomplished by evaluating changes in hearing in either ear at 6 months from baseline. |
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E.2.2 | Secondary objectives of the trial |
To define the following responses as a function of systemic exposure to ganciclovir (active metabolite of valganciclovir): o CMV viral load in blood o CMV viral load in urine o CMV viral load in saliva To define the safety and tolerability of valganciclovir in enrolled subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject Inclusion Criteria •Signed informed consent from parent(s) or legal guardian(s) •Sensorineural hearing loss (≥ 21dB in one or both ears, documented within 12 weeks prior to study entry) •Children from 1 month up to their 4th birthday •CMV shedding in urine by PCR or culture (including shell vial) within 12 weeks prior to study enrollment |
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E.4 | Principal exclusion criteria |
Subject Exclusion Criteria •Imminent demise •Profound sensorineural hearing loss (> 90dB) in both ears •Patients receiving other antiviral agents or immune globulin •Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis) •Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment •Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir •Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry). •Current receipt of other investigational drugs •Previous receipt of ganciclovir or valganciclovir •Known hypersensitivity to ganciclovir, valganciclovir, or components of the product •Inability to attend follow-up hearing and clinical assessments •Infants with Auditory neuropathy/dyssynchrony. •Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis). Exclusion of each of these conditions is not required for trial enrollment.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in total ear hearing assessments (improved + no change versus other) between Baseline and Study Month 6
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Between Baseline and Study Month 6 |
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E.5.2 | Secondary end point(s) |
1. Change in best ear hearing assessments [improved + no change (normal to normal) versus other; and worse versus other] between Baseline and Study Month 6 2. Change in total ear hearing assessments (improved versus other) between Baseline and Study Month 6 3. Detection of viruria by PCR six weeks and six months after trial entry 4. The quantitative log reduction in viruria detected after 6 weeks of therapy 5. Detection of viremia by PCR six weeks and six months after trial entry 6. The quantitative log reduction in viremia detected after 6 weeks of therapy 7. Detection of CMV in saliva by PCR six weeks and six months after trial entry 8. The quantitative log reduction in CMV viral load in saliva detected after 6 weeks of therapy 9. Correlation of change in viral load with change in total ear and best ear hearing at 6 months 10. Incidence of unanticipated medically attended visits occurring from Study Day 1 through two weeks following the last dose of study drug 11. Incidence of adverse events which lead to permanent discontinuation of valganciclovir therapy or have an unresolved outcome
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Between Baseline and six months. |
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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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Last visit of the last subject |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 5 |