StudyFinder
Search Results Within Category "Audiology/Hearing Loss"
6 Study Matches
Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
Alexandra Sestito - alexandra.sestito@cchmc.org
ALL
PHASE1
NCT05821959
Criteria for Inclusion:
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial
COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device, COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
Sensorineural Hearing Loss, Bilateral
Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural
A Study to Learn More About How Well Finerenone Works, How Safe it is, and How it Moves Into, Through, and Out of the Body Compared to Placebo When Taken With Standard Treatment in Children With Heart Failure and Left Ventricular Systolic Dysfunction (FIORE)
Elise Pickering - Elise.Pickering@cchmc.org
ALL
6 months to 17 years old
PHASE3
NCT07188805
Inclusion Criteria:
* Participants must be 6 months to \<18 years old at the time when the informed consent/assent is signed.
* Left ventricular systolic dysfunction (LVSD) with left ventricular ejection fraction (LVEF) ≤ 50% at screening assessed by echocardiography.
* Elevated NT-pro BNP levels
* \>500 ng/l for children ≥ 6 months to \< 2 years of age
* \>300 ng/l, for children ≥ 2 years to \<18 years
* Heart failure etiologies including congenital heart defects (CHD) with biventricular physiology and systemic LV; idiopathic cardiomyopathy (CM); familial/inherited and/or genetic CM; history of myocarditis (diagnosis of an acute episode was at least 3 months prior to randomization); neuromuscular disorder (eg, duchenne muscular dystrophy); inborn error of metabolism; mitochondrial disorder; acquired (chemotherapy, iatrogenic, infection, rheumatic, or nutritional); ischemic (eg, Kawasaki disease and postoperative heart failure \[HF\]); LV noncompaction.
* Receiving standard of care (SoC) treatment for heart failure according to local guidelines or investigator´s discretion and being on a stable regimen for 30 days prior to randomization.
* Study participants must have a body weight ≥ 4.0 kg at Visit 1.
Exclusion Criteria:
* Serum potassium:
* \> 5.0 mmol/L for children ≥ 2 years of age at either screening or randomization visit
* \> 5.3 mmol/L for children ≥ 6 months to \< 2 years of age at either screening or randomization visit (if estimated glomerular filtration rate \[eGFR\] \< 60 mL/min/1.73m², threshold of \> 5.0 mmol/L will be used)
* Severe renal dysfunction with eGFR \< 30 ml/min/1.73m² at screening or randomization visit.
* Systolic blood pressure (SBP) \< 5th percentile for age, sex and height at screening or randomization.
* Sustained or symptomatic arrhythmias not controlled by drug or device therapy within 30 days prior to randomization.
* Treatment with a mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone) within 30 days of randomization.
* Requirement of any intravenous (IV) vasoactive agents, mechanical ventilation, mechanical circulatory support within 30 days prior to randomization.
* Recent surgical procedure or other intervention to correct or palliate CHD within 3 months prior to randomization or anticipated to undergo cardiac surgery during the 3 months after randomization. DRUG: Finerenone (Kerendia, BAY94-8862), DRUG: Placebo
Left Ventricular Systolic Dysfunction, Heart Failure (Pediatric)
A Study to Learn More About How Safe Finerenone is, When it is Taken for a Longer Time With Standard Treatment, in Children and Young Adults With Heart Failure and Left Ventricular Systolic Dysfunction (FIORELLO)
Elise Pickering - elise.pickering@cchmc.org
ALL
Up to 18 years old
PHASE3
NCT07192952
Inclusion Criteria:
* For participants rolling over from randomized controlled trial (RCT): Prior participation in the finerenone Phase 3 study FIORE (21466) and not permanently discontinued from the study intervention prior to the end of treatment (EoT) visit in FIORE.
* For newly enrolled infants \<6 months of age: Left ventricular systolic dysfunction (LVSD) with left ventricular ejection fraction (LVEF) ≤ 50% at screening assessed by echocardiography.
* For newly enrolled infants \<6 months of age: Elevated NT-pro BNP levels (\> 500 mg/L) at screening.
* For newly enrolled infants \<6 months of age: Heart failure (HF) etiologies include congenital heart defects (CHD) with biventricular physiology and systemic LV; idiopathic cardiomyopathy (CM); familial/inherited and/or genetic CM; history of myocarditis (diagnosis of an acute episode at least 3 months prior to treatment assignment); neuromuscular disorder; inborn error of metabolism; mitochondrial disorder; acquired (chemotherapy, iatrogenic, infection, rheumatic, or nutritional); ischemic (e.g., Kawasaki disease and postoperative HF); LV noncompaction.
* For newly enrolled infants \<6 months of age: Receiving standard of care (SoC) treatment for heart failure according to local guidelines or investigator´s discretion (on a stable regimen for 30 days before baseline).
* Newly enrolled newborns and infants \< 6 months of age must have a body weight of ≥3 kg at Visit 1.
Exclusion Criteria:
* For participants rolling over from randomized controlled trial (RCT): To roll-over to FIORELLO, all participants: Potassium (K+) \>5.5 mmol/L. After unblinding:
* For participants who received finerenone in FIORE: K+ \>5.5 mmol/ L
* For participants who received placebo in FIORE: K+ \>5.0 mmol/L for children ≥2 years of age, and \>5.3 mmol/L for children \<2 years of age (if eGFR is \<60 mL/min/1.73m² for participants \<2 years of age, the serum potassium threshold of \>5.0 mmol/L will be used for exclusion)
* For newly enrolled newborns and infants \< 6 months of age: Potassium ≥ 5.3 mmol/l (if eGFR is \<60 mL/min/1.73m², the serum potassium threshold of \>5.0 mmol/L will be used for exclusion).
* For participants rolling over from RCT: Severe renal dysfunction with estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m² at FIORE EoT or Visit 1.
* For newly enrolled infants \< 6 months of age: Severe renal dysfunction with eGFR \< 30 ml/min/1.73m2 at screening or Visit 1.
* Treatment with a mineralocorticoid receptor antagonist, other than the study intervention, (e.g., spironolactone, eplerenone) within 30 days of Visit 1.
* Requirement of any intravenous (IV) vasoactive agents; mechanical ventilation; mechanical circulatory support; sustained or symptomatic arrhythmias not controlled by drug or device therapy within 30 days prior to study treatment. DRUG: Finerenone (Kerendia, BAY94-8862)
Left Ventricular Systolic Dysfunction, Heart Failure (Pediatric)
A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants, Adolescents and Adults With Hearing Loss Due to Otoferlin Mutations (CHORD)
John Greinwald, Jr. - john.greinwald@cchmc.edu
ALL
PHASE1
NCT05788536
Key
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
Inclusion Criteria:
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
Exclusion Criteria:
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
GENETIC: DB-OTO
Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
DB-OTO, Gene Therapy, Congenital Hearing Loss, Sensorineural Hearing Loss, Auditory Neuropathy, Pediatric, Cochlear Implant, Otoferlin, Deaf, Hard of hearing, Hearing impaired, Hearing disorder, Fully implantable hearing aid, Child, Infant, Adolescents, Young Adults, Adults, CHORD
Otoferlin Gene-mediated Hearing Loss Natural History Study
Elizabeth Dolgas - Elizabeth.Dolgas@cchmc.org
ALL
Up to 44 years old
NCT05572073
Inclusion Criteria:
• Clinical presentation of bilateral sensorineural hearing loss (SNHL), including auditory neuropathy (AN) / auditory neuropathy spectrum disorder (ANSD) phenotype or medical history of AN / ANSD phenotype earlier in life
• Mutation(s) in the otoferlin gene
• Able and willing to comply with all study requirements, as evidenced by successful completion of the informed consent (and assent, if applicable) process Additional Criteria for Inclusion in the Prospective Phase:
• Presence of OAE / CM and absent / abnormal ABRs in at least one ear (that does not have a cochlear implant) within 12 months prior to or at the Month 0 visit
Exclusion Criteria:
• Unwillingness or inability of the potential participant and/or legally authorized representative to comply with all protocol requirements
• Presence of cochlear nerve deficiency and/or cochlear nerve dysplasia Additional Criteria for Exclusion from the Prospective Phase:
• Presence of bilateral cochlear implants at the time of record review or planned within the next 6 months
• Presence of middle ear or auditory brainstem implant(s) at the time of record review or planned within the next 6 months
• Any condition that would not allow the potential participant to complete follow-up assessments during the course of the study and/or, in the opinion of the Investigator, makes the potential participant unsuitable for the study Note: Potential participants will not be excluded based on their sex, gender, race, or ethnicity
OTHER: Natural History Study
Sensorineural Hearing Loss, Bilateral
Otoferlin Gene, sensorineural hearing loss (SNHL), auditory neuropathy, auditory neuropathy spectrum disorder
Heart Institute Biobank & Registry for Adult Congenital Heart Disease and Related Disorders (HIBR-ACHD)
Olivia Croweak - 0livia.croweak@cchmc.org
ALL
16 years and over
NCT07477197
Inclusion Criteria:
• Any person ≥ 16 years-old suspected of having or diagnosed with congenital heart disease (CHD), other cardiovascular disease (CVD), pulmonary hypertension, connective tissue disease, or genetic syndrome/diagnosis.
• Additionally, a cohort (Control group A) of control subjects will be enrolled, again ≥16 years-old, self-reported non-smokers without a known history of diabetes mellitus, myocardial infarction, stroke, heart failure, or chronic kidney disease. These controls will be either:
• A family member or other person accompanying a patient to a clinical encounter; or,
• A volunteer recruited via an advertisement; or,
• Another person who volunteers to enroll in HIBR-ACHD.
• A cohort (Control group B) of comparison subjects who do not have CHD, but have a diagnosis of heart failure or pulmonary hypertension.
Exclusion Criteria:
* Unable to provide informed consent/assent personally or via a legal guardian.
* Considered unsafe to collect the biospecimen determined by either a clinical provider or an HIBR-ACHD investigator.
* Overnight hospitalization for non-obstetric reason with discharge in the prior 30 days. Adult Congenital Heart Disease, Pulmonary Hypertension, Connective Tissue Disease, Other Cardiovascular Conditions
ACHD, Adult Congenital Heart Disease