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This is a phase 1/2 study of FX-322 at two dose levels compared to placebo in male and female adults otherwise healthy with stable sensorineural hearing loss.
Sensorineural hearing loss (SNHL) accounts for about 90% of all cases of hearing loss. The study will assess the safety of FX-322 (laduviglusib and sodium valproate) given as a single intratympanic injection in subjects with a medical history of sensorineural hearing loss that is associated with noise exposure or sudden hearing loss. Safety will be evaluated both systemically (lab and clinical monitoring) and locally (otoscopy and audiometry) in 24 subjects, and a blood PK profile of FX-322 will also be determined.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FX-322 Low Dose | Experimental | Cohort of 8. Single intratympanic injection |
|
| FX-322 High Dose | Experimental | Cohort of 8. Single intratympanic injection |
|
| Placebo-Low Dose | Placebo Comparator | Cohort of 4. Single intratympanic injection |
|
| Placebo-High Dose | Placebo Comparator | Cohort of 4. Single intratympanic injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FX-322 | Drug | Intratympanic injection of FX-322 consists of laduviglusib and sodium valproate |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Event(s) (TEAEs) | Treatment-emergent adverse events (TEAE) were defined as any untoward medical occurrence in a subject administered study drug that does not necessarily have a causal relationship with the treatment and were collected from the time of first dose through end of study (day 90). In particular, audiometric and otoscopic TEAEs were recorded per the American Speech-Language-Hearing Association (ASHA) guidelines. | Baseline through Day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum concentration (Cmax) of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
| Tmax |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| George Atiee, MD | Worldwide Clinical Trials | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Worldwide Clinical Trials | San Antonio | Texas | 78217 | United States |
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| Label | URL |
|---|---|
| Journal article | View source |
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23 participants were randomized into one of four treatment groups using a 1:1 allocation ratio for dose cohort (approximately 12 in each cohort) and a 2:1 allocation ratio for study drug (approximately 8 FX-322:4 placebo) within each cohort. Subjects received a single dose of FX-322L (0.05mL), FX-322H (0.2mL), or matching placebo.
23 participants who met all inclusion criteria and no exclusion criteria were enrolled at a single clinic site.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo-Low Dose | Single intratympanic injection of placebo into affected ear |
| FG001 | Placebo-High Dose | Single intratympanic injection of placebo into affected ear |
| FG002 | FX-322 Low Dose | Single intratympanic injection of FX-322 (laduviglusib 0.157mg/sodium valproate 4.43mg) into affected ear |
| FG003 | FX-322 High Dose | Single intratympanic injection of FX-322 (laduviglusib 0.628mg/sodium valproate 17.72mg) into affected ear |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo-Low Dose | Single intratympanic injection of placebo into affected ear |
| BG001 | Placebo-High Dose | Single intratympanic injection of placebo into affected ear |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Event(s) (TEAEs) | Treatment-emergent adverse events (TEAE) were defined as any untoward medical occurrence in a subject administered study drug that does not necessarily have a causal relationship with the treatment and were collected from the time of first dose through end of study (day 90). In particular, audiometric and otoscopic TEAEs were recorded per the American Speech-Language-Hearing Association (ASHA) guidelines. | Safety Analysis Set = All subjects exposed to study drug and analyzed according to the actual treatment received regardless of the randomized treatment | Posted | Count of Participants | Participants | Baseline through Day 90 |
|
Baseline through Day 90
Safety Analysis Set = All subjects exposed to study drug and analyzed according to the actual treatment received regardless of the randomized treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo-Low Dose | Single intratympanic injection of placebo into affected ear |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear Discomfort | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carl LeBel, PhD, CDO | Frequency Therapeutics | 781-315-4600 | clinicaltrialsinformation@frequencytx.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 2, 2018 | Sep 1, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2018 | Sep 1, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006319 | Hearing Loss, Sensorineural |
| ID | Term |
|---|---|
| D034381 | Hearing Loss |
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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| Placebo | Drug | Intratympanic injection |
|
Time to reach maximum concentration of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data
| Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
| AUClast | Area under the concentration-time curve of FX-322 (Laduviglusib and Sodium Valproate) from time zero to the time of the last quantifiable concentration, calculated using the linear trapezoidal rule | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
| t1/2 | The observed terminal elimination half-life of FX-322 (Laduviglusib and Sodium Valproate) | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
| CL/F | Apparent total body clearance after extravascular administration of FX-322 (Laduviglusib and Sodium Valproate) | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
| BG002 | FX-322 Low Dose | Single intratympanic injection of FX-322 (laduviglusib 0.157mg/sodium valproate 4.43mg) into affected ear |
| BG003 | FX-322 High Dose | Single intratympanic injection of FX-322 (laduviglusib 0.628mg/sodium valproate 17.72mg) into affected ear |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Placebo-High Dose |
Single intratympanic injection of placebo into affected ear |
| OG002 | Pooled Placebo | All participants receiving placebo |
| OG003 | FX-322 Low Dose | Single intratympanic injection of FX-322 (laduviglusib 0.157mg/sodium valproate 4.43mg) into affected ear |
| OG004 | FX-322 High Dose | Single intratympanic injection of FX-322 (laduviglusib 0.628mg/sodium valproate 17.72mg) into affected ear |
|
|
| Secondary | Cmax | Maximum concentration (Cmax) of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data | Pharmacokinetic Analysis Set = All subjects in the Safety Analysis Set with measurable plasma concentrations | Posted | Mean | Standard Deviation | ng/mL | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
|
|
|
| Secondary | Tmax | Time to reach maximum concentration of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data | Pharmacokinetic Analysis Set = All subjects in the Safety Analysis Set with measurable plasma concentrations | Posted | Mean | Standard Deviation | hr | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
|
|
|
| Secondary | AUClast | Area under the concentration-time curve of FX-322 (Laduviglusib and Sodium Valproate) from time zero to the time of the last quantifiable concentration, calculated using the linear trapezoidal rule | Pharmacokinetic Analysis Set = All subjects in the Safety Analysis Set with measurable plasma concentrations | Posted | Mean | Standard Deviation | ng*hr/mL | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
|
|
|
| Secondary | t1/2 | The observed terminal elimination half-life of FX-322 (Laduviglusib and Sodium Valproate) | Pharmacokinetic Analysis Set = Subjects in the Safety Analysis Set with plasma concentrations above the limit of quantification. Concentration-time data below the limit of quantification (BLQ) were treated as zero. The values of 4 of 7 subjects in the low dose group and 2 of 8 subjects in the high dose group were BLQ and were thus excluded from the PAS for t1/2 as those values could not be calculated. The number analyzed for each data point below reflects quantifiable levels within in each group | Posted | Mean | Standard Deviation | hr | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
|
|
|
| Secondary | CL/F | Apparent total body clearance after extravascular administration of FX-322 (Laduviglusib and Sodium Valproate) | Pharmacokinetic Analysis Set = Subjects in the Safety Analysis Set with plasma concentrations above the limit of quantification. Concentration-time data below the limit of quantification (BLQ) were treated as zero. The values of 4 of 7 subjects in the low dose group and 2 of 8 subjects in the high dose group were BLQ and were thus excluded from the PAS for CL/F as those values could not be calculated. The number analyzed for each data point below reflects quantifiable levels within in each group | Posted | Mean | Standard Deviation | L/hr | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| EG001 | Placebo-High Dose | Single intratympanic injection of placebo into affected ear | 0 | 4 | 0 | 4 | 3 | 4 |
| EG002 | Pooled Placebo | All participants receiving placebo | 0 | 8 | 0 | 8 | 5 | 8 |
| EG003 | FX-322 Low Dose | Single intratympanic injection of FX-322 (laduviglusib 0.157mg/sodium valproate 4.43mg) into affected ear | 0 | 7 | 0 | 7 | 6 | 7 |
| EG004 | FX-322 High Dose | Single intratympanic injection of FX-322 (laduviglusib 0.628mg/sodium valproate 17.72mg) into affected ear | 0 | 8 | 0 | 8 | 7 | 8 |
| Ear Pain | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
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| Ear Pruritus | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
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| Paraesthesia Ear | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
|
| Tympanic Membrace Perforation | Ear and labyrinth disorders | MedDRA v21.0 | Systematic Assessment |
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| Injection Site Pain | General disorders | MedDRA v21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA v21.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA v21.0 | Systematic Assessment |
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| Parosmia | Nervous system disorders | MedDRA v21.0 | Systematic Assessment |
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| Furuncle | Infections and infestations | MedDRA v21.0 | Systematic Assessment |
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| Pulpitis dental | Infections and infestations | MedDRA v21.0 | Systematic Assessment |
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| Viral Infection | Infections and infestations | MedDRA v21.0 | Systematic Assessment |
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| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDRA v21.0 | Systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Systematic Assessment |
|
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA v21.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA v21.0 | Systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | MedDRA v21.0 | Systematic Assessment |
|
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA v21.0 | Systematic Assessment |
|
PIs must obtain sponsor's written consent before publishing or presenting the trial results.
| D012678 |
| Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| t1/2 of sodium valproate |
|
|
| CL/F of sodium valproate |
|
|