SoRbitol Dehydrogenase (SORD) DEficiency MedDRA version: 20.0 Level: LLT Classification code 10029328 Term: Neuropathy System Organ Class: 100000004852
Conditions
Interventions
Product Name: Govorestat
Product Code: AT-007
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Govorestat
CAS Number: 2170729-29-8
Current Sponsor code: AT-007
Other descriptive name: S292
Co
Sponsors
Applied Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures. Consent for minor patients (until the age of 18) must provided by parents or legal representatives. 2. Male and non-pregnant, non-lactating female patients between the ages of 16 and 55 years, inclusive. 3. Females must be of non-childbearing potential (defined as surgically sterile [i.e., had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy =6 months prior to the first dose of study drug] or postmenopausal for =1 year [confirmatory follicle-stimulating hormone or FSH test results required] prior to the first dose of study drug) or agree to use a highly effective form of birth control from Screening until 15 days (5 half-lives) after the last dose of study drug. 4. Males must be unable to procreate (defined as surgically sterile [i.e., had a vasectomy =6 months prior to Screening]) or must agree to use a highly effective form of birth control from Screening through 105 days (sum of 5-half-life and 90 days interval as per CTFG guidelines) after the last dose of study drug. 5. Clinical diagnosis of CMT2 or dHMN due to SORD Deficiency confirmed by medical record, elevated sorbitol level (>10,000 ng/mL), and gene analysis report confirming a pathogenic mutations in both the paternal and maternal SORD alleles (can be homozygous for the same mutation or compound heterozygous with two different pathogenic mutations). 6. Patient may be on concomitant medications and dietary supplements; however, they must be on stable doses for at least 1 month prior to Screening and throughout the study. In addition, all over-the-counter (OTC) and/or prescription medications must be reviewed and approved by the Investigator. 7. Willing and able to be confined to the clinical research unit (CRU) as required by the protocol. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Carrier of a single heterozygous mutation of the SORD gene 2. 10MWRT classified as very severe disease (e.g. 10MWRT >15 seconds to complete OR unable to complete 10MWRT without the use of an assistive device such as a cane/walker/wheelchair). 3. History or presence of clinically significant hematopoietic, renal, hepatic, endocrine (e.g. diabetes), metabolic, pulmonary, neurological (e.g. other neuropathy, myopathy or neuromuscular disorder), psychiatric, cardiovascular, immunological, dermatological, or gastrointestinal diseases that are -at priori- altering the proper evaluation of the safety and efficacy of AT-007; conditions capable of altering the absorption, metabolism, or elimination of drugs; or conditions that constitute a risk factor when taking the study drug and/or impact the conduct or results of the study. 4. Body Mass Index (BMI) >35 kg/m2. 5. BMI 1.5 x upper limit of normal (ULN) at Screening. 15. Urinary albumin-to-creatinine ratio (UACR) > 30 mg/g at Screening in the presence of elevated creatinine (>2X ULN). 16. History or presence of cardiovascular disorders including myocardial infarction, stroke, uncontrolled hypertension (sitting blood pressure =140/90 mmHg), left ventricular (LV) hypertrophy, atrial fibrillation, or valvular heart disease considered clinically significant by the Principal Investigator (PI). 17. Abnormal findings on the Screening 12-lead ECG, such as ST/T wave changes, pathological Q wave changes, or any rhythm other than normal sinus rhythm considered clinically significant by the PI. 18. Evidence of significant active hematological disease and/or cumulative blood donation of 1 unit (500 mL) or more including blood drawn during clinical studies in the last 3 months. 19. History of significant drug allergy or drug hypersensitivity. 20. Investigators, site personnel directly affiliated with this study, and their immediate families (defined as a spouse, parent, child, or sibling, whether biological or legally adopted). 21. Any other condition that, in the opinion of the Investigator, precludes the patient from following and completing the protocol. 22. A clinically significant abnormal finding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Clinical Outcome Objectives: • To evaluate the effect of long-term (24 months) administration of AT-007 on the 10 m walk/run test (10MWRT) in patients with SORD Deficiency 16 to 55 years of age Pharmacodynamic/Biomarker Objectives: • To evaluate the effect of long-term (12 months) administration of AT-007 on the levels of blood sorbitol in patients with SORD Deficiency • To evaluate the effect of long-term (12 months) administration of AT-007 on the levels of blood sorbitol in patients with SORD Deficiency;Secondary Objective: Clinical Outcome Objectives: • To evaluate the effect of long-term (24 months) administration of AT-007 on the Charcot Marie Tooth Health Index (CMTHI) score in patients with SORD Deficiency • To evaluate the safety of long-term administration and pharmacokinetic (PK) parameters of AT 007 in patients with SORD Deficiency Pharmacodynamic/Biomarker Objectives: • To evaluate the effect of long-term (12 months) administration of AT-007 on the CMT-related magnetic resonance imaging (MRI) parameters of disease progression inpatients with SORD Deficiency • To evaluate the effect of long-term (24 months) administration of AT-007 on the levels of blood sorbitol in patients with SORD Deficiency • To evaluate the effect of long-term administration (24 months only if Month 12 between-group difference [AT-007 minus placebo] is not statistically significant) of AT-007 on the CMT-related MRI parameters of disease progression in patients with SORD Deficiency ;Primary end point(s): Clinical Outcomes Analyses: 10MWRT Pharmacodynamic and Biomarker Analyses: Blood sorbitol ;Timepoint(s) of evaluation of this end point: Clinical Outcomes Analyses: 24 months Pharmacodynamic and Biomarker Analyses: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical Outcomes Analyses: CMTHI Pharmacodynamic and Biomarker Analyses: CMT related MRI parameters of disease progression Blood sorbitol ;Timepoint(s) of evaluation of this end point: Clinical Outcomes Analyses: 24 months Pharmacodynamic and Biomarker Analyses: 12 months 24 months | — |
Countries
Czechia, Czech Republic, Italy, United Kingdom, United States
Contacts
Public ContactManagement
Applied Therapeutics Inc.
Outcome results
None listed