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: Powder for oral suspension
INN or Proposed INN: Govorestat
CAS Number: 2170729-29-8
Current Sponsor code: AT-007
Other descriptive
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. 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 an acceptable form of birth control from Screening until 30 days 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 an acceptable form of birth control from Screening through 30 days after the last dose of study drug. 5. Clinical diagnosis of CMT2 or dHMN due to SORD Deficiency confirmed by medical record or written communication by health care professional, elevated sorbitol level (>10,000 ng/mL), and gene analysis report indicating a biallelic mutation in SORD. 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: 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. 10MWRT classified as severe disease, as described in the operating manual. 2. 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. 3. Body Mass Index (BMI) >35 kg/m2. 4. Clinically relevant underweight, weight loss suggestive of a pathology unrelated to SORD deficiency, or 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) and/or Sponsor medical representative. 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 and/or Sponsor medical representative. (For the others Exl. criteria please refer to the Protocol)
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 percentage of fat in lower extremity muscle as assessed by magnetic resonance imaging (MRI) in patients 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 percentage of fat in lower extremity muscle as assessed by MRI 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: Percentage of fat in lower extremity muscle as assessed by MRI 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