Safety Issues, Tolerance
Conditions
Brief summary
A Phase I, Randomized, Double-Blind, Placebo-Controlled, First-in-human, Single-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of retro enversio (RT) thymopentin in Healthy Adult Participants and Patients with Amyotrophic Lateral Sclerosis (ALS)
Detailed description
This is a first-in-human, randomized, double-blind, placebo-controlled, single-ascending-dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of retro enversio thymopentin (FC-12738) in healthy adult participants and patients with ALS. The clinical trial will be conducted in two parts, initially a SAD study in 3-sequential cohorts of healthy adult participants (PartA), and then follows another SAD study in 4-6-sequential cohorts of patients with ALS (Part B). Dose escalation in the SAD cohorts will be determined after having reviewed of the interim safety data as well as all available PK and/or PD data from the preceding dose level(s).
Interventions
DRUGFC-12738
Retro enversio pentapeptide of thymopentin
DRUGSaline
placebo
Sponsors
Neurodegenerative Disease Research Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Each dose cohort will enroll 8 healthy adults participants, participants will be randomly assigned to receive a single subcutaneous (SC) injection of FC-12738 or placebo in a ratio of 6:2, respectively.
Intervention model description
Each dose cohort will enroll 8 healthy adults participants, partipants will be randomly assigned to receive a single subcutaneous (SC) injection of FC-12738 or placebo in a ratio of 6:2, respectively.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must meet all of the following inclusion criteria at Screening to be eligible for participation in this study: 1. Part A healthy males or females between the ages of 18 and 65 years of age and Part B males and females aged between 18 and 80 years of age, inclusive at the times of signing the informed consent; 2. Female participants who: Are postmenopausal (over or equal to 1 year), OR Are surgically sterile, confirmed by medical documentations, OR If they are of child bearing potential, agree to use at least 1 highly effective method of contraception and 1 additional effective method at the same time, from at least 1 month prior to the initiation of the study through 3 months after the last administration. OR Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant; Agree to refrain from egg donation and in vitro fertilization during the entire study period and through 90 days after the last dose of study drug; Male participants, even if surgically sterilized (i.e., status postvasectomy), who: Agree to practice effective barrier contraception and avoid sperm donation during the entire study period and through 90 days after the last dose of study drug, OR Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant; 3. Able to give a signed written informed consent form (the informed consent form must be signed by the participant prior to any study-specific procedures); have a full understanding of the study content, procedures, and possible AEs; and be willing and able to comply with study procedures and follow-up examinations; 4. Results of vital signs, physical examination, laboratory examinations, abdominal and Chest X-ray, 12-lead electrocardiogram (ECG), and other examination at Screening or Baseline are normal or abnormal but not clinically significant. Assessment may be repeated once if deemed appropriate by the investigator; Part A: Additional Inclusion Criteria for Healthy Adult Participants: 5. Body mass index (BMI, weight \[kg\] / height2 \[m2\]) of 18 to 26 kg/m2, inclusively, with a minimum body weight of 50 kg for males, and 45 kg for females; Part B: Additional Inclusion Criteria for ALS Patients: 6. Diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS ≤ 24 months prior to screening, according to the World Federation of Neurology El Escorial criteria published in 2000 ; 7. Participants on riluzole or sodium phenylbutyrate/taurursodiol must be on a stable dose for at least 30 days prior to study enrollment; or patients on edaravone must have completed at least 2 cycles of dosing with edaravone at the time of screening or have not taken edaravone for at least 30 days prior to screening and not planning to start edaravone during the course of the study. Two cycles of dosing are defined as having completed Cycle 1 infusion, which is 14 consecutive days of intravenous (IV) edaravone followed by 14 days off edaravone, and Cycle 2, which is 10 out of 14 days of IV edaravone; 8. Slow vital capacity (SVC) ≥ 60% of predicted within 1 month prior to Treatment Day 1.
Exclusion criteria
Participants who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Injection site reactions in normal participants | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | Assessment of injection site reactions will be by observation (color) and palpation for soreness or thickening. |
| Physical exam by 12 lead electrocardiogram | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | 12-lead ECGs parameters will measure amplitude of the electrical wave in milimeters |
| Laboratory data will be measured by blood analysis | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | Levels of red blood cells will be measured by in number per microliter and white blood cells will be provided as a percent of total white count measured in number per microlliter. |
| Laboratory data will be measured by serum biochemistry and urinalysis | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | Serum biochemistry values and urine components will be measured in miligrams per deciliter |
| Characterize the safety/tolerability of single-ascending-dose study of FC-12738 in healthy adult participants | 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | AEs (Adverse Events), AEs of special interest (AESI), treatment-emergent AE (TEAE) and serious adverse events(SAE);Serious Adverse Event(s) AE's will be identified from the time of signed ICF (consent form), throughout the entire study until completion of the follow-up visit. |
| Measure blood pressure with a blood pressue cuff | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | blood pressure (BP) systolic and diastolic will be measured in millimeters of mercury (mmHg) |
| Heart rate measure | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | Heart rate will be measured by counting beats per minute |
| Physical exam signs by counting respiratory rate | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | respiratory rate (RR) will be measured in breaths per minute |
| Physical exam by temperature taken by a thermometer | at screening, Day-1, pre-dose and 0.5 hour, 1 hour, 2 hour, 4 hour, 8 hour, 24 hour, 48 hour, post-dose and follow-up visit on Day 8. | The temperature will be measured in degrees centegrade or Fahrenheit 12-lead ECGs parameters; Laboratory data (including fasting serum biochemistry, hematology, coagulation, and urinalysis); Assessment of injection site reactions; and Neurological examination； |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single-ascending-dose study of FC-12738 in healthy adult participants | 48 hours | Plasma PK parameters for each dose level will be calculated from the concentration of study drug measured in predose and postdose plasma samples. The PD parameters for each dose level will be calculated over time in predose and postdose plasma samples. The following parameters will be assessed during the trial: The area under the plasma concentration-time curve from time 0 extrapolated to infinity and from time 0 to the last measurable non-zero concentration. The area under the plasma concentration-time curve from time zero to 24 hours, the maximum observed concentration, the time to reach maximal value (Tmax). If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value. Apparent terminal elimination half-life of study drug, and apparent total plasma clearance. Urine PK parameters Cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts excreted over each time. |
| To determine the pharmacokinetic (PK) profiles in urine of single-ascending-dose study of FC-12738 in healthy adult participants | 48 hours | Urine PK parameters Cumulative urinary excretion from time zero to time t, calculated as the sum of the amounts of drug excreted over each time in micrograms per deciliter. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess the immunogenicity of single-ascending-dose study of FC-12738 in healthy adult participants | 24 hours post dosing and at 8 days | Changes from baseline in neuroinflammation relevant cytokines/chemokine levels, including but not limited to: TNF-α and IL-6; and changes from baseline in ALS-associated sphingomyelin, cerramides, and globosides. The proportion paticipants positive for anti-drug antibody (ADA) and neutralizing antibody (Nab) (if data permits) after a single drug dosing. |
Countries
United States
Outcome results
None listed