Phase I Study of Progerinin in Healthy Volunteers

NCT04512963 | Completed Phase 1 FDA Drug

• 1 other identifier: PRG-PRO-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

PRG-PRO-001 is a Phase I, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose (SAD) Study including a food interaction study, followed by a Multiple Ascending Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Profile of Progerinin in Healthy Volunteers. This is a first-in-human study. The study aims to determine the safety and tolerability of Progerinin after single and multiple doses in healthy volunteers and to evaluate the pharmacokinetics (PK) of Progerinin after single and multiple dose administrations in healthy volunteers.

Conditions

Hutchinson-Gilford Progeria Syndrome; Werner Syndrome

Keywords

HGPS; WS; Progeria

Outcome Measures

Primary Outcomes (14)

• Incidence of Dose Limiting Toxicities (DLTs)

  Any clinically significant adverse event (AE)/serious adverse event (SAE) or clinically significant laboratory abnormality which is classified as \> Grade 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0), where applicable, deemed by the investigator as at least "possibly, probably or definitely related" to Progerinin but unrelated to concurrent illness, or concomitant medications.

  Day 1 through 7 days after the last study drug administration

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease that occurs or is reported by the patient to have occurred, or a worsening of a pre-existing condition. An adverse event may or may not be related to the study treatment.

  Day 1 through 7 days after the last study drug administration

• Incidence of withdrawals due to Adverse Events (AEs)

  Incidence of withdrawals due to Adverse Events (AEs) defined above

  Day 1 through 7 days after the last study drug administration

• Incidence of abnormal blood work tests results, abnormal Urinalysis and positive Pregnancy test

  At baseline, 72 to 96 hours after the last study drug administration, and on Day 7 after the first and the last study drug administration

• Change in vital signs

  Vital signs measurement includes blood pressure (both systolic and diastolic blood pressures), pulse, temperature and respiratory rate.

  At pre-dose, over 96 hours after study drug administration, and on Day 7 after the last study drug administration

• Incidence of abnormal ECG parameters

  At pre-dose, over 96 hours after study drug administration, and on Day 7 after the last study drug administration

• Incidence of abnormal physical examination findings

  At baseline, 96 hours after the last study drug administration, and on Day 7 after the last study drug administration

• Maximum observed plasma drug concentration (Cmax)

  0-96 hours

• Apparent terminal elimination half-life (t1/2)

  0-96 hours

• Time to maximum observed plasma drug concentration (Tmax)

  0-96 hours

• Area under the plasma drug concentration-time curve (AUC)

  0-96 hours

• Percentage of AUC0-∞ extrapolated from Tlast to infinity (AUCext)

  0-96 hours

• Apparent plasma clearance (CL/F)

  0-96 hours

• Apparent Volume of distribution (Vz/F)

  0-96 hours

Study Arms (2)

SAD Phase including Food Interaction

EXPERIMENTAL

Single Ascending Dose (SAD) study with up to 6 cohorts + Food interaction phase on two cohorts

Drug: Progerinin; Drug: Placebo

MAD Phase

EXPERIMENTAL

Multiple Ascending Dose (MAD) study with up to 2 cohorts

Drug: Progerinin; Drug: Placebo

Interventions

Progerinin DRUG

100 mg/g nano-suspension for oral use

Also known as: SLC-D011

MAD Phase; SAD Phase including Food Interaction

Placebo DRUG

A substance that has no therapeutic effect, used as a control in testing Progerinin

Also known as: Vehicle control

MAD Phase; SAD Phase including Food Interaction

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria:
• Healthy male and female subjects, 18 to 45 years of age, inclusive.
• The subject has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, and weighs at least 50 kg.
• The subject is in good health and has no medical condition of clinical significance or that may impact the outcome of the study, as determined by the investigator (as determined by medical history, physical examination, 12-lead electrocardiogram \[ECG\], vital signs, and clinical laboratory results at screening).
• The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
• The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
• The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided, and has had the opportunity to discuss the study with the investigator or designee.
• Negative pregnancy test for female subjects. Women of child bearing potential (WOCBP) and Women not of child bearing potential are eligible to participate. Both women of child bearing potential and women of no child bearing potential should use an approved method of birth control and agrees to continue to use this method for the duration of the study (and for 90 days after taking the last dose of Progerinin).
• Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile or 2 years post-menopausal. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study and for 90 days after taking the study drug. In addition, subjects may not donate sperm for the duration of the study and for 90 days after taking study drug.
• Subjects not taking any medications or dietary supplements (i.e., St. John's Wort and goldenseal) which are inhibitors or inducers of CYP 3A4 and CYP 2D6 during screening and for the duration of the trial.
• Subjects not taking any medications which are substrates of CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5 during screening and for the duration of the trial.

You may not qualify if:

• Subjects will be eligible for enrollment in the study only if they meet NONE of the following criteria:
• The subject has a history of severe allergic or anaphylactic reactions.
• The subject has a known allergy or hypersensitivity to any component of the formulation.
• The subject has a medical history or current evidence of any clinically significant (as determined by the investigator) cardiac, endocrine (including diabetes), hematologic, hepatobiliary (abnormal 12lanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyl transpeptidase \[GGT\], or total bilirubin), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal condition, or other major disease.
• The subject has a history of any malignant disease.
• The subject has a history of more than one herpes zoster episode or multimetameric herpes zoster.
• The subject has a history of an opportunistic infection (e.g. cytomegalovirus, pneumocystis carinii, aspergillosis, clostridium difficile).
• The subject has a history of or ongoing chronic or recurrent infectious disease (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis).
• The subject has had major trauma or surgery in the 2 months before screening or at any time between screening and check-in.
• The subject has had an acute infection within 2 weeks before screening or at any time between screening and check-in including, but not limited to, history, signs, or symptoms of a common cold (eg, mild rhinorrhea), untreated oral/dental abnormalities (e.g. untreated dental caries as determined by examination of the mouth), or untreated disruption of the skin.
• The subject has clinically significant abnormal ECG findings at screening, check-in visits, or predose, as determined by the Investigator.
• The subject has a supine blood pressure measurement outside the ranges of 90 to 140 mm Hg systolic or 45 to 90 mm Hg diastolic (measured after a rest of at least 5 minutes) at screening, check-in, or predose. Note: If either value is out of the range, blood pressure measurements may be repeated in the supine position at intervals of 5 to 10 minutes up to 3 times. If the mean systolic or diastolic measurement continues to exceed the stated limits, the subject will be excluded.
• The subject has a pulse of fewer than 45 beats per minute (bpm) or greater than 100 bpm (measured after a rest of at least 5 minutes) at screening, check-in, or predose.
• The subject tests positive for tuberculosis (TB) at screening by the QuantiFERON-TB Gold Test, or has a history of latent, inadequately treated, or active TB.
• The subject has a known history of, or a positive test result for, hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) types 1 or 2 at screening.

Sponsors & Collaborators

• PRG Science & Technology Co., Ltd.: lead
• Amarex Clinical Research: collaborator

Study Sites (1)

PRG S&T Investigational Site

Glendale, California, 91206, United States

Location

Related Links

• PRG S\&T Expanded Access Program

MeSH Terms

Conditions

Progeria; Werner Syndrome

Condition Hierarchy (Ancestors)

Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; DNA Repair-Deficiency Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SAD Phase including Food Interaction: This is a randomized, double-blind, placebo-controlled, dose-escalating study in healthy volunteers. Participants will be assigned to 1 of up to 6 cohorts and will be randomized within each cohort to Progerinin or placebo at 3:1 ratio. Following the completion of the SAD phase, if study stopping criteria (SSC) is not met, then participants in cohort 5 and 6 will cross-over to the fed part of the study following a 7 day washout period. If SSC is achieved in the SAD phase, then the previous dose will be in the Food Interaction phase. MAD Phase: This is a randomized, double-blind, placebo-controlled, dose-escalating study in healthy volunteers. If SSC is not met in the SAD phase, then participants will be assigned to 1 of 2 cohorts and will be randomized within each cohort to Progerinin or placebo at 3:1 ratio. If SSC is achieved in the SAD phase, then the previous two doses will be used as the 2 cohorts in the MAD phase.

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 14, 2020
• Study Start: August 24, 2020
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)