Phase I Study of Progerinin in Healthy Volunteers
Condition: Hutchinson-Gilford Progeria Syndrome; Werner Syndrome
MeSH terms: Progeria; Werner Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      PRG Science & Technology Co., Ltd. (PRG S&T) is developing Progerinin (SLC-D011) for the
      treatment of the rare aging diseases Hutchinson-Gilford Progeria Syndrome (HGPS) and Werner
      Syndrome (WS).

      Progerin, an abnormal splice variant of the inner nuclear membrane protein lamin A is
      implicated in the pathology of HGPS and WS. It is believed that the extremely strong binding
      between lamin A and progerin is responsible for the nuclear abnormality phenotype observed in
      HGPS. WS is caused by functional defect of WRN, RecQ4L DNA helicase and rapid accumulation of
      progerin in WRN deficient condition is thought to be the cause of premature aging in WS. PRG
      S&T has shown that Progerinin binds specifically to progerin reduces its expression in both
      HGPS and WS cells, Progerinin further prevents progerin-lamin A in HGPS cells. In a progeria
      mouse model (LmnaG609G/G609G), treatment with Progerinin via intraperitoneal (i.p) injection
      (20 mg/kg, twice per week) could increase the body weight and extend the life span of
      LmnaG609G/G609G mice up to 21 weeks. In the LmnaG609G/+ mouse model, improved morphology such
      as status of coat hair and body size, increased body weight and extended life span for about
      16 weeks was noted following Progerinin treatment. In addition, Progerinin can suppress
      muscle weakness including the heart muscle. Safety pharmacology studies did not indicate any
      Progerinin-related effects on vital organs and systems including respiratory, cardiovascular
      and central nervous system.

      Prior to studies in the disease states, this study PRG-PRO-001, an initial first-in-human
      study, will be conducted in healthy volunteers to assess the safety, tolerability and
      pharmacokinetics of Progerinin. 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. The
      estimated enrollment is around 56 healthy volunteers, with 40 subjects estimated for the SAD
      phase and 16 subjects for the MAD Phase at one site in the USA.

      Expanded Access Program is available. For more details, please use the link in the References
      Section below to access our company's main webpage on Expanded Access Program.
    

Intervention name(s): Progerinin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 100 mg/g nano-suspension for oral use; A substance that has no therapeutic effect, used as a control in testing Progerinin
Other intervention name(s): SLC-D011; Vehicle control
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: HGPS; WS; Progeria