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Hutchinson-Gilford Progeria SyndromePhase 1NCT04512963

Phase I Study of Progerinin in Healthy Volunteers

A Phase 1 study testing Progerinin in people with Hutchinson-Gilford Progeria Syndrome and Werner Syndrome, run by PRG Science & Technology Co., Ltd. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
What is being tested?
Progerinin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
64 participants
Where
1 siteUnited States
Study dates
24 Aug 2020to 27 Jul 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • The subject has used prescription or over-the-counter (OTC) medication (other than ≤2 g/day paracetamol [acetaminophen] or ≤800 mg/day ibuprofen), vitamins, or herbal remedies, within 2 weeks or 5 half-lives before study drug administration, whichever is longer.
  • The subject has participated in another clinical study of a new investigational drug or has received an investigational drug within the 3 months or 5 half-lives (if available) before study drug administration, whichever is longer.
  • The subject has had a loss of more than 400 mL of blood (e.g. a blood donation) within 2 months before study drug administration, or has received any blood, plasma, or platelet transfusions within 3 months before check-in, or plans to donate blood during the study or within 3 months after the study.
  • The subject has a history of alcohol abuse (defined as an alcohol intake more than 21 units per week) or a history of drug abuse within the 6 months before study drug administration, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 240 mL of beer, 120 mL of wine, or 1 single shot of spirits. The subject will be required to abstain from alcohol consumption 48 hours prior to screening or check-in.
  • The subject is a current smoker or has a history of smoking.
  • The subject has a positive test for alcohol or drugs of abuse (barbiturates, methamphetamine, benzodiazepines, morphine/opiates, phencyclidine (PCP), amphetamines, tetrahydrocannabinol (THC), methylenedioxymethamphetamine (MDMA), cocaine, methadone, and cotinine) at screening or check-in.
  • The subject is unable to participate in, or successfully complete, the study, in the opinion of their general practitioner or the investigator, because the subject is any of the following:
  • mentally or legally incapacitated, or unable to give consent for any reason
  • in custody due to an administrative or a legal decision, or under tutelage, or being admitted to a sanitarium or social institution
  • unable to be contacted in case of emergency
  • unlikely to cooperate or comply with the clinical study protocol or is unsuitable for any other reason

Trial locations and contacts

1 site in 1 country.

United States1 site

  • PRG S&T Investigational Site

    Glendale, California, 91206

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
Progerinin, Placebo
Keywords
HGPS, WS, Progeria
Medical subject headings
Progeria, Werner Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ProgerininDrug

    Also called SLC-D011

    100 mg/g nano-suspension for oral use

  • PlaceboDrug

    Also called Vehicle control

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

Study groups in NCT04512963
Study groupRoleWhat they receive
SAD Phase including Food InteractionExperimentalSingle Ascending Dose (SAD) study with up to 6 cohorts + Food interaction phase on two cohorts
Receives: Drug: Progerinin; Drug: Placebo
MAD PhaseExperimentalMultiple Ascending Dose (MAD) study with up to 2 cohorts
Receives: Drug: Progerinin; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 through 7 days after the last study drug administration

  2. 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.

    Measured: Day 1 through 7 days after the last study drug administration

  3. Incidence of withdrawals due to Adverse Events (AEs)

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

    Measured: Day 1 through 7 days after the last study drug administration

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

    Measured: 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

  5. Change in vital signs

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

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

  6. Incidence of abnormal ECG parameters

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

  7. Incidence of abnormal physical examination findings

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

  8. Maximum observed plasma drug concentration (Cmax)

    Measured: 0-96 hours

  9. Apparent terminal elimination half-life (t1/2)

    Measured: 0-96 hours

  10. Time to maximum observed plasma drug concentration (Tmax)

    Measured: 0-96 hours

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

    Measured: 0-96 hours

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

    Measured: 0-96 hours

  13. Apparent plasma clearance (CL/F)

    Measured: 0-96 hours

  14. Apparent Volume of distribution (Vz/F)

    Measured: 0-96 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2020
  2. Study start24 Aug 2020
  3. Primary completion27 Jul 2021
  4. Study completion27 Jul 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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 blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04512963
Sponsor's protocol ID
PRG-PRO-001
Status last verified
Sep 2021
First submitted
6 Aug 2020
Last updated
22 Sep 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Progerinin in people with Hutchinson-Gilford Progeria Syndrome and Werner Syndrome, run by PRG Science & Technology Co., Ltd. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose Limiting Toxicities (DLTs) (time frame: Day 1 through 7 days after the last study drug administration). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04512963.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2021.

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