ACTIVE_NOT_RECRUITING

Study to Determine Optimal Dose and Evaluate Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Researchers will compare treatment with progerinin plus lonafarnib vs lonafarnib alone to assess optimal dosing, safety, tolerability, and pharmacokinetics in patients with Hutchinson-Gilford Progeria Syndrome (HGPS). Subjects in the randomized study arms will continue to take the standard of care (SOC), lonafarnib, and will be randomized to either take SOC alone or in combination with progerinin.

Official Title

A Phase 2a, Randomized, Open-Label Study to Determine the Optimal Dose and Evaluate the Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)

Quick Facts

Study Start:2025-01-13

Study Completion:2026-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06775041

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subjects ≥ 1 year of age and weight ≥ 17.6 lb (8 kg). 2. Subject must have confirmatory mutational analysis showing the classic HGPS mutation (c. 1824 C\>T), nonclassic HGPS, Zmpset24 gene mutation, or other LMNA mutation (all subjects will havedocumentation of genetic testing prior to enrollment). \*Only subjects with progerin producing mutations will be eligible for randomization. Other PL are eligible to enroll as naïve subjects (see note for criterion #5). 3. Subject must display clinical signs of Progeria as per the clinical trial team. 4. Subject must be willing and able to come to Boston for appropriate assessments and examinations. 5. Subject must be taking lonafarnib for at least 4 months prior to enrollment and have no history of grade 3 or 4 side effects that can be probably or possibly attributed to lonafarnib for at least 2 months prior to enrollment. 6. Subjects must have had no recent fractures or major surgery (within four weeks). 7. Subject must have adequate organ and marrow function as defined by the following parameters: 1. Blood: APC (ANC + bands + monocytes) \>1,000/µL, platelets \>75,000/µL (transfusion independent); hemoglobin \>9 g/dL. 2. Renal: creatinine ≤ 1.5 times normal for age or Glomerular Filtration Rate (GFR) \>70 mL/min/1.73m2. 3. Hepatic: bilirubin ≤1.5x upper limit of normal for age; Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Transaminase, \[ALT\]) \< and Serum Glutamic-Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, \[AST\]) ≤ 2.5x normal range for age. 8. The subject is willing to provide written informed assent form, when possible, to participate in the study after reading the informed assent form and the information provided and has had the opportunity to discuss the study with the investigator or designee. Additionally, the subject's legally authorized guardian (LAR) is willing to provide written informed consent. 9. The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study. 10. The subject (or LAR) is able to understand the nature of the study and any potential hazards associated with participating in it. 11. Negative pregnancy test for female subjects of childbearing potential and those who have not been surgically sterilized or who do not have verbal or laboratory confirmation of two years postmenopausal status. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Women of childbearing potential should use an acceptable method of birth control and agree to continue to use this method for the duration of the study and for 90 days after taking the last dose of Progerinin.	1. Other than the drugs used in this protocol, other drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted. 2. Subjects are taking medications that significantly affect the metabolism of Progerinin. 3. Subjects with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin). 4. Subjects who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: 1. known severely impaired lung function 2. active (acute or chronic) or uncontrolled severe infections. 3. liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. 4. history of hepatitis B or hepatitis C documented by history and confirmed by serology if positive for history. 5. Other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration). 6. A known history of Human Immunodeficiency Virus (HIV) seropositivity or known immunodeficiency. 7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Progerinin (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed. 8. Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated. 9. Subjects who have used marijuana or other (Tetrahydrocannabinol) THC containing products either recreationally or for medical purposes within three months prior to entering the study.

Inclusion Criteria

Exclusion Criteria

1. Subjects ≥ 1 year of age and weight ≥ 17.6 lb (8 kg).
2. Subject must have confirmatory mutational analysis showing the classic HGPS mutation (c. 1824 C\>T), nonclassic HGPS, Zmpset24 gene mutation, or other LMNA mutation (all subjects will havedocumentation of genetic testing prior to enrollment). \*Only subjects with progerin producing mutations will be eligible for randomization. Other PL are eligible to enroll as naïve subjects (see note for criterion #5).
3. Subject must display clinical signs of Progeria as per the clinical trial team.
4. Subject must be willing and able to come to Boston for appropriate assessments and examinations.
5. Subject must be taking lonafarnib for at least 4 months prior to enrollment and have no history of grade 3 or 4 side effects that can be probably or possibly attributed to lonafarnib for at least 2 months prior to enrollment.
6. Subjects must have had no recent fractures or major surgery (within four weeks).
7. Subject must have adequate organ and marrow function as defined by the following parameters:
1. Blood: APC (ANC + bands + monocytes) \>1,000/µL, platelets \>75,000/µL (transfusion independent); hemoglobin \>9 g/dL.
2. Renal: creatinine ≤ 1.5 times normal for age or Glomerular Filtration Rate (GFR) \>70 mL/min/1.73m2.
3. Hepatic: bilirubin ≤1.5x upper limit of normal for age; Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Transaminase, \[ALT\]) \< and Serum Glutamic-Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, \[AST\]) ≤ 2.5x normal range for age.
8. The subject is willing to provide written informed assent form, when possible, to participate in the study after reading the informed assent form and the information provided and has had the opportunity to discuss the study with the investigator or designee. Additionally, the subject's legally authorized guardian (LAR) is willing to provide written informed consent.
9. The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
10. The subject (or LAR) is able to understand the nature of the study and any potential hazards associated with participating in it.
11. Negative pregnancy test for female subjects of childbearing potential and those who have not been surgically sterilized or who do not have verbal or laboratory confirmation of two years postmenopausal status. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Women of childbearing potential should use an acceptable method of birth control and agree to continue to use this method for the duration of the study and for 90 days after taking the last dose of Progerinin.

1. Other than the drugs used in this protocol, other drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted.
2. Subjects are taking medications that significantly affect the metabolism of Progerinin.
3. Subjects with an active bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin).
4. Subjects who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
1. known severely impaired lung function
2. active (acute or chronic) or uncontrolled severe infections.
3. liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
4. history of hepatitis B or hepatitis C documented by history and confirmed by serology if positive for history.
5. Other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
6. A known history of Human Immunodeficiency Virus (HIV) seropositivity or known immunodeficiency.
7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Progerinin (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed.
8. Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
9. Subjects who have used marijuana or other (Tetrahydrocannabinol) THC containing products either recreationally or for medical purposes within three months prior to entering the study.

Contacts and Locations

Study Locations (Sites)

Boston Children's Hospital

Boston, Massachusetts, 02115

United States

Collaborators and Investigators

Sponsor: PRG Science & Technology Co., Ltd.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-13

Study Completion Date2026-03

Study Record Updates

Study Start Date2025-01-13

Study Completion Date2026-03

Terms related to this study

Additional Relevant MeSH Terms

Hutchinson-Gilford Progeria Syndrome