Progerinin + Lonafarnib for Progeria
KD
Overseen ByKush Dhody, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: PRG Science & Technology Co., Ltd.
Must be taking: Lonafarnib
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Trial Summary
Do I need to stop my current medications for the trial?
The trial requires participants to continue taking lonafarnib, which is the standard treatment for Progeria. However, other drugs specifically targeting Progeria are not allowed, and medications that significantly affect the metabolism of Progerinin are also excluded. If you are taking such medications, you may need to stop them.
What data supports the effectiveness of the drug Progerinin + Lonafarnib for Progeria?
What is the purpose of this trial?
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.
Eligibility Criteria
This trial is for patients with Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic condition. Participants must be currently taking the standard treatment, Lonafarnib, and will either continue this alone or in combination with a new drug called Progerinin.Inclusion Criteria
I can travel to Boston for tests and exams.
I've been on lonafarnib for 4+ months without severe side effects for 2+ months.
I understand the study and its risks.
See 9 more
Exclusion Criteria
I am not taking any drugs specifically for Progeria, only for its symptoms.
I am on medication that affects Progerinin metabolism.
I have a stomach or intestine problem that affects how I absorb medicine.
See 5 more
Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive treatment with progerinin plus lonafarnib or lonafarnib alone. Dose escalation occurs through intra-subject dose titration.
4 months
Monthly visits for dose titration and monitoring
Toxicity Assessment
A 28-day period for toxicity assessment of the treatment.
4 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Progerinin
Trial Overview The study aims to find the best dose of Progerinin when used with Lonafarnib, and to check how safe and tolerable this combination is. Patients are randomly chosen to receive either just Lonafarnib or both drugs together.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Progerinin + LonafarnibExperimental Treatment2 Interventions
Subjects who have successfully completed the Screening phase will enter the treatment phase of the study and be randomized to a treatment arm. Subjects randomized to the progerinin + lonafarnib arm will take progerinin at a dose dependent on their body weight and will continue taking lonafarnib per the package insert.
For each dose cohort, subjects will complete a 28-day treatment period of toxicity assessment, and a minimum four-month treatment period for plasma progerin evaluation. After the last subject completes the toxicity assessment period, the independent Data Monitoring Committee (iDMC) will meet to confirm that subjects can be escalated to the next dose. All subjects will remain on the current dose until the iDMC decision is confirmed. Each subject will only be escalated to the next dose after their 4-month (±2 weeks) plasma progerin sample is collected.
Group II: Lonafarnib NaïveExperimental Treatment1 Intervention
Subjects with no prior treatment with lonafarnib (i.e., no commercial or managed access program source) may be enrolled to initiate treatment with lonafarnib monotherapy. These subjects will initiate lonafarnib therapy in preparation for an upcoming phase of the study following the completion of phase 2a. These subjects will be excluded from the analysis of this phase 2a study. They will come to the study site for a baseline visit and at one year for assessment as described later in this protocol.
Group III: LonafarnibActive Control1 Intervention
Subjects in the main study arms (Progerinin + Lonafarnib and non-naïve Lonafarnib) will continue taking lonafarnib per the package insert. Subjects randomized to the lonafarnib alone arm will not take progerinin during this study.
Find a Clinic Near You
Who Is Running the Clinical Trial?
PRG Science & Technology Co., Ltd.
Lead Sponsor
Trials
3
Recruited
90+
Findings from Research
In a study of 26 children with Hutchinson-Gilford progeria syndrome treated with lonafarnib for at least 2 years, there was a significant reduction in the frequency of clinical strokes, headaches, and seizures, suggesting improved neurologic status.
The treatment led to no new stroke events in patients with a history of transient ischemic attacks (TIAs), and four patients who had seizures before treatment did not experience any recurrent or new-onset seizures during the study.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment.Ullrich, NJ., Kieran, MW., Miller, DT., et al.[2021]
In a trial involving 37 participants with Hutchinson-Gilford progeria syndrome, a combination therapy of pravastatin, zoledronic acid, and lonafarnib resulted in a significant improvement in weight gain or carotid artery echodensity in 71% of participants, indicating its efficacy in managing some disease symptoms.
While the combination therapy improved bone mineral density, it did not provide additional cardiovascular benefits compared to lonafarnib alone, as evidenced by unchanged carotid artery wall echodensity and increased plaque formation.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.Gordon, LB., Kleinman, ME., Massaro, J., et al.[2018]
Progeria, a rare genetic disorder caused by mutations in the lamin A (LMNA) gene, provides valuable insights into the biology of premature aging and has led to the identification of potential drug targets through the farnesylation pathway.
Recent advancements include the development of animal models and the initiation of clinical trials aimed at treating children with progeria, marking significant progress in understanding and potentially addressing this condition.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
New approaches to progeria.Kieran, MW., Gordon, L., Kleinman, M.[2008]
References
Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. [2021]
Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. [2018]
New approaches to progeria. [2008]
Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. [2021]
Progeria: a rare genetic premature ageing disorder. [2021]
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