ProgeriaPhase 2NCT00916747
Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
A Phase 2 study testing Lonafarnib, Zoledronic Acid, and Pravastatin in people with Progeria, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Hutchinson-Gilford Progeria Syndrome (Progeria) is a rare autosomal disease that results in premature death at a median age of 13 years due to cardiovascular and cerebralvascular compromise. The mutation for this disease has been identified and results in a mutant form of lamin A that cannot be de-farnesylated. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Progeria
- What is being tested?
- Lonafarnib, Zoledronic Acid, and Pravastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Dec 2023
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Genetic Diagnosis: All patients must have confirmatory mutational analysis showing mutation in the lamin A gene.
- Clinical Diagnosis: Patients must display clinical signs of progeria as per the clinical trial team.
- Travel: Patients must be willing and able to come to Boston for appropriate studies and examinations at initiation of study and at months 6, 12, 18 and 24 on study.
- Patient must have adequate organ and marrow function as defined by the following parameters:
- Blood: APC (ANC + bands + monocytes = APC) > 1,000/microliters, Platelets > 75,000/microliters (transfusion independent); Hemoglobin >9g/dl.
- Renal: creatinine Less than or equal 1.5 times normal for age or GFR > 70 ml/min/1.73m2.
Show all 11Show fewer
- Hepatic: bilirubin Less than or equal to 1.5 x upper limit of normal for age; SGPT (ALT) < and SGOT (AST) < 5 x normal range for age.
- PT/PTT: PT/PTT < 120% upper limit of normal OR PI approval
- No overt renal, hepatic, pulmonary disease or immune dysfunction.
- 25-hydroxyvitamin D ≥ 20 ng/ml within 4 weeks of bisphosphonate infusion.
- Signed informed consent according to institutional guidelines must be obtained and patient must begin therapy within twenty eight (28) days.
Who cannot join
- Other than the drugs used in this protocol, drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted.
- Patients must not be taking medications that significantly affect the metabolism of lonafarnib at the time they start lonafarnib
- Patient must have no uncontrolled infection.
- Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
- Patients must not be pregnant or breast-feeding. Female patients of childbearing potential must have negative serum or urine pregnancy test. Male and female patients of reproductive potential must agree to use a medically accepted form of birth control while on study and up to 10 weeks after treatment. It is permissible for female patients to take oral contraceptives or other hormonal methods while receiving treatment with lonafarnib.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
Official title: An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies
Hutchinson-Gilford Progeria Syndrome (Progeria) is a rare autosomal disease that results in premature death at a median age of 13 years due to cardiovascular and cerebralvascular compromise. The mutation for this disease has been identified and results in a mutant form of lamin A that cannot be de-farnesylated. This study evaluates the combination of pravastain (a statin), lonafarnib (a farnesyltransferase inhibitor) and zoledronic acid (a bisphosphonate) in an open label phase II efficacy trial in children with Progeria. These agents all target farnesylation pathways at different points. Patients with genetically confirmed progeria will be eligible for this protocol. Treatment will be initiated for 24 months duration. Clinical and biologic parameters will be examined to assess response.
- Conditions
- Progeria
- Being tested
- Lonafarnib, Zoledronic Acid, and Pravastatin
- Keywords
- Progeria
- Medical subject headings
- Progeria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lonafarnib, Zoledronic Acid, and PravastatinDrug
Lonafarnib: Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Lonafarnib will be orally administered without planned breaks, approximately every 12 hours, for a period of 24 months. For patients unable to swallow capsules, the capsules can be opened and dissolved into Ora Blend SF or Ora-Plus.
Zoledronic Acid: Zoledronic acid will be administered intravenously at week one, and months 6, 12, 18 and 24 of this treatment trial. Treatment will consist of one infusion over a 30 minute period.
Pravastatin: Pravastatin will be orally administered once daily without planned breaks, approximately every 24 hours, for a period of 24 months. The drug may be taken with meals. For patients unable to swallow pills, pills can be crushed into food. Pravastatin will be dosed according to the patient weight. Patients less than 10 kg will receive 5 mg pravastatin orally, once daily. Patients weighing 10 kg or greater will receive 10 mg pravastatin daily.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | All patients will receive zoledronic acid, pravastatin and lonafarnib Receives: Drug: Lonafarnib, Zoledronic Acid, and Pravastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS.
Measured: 2 years
Secondary outcomes (8)
To describe any acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib.
Measured: 2 years
To investigate which clinical and laboratory studies are needed to monitor or alter therapy to prevent unacceptable toxicity.
Measured: 2 years
To assess the pharmacokinetics of lonafarnib in patients with progeria.
Measured: 2 years
To assay for the inhibition of HDJ-2 farnesylation in Peripheral Blood Leukocytes (PBL).
Measured: 2 years
To assay for changes in research-based potential markers of efficacy such as levels of prelamin A, mature lamin A, progerin, and HP1 in protein isolated from PBL.
Measured: 2 years
To assess changes in leptin levels, glucose utilization, skeletal abnormalities including bone mineral density and X-ray finding, joint contracture and function, and growth
Measured: 2 years
To assess changes in auditory function, dental anomalies, dermatologic changes including hair density, nutrition with calorie analysis and energy expenditure, body composition analysis by DXA scan, and cardiovascular structure and function.
Measured: 2 years
To compare and incorporate clinical and laboratory data obtain from this study with that obtained during the single agent lonafarnib trial as well as the pilot combination trial of zoledronic acid, pravastatin and lonafarnib
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2009 (estimated)
- Study startAug 2009
- Primary completionFeb 2022
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ProgeriaStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough, Merck Sharp & Dohme LLC, Eiger BioPharmaceuticals
- Responsible party
- Principal investigator, Monica E. Kleinman, Boston Children's Hospital
- Investigators
- Mark Kieran, MD, PhD, Principal investigator, Children's Hospital Boston/ Dana-Farber Cancer Instittue
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00916747
- Sponsor's protocol ID
- Progeria Efficacy
- Status last verified
- Feb 2023
- First submitted
- 5 Jun 2009
- Last updated
- 27 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gordon LB, Norris W, Hamren S, Goodson R, LeClair J, Massaro J, Lyass A, D'Agostino RB Sr, Tuminelli K, Kieran MW, Kleinman ME. Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation. Circulation. 2023 Jun 6;147(23):1734-1744. doi: 10.1161/CIRCULATIONAHA.122.060002. Epub 2023 Mar 15.
PubMed 36919608Suzuki M, Jeng LJB, Chefo S, Wang Y, Price D, Li X, Wang J, Li RJ, Ma L, Yang Y, Zhang X, Zheng N, Zhang K, Joseph DB, Shroff H, Doan J, Pacanowski M, Smpokou P, Donohue K, Joffe HV. FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies. Genet Med. 2023 Feb;25(2):100335. doi: 10.1016/j.gim.2022.11.003. Epub 2022 Dec 12.
PubMed 36507973Gordon LB, Kleinman ME, Massaro J, D'Agostino RB Sr, Shappell H, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland RH, Nazarian A, Snyder BD, Ullrich NJ, Silvera VM, Liang MG, Quinn N, Miller DT, Huh SY, Dowton AA, Littlefield K, Greer MM, Kieran MW. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016 Jul 12;134(2):114-25. doi: 10.1161/CIRCULATIONAHA.116.022188.
PubMed 27400896Gordon LB, Massaro J, D'Agostino RB Sr, Campbell SE, Brazier J, Brown WT, Kleinman ME, Kieran MW; Progeria Clinical Trials Collaborative. Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014 Jul 1;130(1):27-34. doi: 10.1161/CIRCULATIONAHA.113.008285. Epub 2014 May 2.
PubMed 24795390
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies
- ClinicalTrials.gov ID
- NCT00916747
- Acronym / sponsor ID
- Progeria Efficacy
- Conditions
- Progeria
- Keywords
- Progeria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Schering-Plough, Merck Sharp & Dohme LLC, Eiger BioPharmaceuticals
- Study start
- Aug 2009
- Primary completion
- Feb 2022 (actual)
- Study completion
- Dec 2023 (estimated)
- First posted
- 9 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hutchinson-Gilford Progeria Syndrome (Progeria) is a rare autosomal disease that results in premature death at a median age of 13 years due to cardiovascular and cerebralvascular compromise. The mutation for this disease has been identified and results in a mutant form of lamin A that cannot be de-farnesylated. This study evaluates the combination of pravastain (a statin), lonafarnib (a farnesyltransferase inhibitor) and zoledronic acid (a bisphosphonate) in an open label phase II efficacy trial in children with Progeria. These agents all target farnesylation pathways at different points. Patients with genetically confirmed progeria will be eligible for this protocol. Treatment will be initiated for 24 months duration. Clinical and biologic parameters will be examined to assess response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Lonafarnib, Zoledronic Acid, and PravastatinAll patients will receive zoledronic acid, pravastatin and lonafarnib |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Genetic Diagnosis: All patients must have confirmatory mutational analysis showing mutation in the lamin A gene.
- Clinical Diagnosis: Patients must display clinical signs of progeria as per the clinical trial team.
- Travel: Patients must be willing and able to come to Boston for appropriate studies and examinations at initiation of study and at months 6, 12, 18 and 24 on study.
- Patient must have adequate organ and marrow function as defined by the following parameters:
- Blood: APC (ANC + bands + monocytes = APC) > 1,000/microliters, Platelets > 75,000/microliters (transfusion independent); Hemoglobin >9g/dl.
Key exclusion criteria (5 listed)
- Other than the drugs used in this protocol, drugs targeted to treat Progeria are excluded. Drugs to treat symptoms of Progeria are permitted.
- Patients must not be taking medications that significantly affect the metabolism of lonafarnib at the time they start lonafarnib
- Patient must have no uncontrolled infection.
- Subjects who have known or suspected hypersensitivity to any of the excipients included in the formulation should not be treated.
- Patients must not be pregnant or breast-feeding. Female patients of childbearing potential must have negative serum or urine pregnancy test. Male and female patients of reproductive potential must agree to use a medically accepted form of birth control while on study and up to 10 weeks after treatment. It is permissible for female patients to take oral contraceptives or other hormonal methods while receiving treatment with lonafarnib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lonafarnib, Zoledronic Acid, and PravastatinLonafarnib: Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Lonafarnib will be orally administered without planned breaks, approximately every 12 hours, for a period of 24 months. For patients unable to swallow capsules, the capsules can be opened and dissolved into Ora Blend SF or Ora-Plus. Zoledronic Acid: Zoledronic acid will be administered intravenously at week one, and months 6, 12, 18 and 24 of this treatment trial. Treatment will consist of one infusion over a 30 minute period. Pravastatin: Pravastatin will be orally administered once daily without planned breaks, approximately every 24 hours, for a period of 24 months. The drug may be taken with meals. For patients unable to swallow pills, pills can be crushed into food. Pravastatin will be dosed according to the patient weight. Patients less than 10 kg will receive 5 mg pravastatin orally, once daily. Patients weighing 10 kg or greater will receive 10 mg pravastatin daily. | Drug | Treatment arm |
Primary outcome
To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS.
Time frame: 2 years
8 secondary outcomes
To describe any acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib.
Time frame: 2 years
To investigate which clinical and laboratory studies are needed to monitor or alter therapy to prevent unacceptable toxicity.
Time frame: 2 years
To assess the pharmacokinetics of lonafarnib in patients with progeria.
Time frame: 2 years
To assay for the inhibition of HDJ-2 farnesylation in Peripheral Blood Leukocytes (PBL).
Time frame: 2 years
To assay for changes in research-based potential markers of efficacy such as levels of prelamin A, mature lamin A, progerin, and HP1 in protein isolated from PBL.
Time frame: 2 years
To assess changes in leptin levels, glucose utilization, skeletal abnormalities including bone mineral density and X-ray finding, joint contracture and function, and growth
Time frame: 2 years
To assess changes in auditory function, dental anomalies, dermatologic changes including hair density, nutrition with calorie analysis and energy expenditure, body composition analysis by DXA scan, and cardiovascular structure and function.
Time frame: 2 years
To compare and incorporate clinical and laboratory data obtain from this study with that obtained during the single agent lonafarnib trial as well as the pilot combination trial of zoledronic acid, pravastatin and lonafarnib
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Derived from this study: PubMed 36919608Gordon LB, Norris W, Hamren S, Goodson R, LeClair J, Massaro J, Lyass A, D'Agostino RB Sr, Tuminelli K, Kieran MW, Kleinman ME. Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation. Circulation. 2023 Jun 6;147(23):1734-1744. doi: 10.1161/CIRCULATIONAHA.122.060002. Epub 2023 Mar 15.
- Derived from this study: PubMed 36507973Suzuki M, Jeng LJB, Chefo S, Wang Y, Price D, Li X, Wang J, Li RJ, Ma L, Yang Y, Zhang X, Zheng N, Zhang K, Joseph DB, Shroff H, Doan J, Pacanowski M, Smpokou P, Donohue K, Joffe HV. FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies. Genet Med. 2023 Feb;25(2):100335. doi: 10.1016/j.gim.2022.11.003. Epub 2022 Dec 12.
- Derived from this study: PubMed 27400896Gordon LB, Kleinman ME, Massaro J, D'Agostino RB Sr, Shappell H, Gerhard-Herman M, Smoot LB, Gordon CM, Cleveland RH, Nazarian A, Snyder BD, Ullrich NJ, Silvera VM, Liang MG, Quinn N, Miller DT, Huh SY, Dowton AA, Littlefield K, Greer MM, Kieran MW. Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome. Circulation. 2016 Jul 12;134(2):114-25. doi: 10.1161/CIRCULATIONAHA.116.022188.
- Derived from this study: PubMed 24795390Gordon LB, Massaro J, D'Agostino RB Sr, Campbell SE, Brazier J, Brown WT, Kleinman ME, Kieran MW; Progeria Clinical Trials Collaborative. Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome. Circulation. 2014 Jul 1;130(1):27-34. doi: 10.1161/CIRCULATIONAHA.113.008285. Epub 2014 May 2.
- The Progeria Research FoundationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Kieran, MD, PhD principal investigator
Children's Hospital Boston/ Dana-Farber Cancer Instittue
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lonafarnib, Zoledronic Acid, and Pravastatin in people with Progeria, run by Boston Children's Hospital 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 5 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: status not confirmed, as of the sponsor's last update on 27 Feb 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
To evaluate the therapeutic effects of the combination of zoledronic acid, pravastatin and lonafarnib in patients with HGPS. (time frame: 2 years). 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 NCT00916747, which also lists 4 linked publications.
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 27 Feb 2023.