Ignite Creation Date:
2024-05-05 @ 10:05 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001596
Status:
COMPLETED
Last Update Posted:
2017-10-16
First Post:
1999-11-03
Brief Title:
Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
Sponsor:
William Gahl MD
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Therapeutic Clinical Trial of Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
Status:
COMPLETED
Status Verified Date:
2017-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hermansky-Pudlak Syndrome HPS is an inherited disease that results in decreased pigmentation oculocutaneous albinism bleeding problems due to a platelet abnormality platelet storage pool defect and storage of an abnormal fat-protein compound lysosomal accumulation of ceroid lipofuscin
The disease can cause poor functioning of the lungs intestine kidneys or heart The most serious complication of the disease is pulmonary fibrosis and typically causes death in patients 40 - 50 years old The disorder is common in Puerto Rico where many of the clinical research studies on the disease have been conducted Neither the full extent of the disease nor the basic cause of the disease is known There is no known treatment for HPS
The drug pirfenidone blocks the biochemical process of inflammation and has been reported to slow or reverse pulmonary fibrosis in animal systems
In this study researchers will select up to 40 HPS patients diagnosed with pulmonary fibrosis The patients will be randomly divided into 2 groups The patients will not know if they are taking pirfenidone or a placebo sugar pill
1 Group one will be patients who will receive pirfenidone
2 Group two will be patients who will receive a placebo sugar pill
The major outcome measurement of the therapy will be a change in the lung function forced vital capacity The study will be stopped if one therapy proves to be more effective than the other
The disease can cause poor functioning of the lungs intestine kidneys or heart The most serious complication of the disease is pulmonary fibrosis and typically causes death in patients 40 - 50 years old The disorder is common in Puerto Rico where many of the clinical research studies on the disease have been conducted Neither the full extent of the disease nor the basic cause of the disease is known There is no known treatment for HPS
The drug pirfenidone blocks the biochemical process of inflammation and has been reported to slow or reverse pulmonary fibrosis in animal systems
In this study researchers will select up to 40 HPS patients diagnosed with pulmonary fibrosis The patients will be randomly divided into 2 groups The patients will not know if they are taking pirfenidone or a placebo sugar pill
1 Group one will be patients who will receive pirfenidone
2 Group two will be patients who will receive a placebo sugar pill
The major outcome measurement of the therapy will be a change in the lung function forced vital capacity The study will be stopped if one therapy proves to be more effective than the other
Detailed Description:
Hermansky-Pudlak Syndrome HPS is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect The most serious complication of this disorder which is common in Puerto Rico is pulmonary fibrosis generally fatal in the fourth or fifth decade There is no treatment for the pulmonary disease of HPS which resembles idiopathic pulmonary fibrosis However a drug called pirfenidone has antifibrotic effects in animal models of lung fibrosis Pirfenidone is an IND drug initially provided by Marnac Inc InterMune Inc now holds the license Pirfenidone inhibits cytokine-induced inflammation Reported side effects include gastrointestinal upset a photosensitivity rash and palpitations Between 1997 and 2001 we performed a randomized placebo-controlled trial under this protocol that found pirfenidone to be safe and efficacious when analyzed using a repeated measures model Using a random coefficients model however the data were definitive only in the restricted group of subjects whose initial forced vital capacity was greater than 50 of predicted Because the repeated measures analysis had been chosen a priori as the optimal model the DSMB stopped the study and directed that all patients receive pirfenidone Of the 23 original patients 3 are still receiving pirfenidone under this protocol
Now to prove efficacy of pirfenidone we are conducting a block-randomized placebo-controlled double-blind trial involving up to 40 HPS patients whose forced vital capacity is 51-85 of predicted For every patient randomly assigned to the placebo group two will receive pirfenidone Patients are largely drawn from the Puerto Rican population and are simultaneously enrolled in clinical protocol 95-HG-193 They are admitted to the NIH Clinical Center for 2-3 day admissions every 4 months The primary efficacy variable is change in forced vital capacity determined on every admission Secondary efficacy variables are also examined A CT scan of the chest and bone densitometry are performed After 4 years of patient accrual 35 patients were enrolled the original statistical analysis plan SAP called for 39 patients to be enrolled within one year The NHGRI DSMB revised the original SAP to perform an interim data analysis 12 months after 30 patients were enrolled ie in May of 2009 That analysis directed the study to stop due to futility However this protocol will continue to provide pirfenidone to the three original protocol patients still enrolled and to any pirfenidone-treated patients who choose to undergo pulmonary lavage to help us determine the effects of pirfenidone on the cytokine profile of alveolar macrophages The lavages would require enrollment in a separate protocol The treatment drug will be stopped immediately for all placebo patients and for pirfenidone patients who do not plan to enroll in the lavage protocol Pirfenidone treatment will stop just after the lavage is performed on patients who do enroll in the lavage protocol 04-HG-0211 All patients will be invited to continue to come to the NIH annually under the HPS natural history protocol 95-HG-0193
Now to prove efficacy of pirfenidone we are conducting a block-randomized placebo-controlled double-blind trial involving up to 40 HPS patients whose forced vital capacity is 51-85 of predicted For every patient randomly assigned to the placebo group two will receive pirfenidone Patients are largely drawn from the Puerto Rican population and are simultaneously enrolled in clinical protocol 95-HG-193 They are admitted to the NIH Clinical Center for 2-3 day admissions every 4 months The primary efficacy variable is change in forced vital capacity determined on every admission Secondary efficacy variables are also examined A CT scan of the chest and bone densitometry are performed After 4 years of patient accrual 35 patients were enrolled the original statistical analysis plan SAP called for 39 patients to be enrolled within one year The NHGRI DSMB revised the original SAP to perform an interim data analysis 12 months after 30 patients were enrolled ie in May of 2009 That analysis directed the study to stop due to futility However this protocol will continue to provide pirfenidone to the three original protocol patients still enrolled and to any pirfenidone-treated patients who choose to undergo pulmonary lavage to help us determine the effects of pirfenidone on the cytokine profile of alveolar macrophages The lavages would require enrollment in a separate protocol The treatment drug will be stopped immediately for all placebo patients and for pirfenidone patients who do not plan to enroll in the lavage protocol Pirfenidone treatment will stop just after the lavage is performed on patients who do enroll in the lavage protocol 04-HG-0211 All patients will be invited to continue to come to the NIH annually under the HPS natural history protocol 95-HG-0193
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 97-HG-0085 | None | None | None |