A Phase 2 interventional study of Pirfenidone and Placebo in Albinism, Inborn Errors of Metabolism and Oculocutaneous Albinism, sponsored by William Gahl, M.D.. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-10-16.
Sponsored by William Gahl, M.D. · Phase 2, Interventional, and Treatment
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".
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.
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, i.e., 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.
17 studies on the registry are indexed under Albinism; 8 are open to participants now.
Browse Albinism studies →This is the only study on the registry with William Gahl, M.D. as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For the portion of the protocol involving continuations of pirfenidone treatment, the criteria are simply previous enrollment in 97-HG-0085.
For enrollment in the new clinical trial, the inclusion criteria involve enrollment in protocol 95-HG-0193, "Clinical and Basic Investigations into Hermansky-Pudlak Syndrome". This itself requires a diagnosis of HPS based upon molecular grounds or the electron microscopic demonstration of deficiency of dense bodies. In addition, for protocol 97-HG-0085, patients must:
EXCLUSION CRITERIA
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subjects received pirfenidone 801 mg (3 pills of 267 mg each), three times daily.
Drug: Pirfenidone
Subjects received placebo (3 pills), three times daily.
Drug: Placebo
Treatment with pirfenidone 801 mg (3 pills of 267 mg each), three times daily.
Also known as: Deskar, Esbriet
Placebo (3 pills), three times daily.
Also known as: Inactive matching placebo
Change in Forced Vital Capacity (36 Months)
Change from baseline in the Forced Vital Capacity (FVC) measurement at 36 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).
Time frame: Measured at baseline and 36 months
Change in Forced Vital Capacity (12 Months)
Change from baseline in the Forced Vital Capacity (FVC) measurement at 12 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).
Time frame: Measured at baseline and 12 months
Change in Total Lung Capacity (36 Months)
Change from baseline in Total Lung Capacity (TLC) measured at 36 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
Time frame: Measured at baseline and 36 months
Change in Total Lung Capacity (12 Months)
Change from baseline in Total Lung Capacity (TLC) measured at 12 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
Time frame: Measured at baseline and 12 months
Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (36 Months)
Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 36 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
Time frame: Measured at baseline and 36 months
Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (12 Months)
Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 12 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
Time frame: Measured at baseline and 12 months
Change in 6 Minute Walk Test (36 Months)
Change from baseline of the 6 minute walk test (6MWT) at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
Time frame: Measured at baseline and 36 months
Change in 6 Minute Walk Test (12 Months)
Change from baseline of the 6 minute walk test (6MWT) at 12 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
Time frame: Measured at baseline and 12 months
Patients were enrolled at the NIH Clinical Center between September 2005 to March 2009.
| Milestone | Pirfenidone | Placebo |
|---|---|---|
| Started | 23 | 12 |
| Completed | 6 | 2 |
| Not completed | 17 | 10 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Withdrawal by subject | 3 | 1 |
| Withdrew: Study termination | 12 | 9 |
| Withdrew: Adverse event | 1 | 0 |
Change from baseline in the Forced Vital Capacity (FVC) measurement at 36 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Forced Vital Capacity (36 Months) | -23.52 ± 24.32 | -20.93 ± 25.59 |
Change from baseline in the Forced Vital Capacity (FVC) measurement at 12 months. FVC is the volume of air that can be forcibly blown out from the lungs after full inspiration. FVC is recorded as the percentage of predicted volume (predicted FVC volume is calculated based on subject's height, age, sex, and weight).
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Forced Vital Capacity (12 Months) | -7.27 ± 20.48 | -3.55 ± 21.33 |
Change from baseline in Total Lung Capacity (TLC) measured at 36 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Total Lung Capacity (36 Months) | -25.26 ± 24.42 | -22.9 ± 23.69 |
Change from baseline in Total Lung Capacity (TLC) measured at 12 months. TLC is the volume in the lungs at maximal inflation. TLC is recorded as the percentage of predicted volume based on subject's height, age, sex, and weight.
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Total Lung Capacity (12 Months) | -8.96 ± 21.03 | 0.53 ± 21.27 |
Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 36 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (36 Months) | -15.25 ± 29.89 | -14.93 ± 29.74 |
Change from baseline in adjusted Diffusing Capacity of the lung for carbon monoxide (DLCOa) measured at 12 months. DLCOa measures gas uptake during a single inspiration in a standard time, adjusted for subject's hemoglobin levels.
| % of predicted volume | Pirfenidone | Placebo |
|---|---|---|
| Change in Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (12 Months) | -3.11 ± 26.47 | -4.74 ± 25.97 |
Change from baseline of the 6 minute walk test (6MWT) at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
| meters | Pirfenidone | Placebo |
|---|---|---|
| Change in 6 Minute Walk Test (36 Months) | -232.86 ± 284.26 | -306.75 ± 314.69 |
Change from baseline of the 6 minute walk test (6MWT) at 12 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
| meters | Pirfenidone | Placebo |
|---|---|---|
| Change in 6 Minute Walk Test (12 Months) | -40.56 ± 192.66 | -17.21 ± 201.21 |
Collected over Adverse event data were collected over the entire period of the double-blind portion of the study, 4 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pirfenidone | — | 6/23 (26.1%) | 18/23 (78.3%) |
| Placebo | — | 2/12 (16.7%) | 9/12 (75%) |
| Event | Pirfenidone | Placebo |
|---|---|---|
| Chest painCardiac disorders | 2/23 | 0/12 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 2/23 | 1/12 |
| Blood creatinine phosphokinase increasedInvestigations | 1/23 | 1/12 |
| Deep vein thrombosisVascular disorders | 1/23 | 0/12 |
| HaematocheziaGastrointestinal disorders | 1/23 | 0/12 |
| Event | Pirfenidone | Placebo |
|---|---|---|
| DyspepsiaGastrointestinal disorders | 12/23 | 6/12 |
| DizzinessNervous system disorders | 4/23 | 0/12 |
| NauseaGastrointestinal disorders | 4/23 | 1/12 |
| Abdominal painGastrointestinal disorders | 0/23 | 2/12 |
| RashSkin and subcutaneous tissue disorders | 2/23 | 2/12 |
| VomitingGastrointestinal disorders | 0/23 | 2/12 |
| Chest painCardiac disorders | 3/23 | 1/12 |
| PalpitationsCardiac disorders | 3/23 | 0/12 |
| Drug eruptionImmune system disorders | 2/23 | 0/12 |
| FatigueGeneral disorders | 2/23 | 0/12 |
| Age, Categorical(Participants) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 22 | 12 | 34 |
| >=65 years | 1 | 0 | 1 |
| Age, Continuous(years) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Mean | 39.53 ± 11.00 | 43.97 ± 8.02 | 41.05 ± 10.18 |
| Sex: Female, Male(Participants) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Female | 15 | 6 | 21 |
| Male | 8 | 6 | 14 |
| Region of Enrollment(participants) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| United States | 23 | 12 | 35 |
| Forced Vital Capacity(% of predicted) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Mean | 72.77 ± 8.12 | 73.53 ± 10.09 | 73.03 ± 8.70 |
| Total Lung Capacity(% of predicted volume) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Mean | 73.84 ± 12.07 | 73.28 ± 10.09 | 73.65 ± 11.28 |
| Adjusted Diffusing Capacity of the Lung for Carbon Monoxide(% of predicted volume) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Mean | 67.82 ± 15.94 | 66.83 ± 16.60 | 67.48 ± 15.93 |
| 6 Minute Walk Test(meters) | Pirfenidone | Placebo | Total |
|---|---|---|---|
| Mean | 517.39 ± 112.79 | 526.87 ± 103.00 | 520.65 ± 107.94 |
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Studies of the drug tested here: Pirfenidone