Hermansky Pudlak SyndromePhase 2PEARLNCT04193592
Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
A Phase 2 study testing Pirfenidone in people with Hermansky Pudlak Syndrome and Interstitial Lung Disease, run by Jesse Roman at 2 sites in 2 countries.
Trial summary
This research study will explore the safety and efficacy of the drug, pirfenidone, in patients with a diagnosis of Hermansky-Pudlak Syndrome (HPS) who have an associated interstitial lung disease (ILD) over a planned period of 56 weeks. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hermansky Pudlak Syndrome, Interstitial Lung Disease
- What is being tested?
- Pirfenidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Dec 2019to 31 Dec 2022
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Probable or definite diagnosis of HPS based on confirmed genetic mutation or clinical picture characterized by oculo-cutaneous albinism, bleeding disorder, and possible colitis and ILD.
- Diagnosis of ILD supported by clinically indicated HRCT prior to Screening, and presence of fibrotic abnormality affecting more than 5% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on Screening
- No features supporting an alternative diagnosis (e.g., infection)
- Change in pre-bronchodilator FVC (measured in liters) between Screening (Visit 1) and
- Baseline (Visit 2) must be a < 10% relative difference, calculated as:
- 100%[absolute value (Screening FVC - Baseline FVC)/Screening FVC
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- Stable dose (at least three months at the time of Screening) of corticosteroids.
- No cytotoxic, immunosuppresive agents, cytokine-modulating, or receptor antagonists agents are allowed (including but not limited to azathioprine, cyclophosphamide, cyclosporine, etanercept, iloprost, infliximab, methotrexate, mycophenolate mofetil, nintedanib, tacrolimus, tetrathiomolybdate, TNF-α inhibitors, rituximab, abatacept, tofacitintib, tociluzimab).
- Able to understand and sign a written informed consent form
Who cannot join
- Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
- Cigarette smoking within 3 months of Screening or unwilling to avoid tobacco products throughout the study
- History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
- Concurrent presence of other interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer
- Concurrent presence of other pleuropulmonary manifestations inconsistent with HPS- ILD
- Presence of pleural effusion occupying more than 10% of the hemithorax on Screening HRCT
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- Clinical diagnosis of a connective tissue disease or overlap syndrome (including but not limited to rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus)
- Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principle investigator
- Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
- Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma in situ.
- History of severe hepatic impairment or end-stage liver disease
- History of end-stage renal disease requiring dialysis
- History of unstable or deteriorating cardiac or disease, myocardial infarction within the previous year, heart failure within the last 3 years, or cardiac arrhythmia requiring drug therapy
- Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the 52 weeks of treatment.
- A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
- Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
- For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 118 days after the last dose of pirfenidone.
- Men must refrain from donating sperm during this same period.
- Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site including pirfenidone, at the time of Screening
- History of alcohol or substance abuse in the past 2 years, at the time of Screening
- Family or personal history of long QT syndrome
- Any of the following liver function test criteria above specified limits:
- Total bilirubin above the upper limit of normal (ULN), excluding patients with Gilbert's syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 × ULN
- Creatinine clearance (CrCl <30) mL/min, calculated using the Cockcroft-Gault formula
- Electrocardiogram (ECG) with a QTcB interval >500 msec at Screening
- Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment
- Use of any of the following therapies within 28 days before Screening:
- Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site
- Fluvoxamine
- Sildenafil (daily use). Note: intermittent use for erectile dysfunction is allowed
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Tamra Perez, 215-955-9181, tamra.perez@jefferson.edu
Jesse Roman, MD
Puerto Rico1 site
Mayaguez Medical Center
Mayagüez, 00680
Rosa Roman, MD, 7874676080
Rosa Roman, MD
About this study
Official title: Pirfenidone in the Treatment of Hermansky Pudlak Syndrome (HPS) - Related Interstitial Lung Disease (ILD)
This research study will explore the safety and efficacy of the drug, pirfenidone, in patients with a diagnosis of Hermansky-Pudlak Syndrome (HPS) who have an associated interstitial lung disease (ILD) over a planned period of 56 weeks.
Read the detailed description
An open-label clinical study designed to evaluate the efficacy and safety of administering pirfeniodne for 52 weeks to subjects with HPS-ILD. Patients meeting the eligibility criteria without contraindications for the study will be provided pirfenidone 2403 mg/day. Efficacy will be evaluated through interval testing of pulmonary function tests, patient reported outcomes, adverse events and survival. Safety will be assessed by determining adverse events, hospitalizations, and all-cause mortality.
- Being tested
- Pirfenidone
- Keywords
- safety, efficacy, patient reported outcomes
- Medical subject headings
- Hermanski-Pudlak Syndrome, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
Also called Esbriet
Pirfenidone will be titrated over 14 days, as tolerated, to the full dose of 2403 mg per day, as follows: Days 1 - 7: one capsule TID; Days 8 - 14: two capsules TID; Days 15 to week 52: three capsules TID. Dose may be reduced to manage an adverse event.
| Study group | Role | What they receive |
|---|---|---|
| Oral Pirfenidone 2403 mg per day | Experimental | Enrolled subjects will receive oral pirfenidone 801 mg taken three times a day. Pirfenidone will be supplied in 267 mg capsules. Receives: Drug: Pirfenidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Forced Vital Capacity (FVC)
The incidence of decline in percent predicted FVC of 10 % or greater from baseline measured at 6 and 12 months
Measured: baseline, 6 months, 12 months
Secondary outcomes (4)
Change in Forced Vital Capacity (FVC)
- The Incidence of decline from baseline in percent predicted FVC of 10% or greater during the 52 week treatment period.
Measured: week 52
Change in Diffusion Capacity (DLCO)
- The Incidence of decline from baseline in percent predicted DLCO of 15% or greater during the 52 week treatment period.
Measured: week 52
Incidence of Treatment Emergent Adverse Events
- The number of participants with and number of treatment emergent adverse events reported by the participant will be collected.
Measured: week 52
Incidence of Treatment Emergent Serious Adverse Events
- The number of participants with and number of treatment-emergent serious adverse events reported by the participants will be collected.
Measured: week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start1 Dec 2019 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hermansky Pudlak SyndromeStudies of the same condition, open and under way.
- 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
- Model description
- open label drug
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jesse Roman
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor-investigator, Jesse Roman, Thomas Jefferson University
- Investigators
- Jesse Roman, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04193592
- Sponsor's protocol ID
- 14172/2019
- Acronym
- PEARL
- Status last verified
- Dec 2019
- First submitted
- 6 Nov 2019
- Last updated
- 10 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pirfenidone in the Treatment of Hermansky Pudlak Syndrome (HPS) - Related Interstitial Lung Disease (ILD)
- ClinicalTrials.gov ID
- NCT04193592
- Acronym / sponsor ID
- PEARL / 14172/2019
- Keywords
- safety, efficacy, patient reported outcomes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Jesse RomanUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 1 Dec 2019 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 10 Dec 2019 (actual)
- 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.
This research study will explore the safety and efficacy of the drug, pirfenidone, in patients with a diagnosis of Hermansky-Pudlak Syndrome (HPS) who have an associated interstitial lung disease (ILD) over a planned period of 56 weeks.
Detailed description
An open-label clinical study designed to evaluate the efficacy and safety of administering pirfeniodne for 52 weeks to subjects with HPS-ILD. Patients meeting the eligibility criteria without contraindications for the study will be provided pirfenidone 2403 mg/day. Efficacy will be evaluated through interval testing of pulmonary function tests, patient reported outcomes, adverse events and survival. Safety will be assessed by determining adverse events, hospitalizations, and all-cause mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open label drug
| Arm | Type | Receives |
|---|---|---|
| Oral Pirfenidone 2403 mg per day | Experimental | Drug: PirfenidoneEnrolled subjects will receive oral pirfenidone 801 mg taken three times a day. Pirfenidone will be supplied in 267 mg capsules. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Probable or definite diagnosis of HPS based on confirmed genetic mutation or clinical picture characterized by oculo-cutaneous albinism, bleeding disorder, and possible colitis and ILD.
- Diagnosis of ILD supported by clinically indicated HRCT prior to Screening, and presence of fibrotic abnormality affecting more than 5% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on Screening
- No features supporting an alternative diagnosis (e.g., infection)
- Change in pre-bronchodilator FVC (measured in liters) between Screening (Visit 1) and
- 100%[absolute value (Screening FVC - Baseline FVC)/Screening FVC
Key exclusion criteria (33 listed)
- Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
- Cigarette smoking within 3 months of Screening or unwilling to avoid tobacco products throughout the study
- History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
- Concurrent presence of other interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer
- Concurrent presence of other pleuropulmonary manifestations inconsistent with HPS- ILD
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 |
|---|---|---|
| PirfenidoneAlso: EsbrietPirfenidone will be titrated over 14 days, as tolerated, to the full dose of 2403 mg per day, as follows: Days 1 - 7: one capsule TID; Days 8 - 14: two capsules TID; Days 15 to week 52: three capsules TID. Dose may be reduced to manage an adverse event. | Drug | Oral Pirfenidone 2403 mg per day |
Primary outcome
Change in Forced Vital Capacity (FVC)
Time frame: baseline, 6 months, 12 months
The incidence of decline in percent predicted FVC of 10 % or greater from baseline measured at 6 and 12 months
4 secondary outcomes
Change in Forced Vital Capacity (FVC)
Time frame: week 52
Change in Diffusion Capacity (DLCO)
Time frame: week 52
Incidence of Treatment Emergent Adverse Events
Time frame: week 52
Incidence of Treatment Emergent Serious Adverse Events
Time frame: week 52
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2019.
- Individual participant dataSharing planned: No
Related trials for Hermansky Pudlak Syndrome
RecruitingObservational study
Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
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Active, not recruitingObservational study
Analysis of Specimens From Individuals With Pulmonary Fibrosis
Pulmonary Fibrosis, Healthy Volunteers
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
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.
Jesse Roman, MD principal investigator
Thomas Jefferson University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pirfenidone in people with Hermansky Pudlak Syndrome and Interstitial Lung Disease, run by Jesse Roman at 2 sites in 2 countries.
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 9 inclusion and 33 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 10 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Puerto Rico. 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?
Contact Tamra Perez, BSN (1-215-955-9181, tamra.perez@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Forced Vital Capacity (FVC) (time frame: baseline, 6 months, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2019.