FibrosisPhase 2NCT00001959

Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)

A Phase 2 study testing Pirfenidone in people with Fibrosis and Focal Glomerulosclerosis, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Fibrosis, Focal Glomerulosclerosis, Kidney Failure
What is being tested?: Pirfenidone
Type of treatment: Pill or oral medicine
How many people: 21 participants
Where: 1 siteUnited States
Study dates: Dec 1999to Oct 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults greater than or equal to 18 years of age.
Patients will provide informed consent.
Biopsy proven FSGS.
Glomerular filtration rate of at least 25 and no more than 80 ml/minute as assessed by the 4 variable Modification of diet in renal disease GFR equation.
At least 6 months of renal function data must be available prior to the patient's receiving pirfenidone, and renal function must show a rate of decline of greater than or equal to 0.4 ml/min/month during this baseline period.
Patients must have received no glucocorticoids, cyclophosphamide, mycophenolate or other immunosuppressive drugs for at least 2 months prior to the study period.

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Patients must have received no cyclosporin for at least 6 months prior to the study period.
Patients must have been taking an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a stable dose for at least 6 months, unless intolerant of both classes of medication.
Patients who are HIV seropositive will receive standard care for HIV disease (patients receiving immune-modulating therapy will be excluded).
Women with child-bearing potential must maintain an effective birth control regimen (oral contraceptive, intrauterine device, barrier plus spermicide).
Men will be advised that although Ames testing has been negative for any evidence of mutagenicity, they should consider use of contraceptives during the study period as well.

Who cannot join

Inability to give informed consent or cooperate with study.
Known intolerance to pirfenidone.
Evidence of FSGS associated with an additional primary or secondary glomerular disease (e.g. diabetes, membranous nephropathy, IgA nephropathy).
Recent (within 6 months) history of myocardial infarction.
History of peptic ulcer within 6 months.
History of cerebrovascular disease manifested by transient ischemic attack or cerebrovascular accident within 6 months.

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Pregnancy, breast feeding or inadequate birth control.
History of photosensitivity dermatitis.
Concurrent drug treatment with gemfibrozil, cyclosporin or erythromycin, potassium-sparing diuretics and other drugs which may potentiate hyperkalemia, or concurrent immunosuppresive medications.
Requirement for NSAID therapy.
Requirement for interleukin-2 therapy or other immune-modulating medication.
Existence of any other condition which would complicate the implementation or interpretation of the study.
Renal transplant.
Evidence of significant hepatic disease, as indicated by serum transaminases greater than 3 times upper limit of normal, protime greater than 2 seconds prolonged.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Pirfenidone in Focal Segmental Glomerulosclerosis:Phase II Study

This study will examine the effectiveness of the drug pirfenidone in treating focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine). About half of patients with FSGS eventually require kidney dialysis or transplant. Steroids, which are currently used to treat the disease, are effective in only a minority of patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in a very small percentage of patients and have serious side effects.

Patients with FSGS who wish to participate in this study will undergo pre-study evaluation with blood and urine tests. Patients must be on a stable dose of an ACE inhibitor (a drug that lowers blood pressure and reduces proteinuria) for at list 6 months before starting pirfenidone therapy. (Patients who are not already taking an ACE inhibitor will be started on the drug; those who cannot tolerate ACE inhibitors will be given a different drug.) Patients with elevated cholesterol will take a cholesterol-lowering drug. A diet containing approximately 1 gram of protein per kilogram of body weight per day will be recommended.

Patients will take pirfenidone by mouth 3 times a day for 12 months. Blood and urine will be tested once a month, either at NIH or by the patient's local kidney specialist. They will collect two 24-hour urine samples at the beginning of the treatment period, at 2-month intervals throughout the study, and at a 6-month follow-up. Patients will also be asked to give three to five tubes of blood and urine samples for analysis during the study.

In animal studies, pirfenidone improved kidney function and proteinuria and reduced kidney scarring in rats with a disease similar to FSGS. In human studies, pirfenidone improved breathing and survival in patients with lung fibrosis.

Read the detailed description

The objective of this pilot phase II trial is to evaluate the ability of pirfenidone, a novel anti-fibrotic agent, to reduce the proteinuria and slow the rate of progression of renal insufficiency in patients with focal segmental glomerulosclerosis (FSGS). We will enroll 25 patients with renal biopsy proven FSGS and evidence of impaired renal function (glomerular filtration rate, GFR, of 10-80 ml/min; after 1/02 must have GFR greater than 25 ml/min) as assessed by the 4 variable Modification of Diet in Renal Disease equation. As standard of care therapy, all patients will also receive angiotensin converting enzyme inhibitor (ACEI) therapy, and will receive an HMG Co-A reductase inhibitor drug if hypercholesterolemic. Preliminary evaluation will assure that the patients meet the study requirements, and an evaluation period will be used to ensure that patients are on maximal conservative therapy prior to the baseline period. Patients will receive treatment with pirfenidone daily, with dose adjusted for body weight and level of kidney function. The primary end point will be the decrease glomerular filtration as a marker of glomerular injury; reduction in proteinuria will be a secondary end-point. If the pilot study suggests this drug delays progression of renal insufficiency or reduces proteinuria in patients with FSGS, we will proceed with a large scale randomized, placebo-controlled study.

Conditions: Fibrosis, Focal Glomerulosclerosis, Kidney Failure, Nephrotic Syndrome, Proteinuria
Being tested: Pirfenidone
Keywords: Fibrosis, Nephrotic Syndrome, Proteinuria, Renal Failure, TGF-Beta, Focal Segmental Glomerulosclerosis, FSGS
Medical subject headings: Fibrosis, Glomerulosclerosis, Focal Segmental, Renal Insufficiency, Nephrotic Syndrome, Proteinuria, Camurati-Engelmann Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PirfenidoneDrug
During the study drug period of 12 months, patients will receive oral pirfenidone daily. For patients whose initial renal function is 50-80 ml/min as assessed by the MDRD equation, the initial pirfenidone dosage will be calculated at 40 mg/kg/d, with a maximum dose of 800 mg TID. For patients whose initial renal function is 30-50 ml/min, the initial dose will be 30 mg/kg/d. For patients whose initial renal function is between 15 and 30 ml/min, the initial dose will be 20 mg/kg/d.

What is being measured

The primary outcome is the main question the study is designed to answer.

Decrease in GFR During Treatment Period
Measured: 12 months from baseline

Secondary outcomes (2)

Proteinuria After Treatment
Measured: 12 months from baseline
Proportion of Patients With Positive Change in GFR
Measured: 12 months from baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 1999Oct 2008

First posted19 Jan 2000 (estimated)
Study startDec 1999
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for FibrosisStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00001959
Sponsor's protocol ID: 000042
Other IDs: 00-DK-0042
Status last verified: Apr 2012
First submitted: 18 Jan 2000
Last updated: 26 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Abbate M, Zoja C, Rottoli D, Corna D, Perico N, Bertani T, Remuzzi G. Antiproteinuric therapy while preventing the abnormal protein traffic in proximal tubule abrogates protein- and complement-dependent interstitial inflammation in experimental renal disease. J Am Soc Nephrol. 1999 Apr;10(4):804-13. doi: 10.1681/ASN.V104804.
PubMed 10203365
Bodi I, Kimmel PL, Abraham AA, Svetkey LP, Klotman PE, Kopp JB. Renal TGF-beta in HIV-associated kidney diseases. Kidney Int. 1997 May;51(5):1568-77. doi: 10.1038/ki.1997.215.
PubMed 9150474
Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994 Nov 10;331(19):1286-92. doi: 10.1056/NEJM199411103311907. No abstract available.
PubMed 7935686

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pirfenidone in Focal Segmental Glomerulosclerosis:Phase II Study
ClinicalTrials.gov ID: NCT00001959
Acronym / sponsor ID: 000042
Conditions: Fibrosis, Focal Glomerulosclerosis, Kidney Failure, Nephrotic Syndrome, Proteinuria
Keywords: Fibrosis, Nephrotic Syndrome, Proteinuria, Renal Failure, TGF-Beta, Focal Segmental Glomerulosclerosis, FSGS
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Study start: Dec 1999
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 19 Jan 2000 (estimated)
Results: Posted 1 Jun 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Key exclusion criteria (14 listed)

Inability to give informed consent or cooperate with study.
Known intolerance to pirfenidone.
Evidence of FSGS associated with an additional primary or secondary glomerular disease (e.g. diabetes, membranous nephropathy, IgA nephropathy).
Recent (within 6 months) history of myocardial infarction.
History of peptic ulcer within 6 months.

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
PirfenidoneDuring the study drug period of 12 months, patients will receive oral pirfenidone daily. For patients whose initial renal function is 50-80 ml/min as assessed by the MDRD equation, the initial pirfenidone dosage will be calculated at 40 mg/kg/d, with a maximum dose of 800 mg TID. For patients whose initial renal function is 30-50 ml/min, the initial dose will be 30 mg/kg/d. For patients whose initial renal function is between 15 and 30 ml/min, the initial dose will be 20 mg/kg/d.	Drug	–

Primary outcome

Decrease in GFR During Treatment Period
Time frame: 12 months from baseline

2 secondary outcomes

Proteinuria After Treatment
Time frame: 12 months from baseline
Proportion of Patients With Positive Change in GFR
Time frame: 12 months from baseline

Results and safety

Results posted to the registry on 1 Jun 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pirfenidone	21	18

Primary outcome: Decrease in GFR During Treatment Period

Time frame: 12 months from baseline. Mean (Inter-Quartile Range). Unit: ml/min/1.73 m2

Measure	Pirfenidone n = 18
Value	-0.45 (-0.78 to -0.16)

Pirfenidone: p <0.01, Wilcoxon (Mann-Whitney)

Population analysed: ITT

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 60 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pirfenidone	3 of 21 (14.3%)	16 of 21 (76.2%)	Not reported

Limitations and caveats (from the sponsor): No control group, measurement imprecision, results may not applicable to all patients with FSGS, needs histologic evidence to support our findings, Optimal dosage needs to be identified.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 10203365Abbate M, Zoja C, Rottoli D, Corna D, Perico N, Bertani T, Remuzzi G. Antiproteinuric therapy while preventing the abnormal protein traffic in proximal tubule abrogates protein- and complement-dependent interstitial inflammation in experimental renal disease. J Am Soc Nephrol. 1999 Apr;10(4):804-13. doi: 10.1681/ASN.V104804.
Background: PubMed 9150474Bodi I, Kimmel PL, Abraham AA, Svetkey LP, Klotman PE, Kopp JB. Renal TGF-beta in HIV-associated kidney diseases. Kidney Int. 1997 May;51(5):1568-77. doi: 10.1038/ki.1997.215.
Background: PubMed 7935686Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994 Nov 10;331(19):1286-92. doi: 10.1056/NEJM199411103311907. No abstract available.
NIH Clinical Center Detailed Web PageLink 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.

The record lists no contact. Use the official record to reach the sponsor.

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 Pirfenidone in people with Fibrosis and Focal Glomerulosclerosis, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 14 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: finished, as of the sponsor's last update on 26 May 2014. 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?

Yes. Results are posted in the registry (first posted 1 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Decrease in GFR During Treatment Period (time frame: 12 months from baseline). 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 NCT00001959, which also lists 3 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 26 May 2014.