Pirfenidone in the Chronic Hypersensitivity Pneumonitis Treatment

NCT ID: NCT02496182

Last Updated: 2015-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-01-31

Brief Summary

The Chronic Hypersensitivity Pneumonitis (HP), is an inflammatory disease who has an evolution to develop progressive interstitial fibrosis, who cause the death of the patient. Actually HP has been treated with Prednisone and occasionally with Azathioprine, but unfortunately the treatment with these drugs have not an effective result to treat the interstitial fibrosis.

Pirfenidone has been studied over the world for the treatment of Fibrotic diseases, with positive results, and due to the Pirfenidone mechanism of action has anti-inflammatory and anti-fibrotic properties, the investigators propose to evaluate the addition of Pirfenidone to the actual treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis.

Detailed Description

The Chronic Hypersensitivity Pneumonitis (HP), is a complex syndrome due to a exaggerated immune response caused by inhalation of foreign substances, such as molds, dusts, and organic particles, causing alveoli inflammation and in the chronic forms the disease has high rate of mortality, due to the big number of patients who develop progressive interstitial fibrosis and eventually they curse with respiratory insufficiency who cause the death of the patient.

Pirfenidone has been studied over the world for the treatment of Idiophatic Pulmonary Fibrosis (IPF), disease who constitute the most aggressive of the fibrotic diseases of the lung. Additionally Pirfenidone has been showed potential results in the treatment of fibrotic diseases in other organs, as Liver, Kidney, Hearth, etc. Pirfenidone has been described as a modulator of the fibrotic process due to his action over TGF-beta and MMP´s and also has into-inflammatory actions acting over TNF-alfa and IL-1 and IL-6.

Actually HP has been treated with Prednisone and occasionally with Azathioprine, but a high number of patients will develop irreversibly to a interstitial fibrosis with pulmonary parenchyma destruction. Unfortunately the investigators have not an effective treatment for this cases. Due to the positive results obtained with Pirfenidone in the treatment of IPF and other kind of organ fibrosis, the investigators propose to evaluate the addition of Pirfenidone to the treatment with Prednisone and Azathioprine in the treatment of patients with Pulmonary Fibrosis secondary to a Chronic Hypersensitivity Pneumonitis.

Conditions

Alveolitis Extrinsic Allergic; Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Conventional treatment (Prednisone 0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Placebo tablet 2 times at day.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet only with the excipients of the Pirfenidone tablet

Pirfenidone 1800 mg

Conventional treatment (0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Pirfenidone long release tablet 900 mg 2 times at day, starting with 600 mg at day

Group Type: EXPERIMENTAL

Pirfenidone

Intervention Type: DRUG

Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1800 mg

Pirfenidone 1200 mg

Conventional treatment (0.5 mg/kg/day for 4 weeks, then 0.25 mg/Kg/day for 8 weeks and maintenance dosage of 0.125 mg/Kg/day plus Azathioprine 2-3 mg/kg/day with a maximal dosage of 150 mg/day starting with 25-50 mg/day increasing gradually until day 14 with maximal dosage) plus Pirfenidone long release tablet 600 mg 2 times at day starting with 600 mg at day

Group Type: EXPERIMENTAL

Pirfenidone

Intervention Type: DRUG

Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1200 mg

Interventions

Placebo

Placebo tablet only with the excipients of the Pirfenidone tablet

Intervention Type: DRUG

Pirfenidone

Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1800 mg

Intervention Type: DRUG

Pirfenidone

Conventional Treatment (Prednisone+Azathioprine) plus Pirfenidone 1200 mg

Intervention Type: DRUG

Other Intervention Names

Excipient Tablet; Kitoscell LP; KitosCell LP

Eligibility Criteria

Inclusion Criteria

• Chronic Hypersensitivity pneumonitis with recent diagnosis confirmed by HRT with or without biopsy
• Acceptation with signed informed consent

Exclusion Criteria

• No confirmed diagnosis
• Patients with peptic ulcer
• Pregnancy or breast feeding period
• Clinical signs of active infection
• History of severe Hepatic disease
• History of severe Kidney disease, who requires some kind of dialysis
• History of inestable cardiopathy
• History of alcohol or drugs abuse
• Bronchial hyperactivity or History of asthma or EPOC
• Smoking habit 3 months before the starting or patient who decline suspend the smoking habit during the study
• Patient with impossibility to make spirometry or who can not walk
• Use of Immunosuppressants, cytotoxic agents, cytosine modulators or receptor antagonist, fluvoxamine or daily use of sildenafil.
• Patients who not accept sign the informed consent

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Medifarma, S. A. de C. V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Instituto Nacional de Enfermedades Respiratorias

Mexico City, Mexico City, Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

Pedro Pena, MD

Role: CONTACT

pedropena@grupomedifarma.com

+52191971972

Jarod Escobar, MD

Role: CONTACT

jarodescobar@cellpharma.com

+525515764477

Facility Contacts

Heidegger Mateos, MD

Role: primary

+5255 5487 1771

Pedro Pena, MD

Role: backup

pedropena@grupomedifarma.com

+5215591971972

References

Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y; HP Study Group. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):952-8. doi: 10.1164/rccm.200301-137OC. Epub 2003 Jul 3.

Reference Type: BACKGROUND

PMID: 12842854 (View on PubMed)

Selman M. Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med. 2004 Sep;25(3):531-47, vi. doi: 10.1016/j.ccm.2004.04.001.

Reference Type: BACKGROUND

PMID: 15331190 (View on PubMed)

Gaxiola M, Buendia-Roldan I, Mejia M, Carrillo G, Estrada A, Navarro MC, Rojas-Serrano J, Selman M. Morphologic diversity of chronic pigeon breeder's disease: clinical features and survival. Respir Med. 2011 Apr;105(4):608-14. doi: 10.1016/j.rmed.2010.11.026. Epub 2010 Dec 16.

Reference Type: BACKGROUND

PMID: 21167698 (View on PubMed)

Macias-Barragan J, Sandoval-Rodriguez A, Navarro-Partida J, Armendariz-Borunda J. The multifaceted role of pirfenidone and its novel targets. Fibrogenesis Tissue Repair. 2010 Sep 1;3:16. doi: 10.1186/1755-1536-3-16.

Reference Type: BACKGROUND

PMID: 20809935 (View on PubMed)

Selman M, Pardo A, Richeldi L, Cerri S. Emerging drugs for idiopathic pulmonary fibrosis. Expert Opin Emerg Drugs. 2011 Jun;16(2):341-62. doi: 10.1517/14728214.2011.565049. Epub 2011 Mar 17.

Reference Type: BACKGROUND

PMID: 21410428 (View on PubMed)

Schaefer CJ, Ruhrmund DW, Pan L, Seiwert SD, Kossen K. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev. 2011 Jun;20(120):85-97. doi: 10.1183/09059180.00001111.

Reference Type: BACKGROUND

PMID: 21632796 (View on PubMed)

Mateos-Toledo H, Mejia-Avila M, Rodriguez-Barreto O, Mejia-Hurtado JG, Rojas-Serrano J, Estrada A, Castillo-Pedroza J, Castillo-Castillo K, Gaxiola M, Buendia-Roldan I, Selman M. An Open-label Study With Pirfenidone on Chronic Hypersensitivity Pneumonitis. Arch Bronconeumol (Engl Ed). 2020 Mar;56(3):163-169. doi: 10.1016/j.arbres.2019.08.019. Epub 2019 Nov 26. English, Spanish.

Reference Type: DERIVED

PMID: 31784348 (View on PubMed)

Other Identifiers

C34-11

Identifier Type: -

Identifier Source: org_study_id