Hydroxychloroquine as Steroid-Sparing Agent in Pulmonary Sarcoidosis (HySSAS).

NCT02200146 | Completed Phase 3 DMC

• 1 other identifier: HySSAS-FARM639KLZ
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is determining the non-inferiority in the overall success rate and the safety for a combination therapy with hydroxychloroquine plus low dose glucocorticoids compared to that for high dose glucocorticoids at 3 and 9 months in patients with pulmonary sarcoidosis.

Conditions

Pulmonary Sarcoidosis

Keywords

sarcoidosis; treatment; lung; glucocorticoids; hydroxychloroquine

Outcome Measures

Primary Outcomes (2)

• The primary EFFICACY measure is the per-subject overall success rate at the 3 month visit. Overall response is defined as a combined radiographic and clinical responses.

  Subjects is considered clinically cured at the 3 month visit if they will have radiographic success (determined if Chest X-Ray is resolved or improved compared to the baseline; improvement was assessed if there were reduction in hilar adenopathies, less pulmonary involvement, changing in radiographic stage) PLUS a change in at least one of the followings: symptoms (determined by dyspnea or cough index score decrease compared to the baseline), and/or functional improvement (determined by an increase in % of predicted Forced Vital Capacity and/or increase in % of predicted Single-Breath Diffusion capacity of Lung for Carbon monoxide DLCO-SB compared to the baseline), and/or increase in resting Partial pressure of Oxygen in the artery blood (PaO2), and/or worst oxygen saturation increase during 6 Minute Walk Test (6MWT) and/or increase in distance walked at 6MWT, compared to the baseline

  Baseline- After 3 months of treatment

• The primary SAFETY endpoint is the percent change in lumbar spine (L1-L4) bone mineral density from baseline to month 9 as measured by Dual energy X-ray Absorptiometry (DXA)

  Baseline - After 9 months of treatment

Secondary Outcomes (6)

• Secondary EFFICACY endpoint was the change from baseline in radiographic success rate after 9 month of therapy (measured by High Resolution Chest Tomography HRCT)

  Baseline- After 9 months of therapy

• Secondary SAFETY endpoint was the change from baseline in Body Mass Index

  Baseline - After 3, 6 and 9 months

• Secondary SAFETY endpoint was the change from baseline in HbA1c

  At 3, 6 and 9 months of therapy

• Secondary SAFETY endpoint was the change from baseline in clinical laboratory tests (including inflammatory markers)

  At 3, 6 and 9 months of therapy

• Secondary SAFETY endpoint was the change from baseline in bone turnover markers and mineral metabolism

  At months 3 and 9 from the start of therapy

Study Arms (2)

Prednisone

ACTIVE COMPARATOR

Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.

Drug: Prednisone

Hydroxychloroquine + Prednisone

EXPERIMENTAL

Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.

Drug: Hydroxychloroquine + Prednisone

Interventions

Prednisone DRUG

Prednisone per os 0,5 mg/kg/die once/day for 3 months. After 3 months, between responders, prednisone was slowly tapered (5 mg/week maintaining the new reduced dose for one week) to 0,2 mg/kg/die for further 6 months.

Prednisone

Hydroxychloroquine + Prednisone DRUG

Hydroxychloroquine per os 200 mg/die (or adjusted for body weight if less than 61 kg), twice/day + prednisone 0,15 mg/kg per os daily, once/day for 3 months, than for further 6 months between responders.

Hydroxychloroquine + Prednisone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients between 18 and 70 years
• parenchymal pulmonary involvement at Chest X-Ray (CXR) AND one of the follows: physiologic abnormalities on pulmonary function testing and/or respiratory symptoms, and/or exercise-induced abnormalities.

You may not qualify if:

• Unable to understand protocol and to sign informed consent or not suitable candidate to comply with the requirements of this study, in the opinion of the investigator
• Cardiac and neurological sarcoidosis or any other organ involvement
• End stage lung disease at high-resolution computed tomography (HRCT)
• Clinical evidence of active infection
• Documented exposure to beryllium
• Patients with Forced Expiratory Volume at one second (FEV1) changes after salbutamol inhalation ≥20%
• Comorbidity: advanced liver cirrhosis or abnormal liver function, unstable cardiac disease, moderate to severe renal insufficiency, poorly controlled diabetes
• Pregnancy or lactation
• A tuberculin skin test (5 I.U.) more than 5 mm
• Psoriasis
• Homozygous glucose-6-phosphatase deficiency
• Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives
• Visual field changes attributable to 4-aminoquinolines
• Concomitant therapies: any patient enrolled in the study must be off all prohibited medications at least 4 weeks before screening. Once patients completed the washout period, they may enter the screening period that may last up to 30 days
• Previous therapies: any patient enrolled must be off all medications for sarcoidosis at least 4 weeks before screening.

Sponsors & Collaborators

• University of Milano Bicocca: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

Università degli Studi di Milano - Bicocca

Milan, Milano, 20126, Italy

Location

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

Prednisone; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alberto Pesci

  Università Milano Bicocca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2014
• First Posted: July 25, 2014
• Study Start: March 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 25, 2014

Record last verified: 2014-07

Locations

IT (1)