Cyclosporine A in the TReatment of Interstitial Pneumonitis Associated With Sjogren's Syndrome

NCT ID: NCT02370550

Last Updated: 2020-05-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2021-12-31

Brief Summary

The purpose of this large multicenter, randomized, double-blinded, controlled clinical study is to investigate the efficacy and safety of Cyclosporin A for primary Sjogren's syndrome associated pneumonitis(pSS-IP), which has important implications for the establishment of standardized diagnosis and treatment of pSS-IP.

Conditions

Sjogren's Syndrome

Study Design

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

Study Groups

Cyclosporin A(CsA)+glucocorticoid

A. The efficacy/safety are evaluated at V3, V4, V5 and V6, and the treatment is adjusted accordingly. Patients who experienced treatment failure (FVC absolute decrease \>15% of predicted values after 4 weeks of treatment) are suggested to switch to intravenous glucocorticoid + cyclophosphamide(CYC) 0.5-1 g/m2 every 4 weeks as the rescue therapy after unblinding, and continue to complete the subsequent follow-up. Each patient can only have one chance to be rescued. Patients who experience a second treatment failure should be withdrawn from the trial and be given empirical treatment. Patients who did not experience treatment failure continued to receive current treatment. B. For subjects with aggravated shortness of breath and dyspnea in between of two consecutive visits, the investigators should decide whether a visit should be increased to complete subsequent examinations.

Group Type: EXPERIMENTAL

Cyclosporin A

Intervention Type: DRUG

CsA 2-3 mg/kg/d, BID PO

Prednisone

Intervention Type: DRUG

Prednisone 0.5mg/kg/d QD PO starting at Week 0. After 2-4 weeks, the initial dose is gradually tapered by 2.5 mg each week until a maintenance dosage of 5-7.5 mg/d through week 52 (visit 6). The initial and maintenance doses are determined by the investigators of each center depending on the patients.

Calcium carbonate D

Intervention Type: DRUG

Calcium carbonate D 600 mg, QD PO

placebo+glucocorticoid

A. The efficacy/safety are evaluated at V3, V4, V5 and V6, and the treatment is adjusted accordingly. Patients who experienced treatment failure are suggested to switch to glucocorticoid + CsA 2-3mg/kg/d, BID as the rescue therapy, and continue to complete the subsequent follow-up. Each patient can only have one chance to be rescued. Patients who did not experience treatment failure continued to receive current treatment. B. For subjects with aggravated shortness of breath and dyspnea in between of two consecutive visits, the investigators in each center should decide whether a visit should be increased.

Group Type: PLACEBO_COMPARATOR

Prednisone

Intervention Type: DRUG

Prednisone 0.5mg/kg/d QD PO starting at Week 0. After 2-4 weeks, the initial dose is gradually tapered by 2.5 mg each week until a maintenance dosage of 5-7.5 mg/d through week 52 (visit 6). The initial and maintenance doses are determined by the investigators of each center depending on the patients.

Placebo

Intervention Type: DRUG

Placebo tablet 2-3 mg/kg/d, BID PO

Calcium carbonate D

Intervention Type: DRUG

Calcium carbonate D 600 mg, QD PO

Interventions

Cyclosporin A

CsA 2-3 mg/kg/d, BID PO

Intervention Type: DRUG

Prednisone

Prednisone 0.5mg/kg/d QD PO starting at Week 0. After 2-4 weeks, the initial dose is gradually tapered by 2.5 mg each week until a maintenance dosage of 5-7.5 mg/d through week 52 (visit 6). The initial and maintenance doses are determined by the investigators of each center depending on the patients.

Intervention Type: DRUG

Placebo

Placebo tablet 2-3 mg/kg/d, BID PO

Intervention Type: DRUG

Calcium carbonate D

Calcium carbonate D 600 mg, QD PO

Intervention Type: DRUG

Other Intervention Names

Cyclosporin A Capsules, CsA soft capsules 25 mg, Hangzhou China-US East China pharmaceutical Co., Ltd.

Eligibility Criteria

Inclusion Criteria

• Patients meeting the 2002 or 2012 pSS criteria;
• Patients meeting the diagnostic criteria of interstitial pneumonitis(IP);
• Patients with exertional dyspnea consistent with grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index;
• Pulmonary function test: patients with percentages of forced vital capacity (FVC) to predicted values≥45%, percentage of diffusing capacity of carbon monoxide (DLco) to predicted values≥30%, forced expiratory volume in one second (FEV1) / FVC> 65%;
• For patients who received oral glucocorticoid, the doses should be no more than 10 mg/d (or equivalent amount of other types of glucocorticoids);
• Patients who had not received any prior treatment with immunosuppressants (including but not limited to CYC, CsA, azathioprine(AZA), tacrolimus(FK-506), methotrexate, leflunomide, etc.) or had discontinued the therapy above for at least 3 months; for patients who received hydrochloroquine(HCQ), the doses should be stabilized for at least 3 months;
• Patients who had not received any prior treatment with biological agents, including but not limited to rituximab, infliximab, adalimumab, etanercept, etc., or had discontinued therapy for at least three months;
• For patients who had prior treatment with N-acetylcysteine, the doses of above drugs should be stabilized for at least 3 months;
• The women of reproductive age who had a negative urine pregnancy test. The women and men of reproductive age must receive effective contraceptive measures from the screening period to last administration of drugs;
• Patients who were able to read, to understand and to sign informed consent.

Exclusion Criteria

• Patients with acute exacerbation of IP(AEIP);
• Arterial blood gas analysis showed respiratory failure;
• Patients with lung diseases other than IP:

1. Patients with severe pulmonary hypertension who require specific treatments assessed by the rheumatology and immunology experts in various clinical centers;

2. Patients with a history of smoking within the last 6 months or current smokers;

3. Patients with other serious lung diseases, such as lung tumor or active pulmonary infection;

4. Lung biopsy, alveolar lavage or high-resolution computerized tomography (HRCT) suggested serious lung diseases other than IP;

• Patients with other rheumatic autoimmune diseases, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, inflammatory myopathy, systemic sclerosis, primary biliary cirrhosis, etc.;
• Patients with serious heart, liver, kidney diseases, hematologic and/ or endocrine diseases:

1. Heart diseases: decompensated heart failure or refractory hypertension; clinically important abnormal ECG that may lead to unacceptable risks to enrolled patients at screening;

2. Liver function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2 times the upper limit of normal (ULN);

3. Renal function: renal tubular and/or interstitial diseases, renal insufficiency: serum creatinine≥2 ULN or glomerular filtration rate (eGFR) <90 ml/min/1.73 m2;

4. White blood cell (WBC) count <3 ×109/L and/or hemoglobin (Hb) <100 g/L and/or platelet (PLT) count <80×109 /L;

5. Other serious diseases: such as cancer, etc.;

• Patients with active infection or other diseases which will be aggravated with treatment of glucocorticoid and immunosuppressive therapy;
• Patients positive for HBsAg or hepatitis C antibody;
• Women during pregnancy or lactation, or cannot guarantee effective contraception;
• Patients who did not cooperate with treatment for mental illness or other reasons;
• Patients who had allergic constitution or were allergic to many drugs;
• Patients who were allergic or intolerant to CsA, CYC, or glucocorticoid.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhanguo Li

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhanguo Li, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

Peking University People's Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yue Yang, MD

Role: CONTACT

+86-10-88325230

Facility Contacts

Yue Yang, MD

Role: primary

yyang216@icloud.com

+86-10-88325230

Other Identifiers

U1111-1167-1974

Identifier Type: OTHER

Identifier Source: secondary_id

ChiCTR-IPR-15005990

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-M03

Identifier Type: -

Identifier Source: org_study_id