A study to see if pomalidomide is safe and works to treat patients with sclerosis affecting the skin on the whole body and that also have lung disease

Phase 1

• Conditions: systemic sclerosis associated with interstitial lung disease; MedDRA version: 16.1Level: LLTClassification code 10025109Term: Lung involvement in systemic sclerosisSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2010-023047-15-DE
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-08
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1.Male or female subjects between 18 and 80 (inclusive) at the time of signing the ICD
2.Body weight =80pounds (36.3kg) at Screening and Baseline
3.Understand and voluntarily sign ICDs prior to the initiation of any study-related assessments/procedures
4.Able to adhere to the study visit schedule and other protocol requirements
5.Diagnosis of SSc as defined by ACR criteria. Subjects will be further classified into lSSc and dSSc based on the criteria presented in Appendix A.
6.Onset of the first non-Raynaud's manifestation of SSc within 7 years of Screening
7. Subjects are required to meet at least one of the following 2 pulmonary-related criteria to be eligible for the study:
-FVC readings = 45% and < 70% at Screening and Baseline (Visit 2) [with or without a documented pre-specified FVC decline or fibrosis
score] OR
-FVC readings = 70% and = 80% at Screening and Baseline (Visit 2) with a documented history of either or both of:
a) A = 5% decrease (expressed as percent predicted or in liters) in FVC in the 24-month period prior to Baseline (Visit 2) based on 3 or more
assessments. Two assessments may be done during the Screening phase provided the assessments are completed at least 2 weeks apart.
b) An HRCT fibrosis score > 20%
8.Repeat FVC at Baseline within 5% of the FVC measured at Screening
9.DLco = 35% and 10.Abnormalities on HRCT consistent with parenchymal changes encountered in SSc: honeycombing or reticular changes with or without ground glass. These changes are usually symmetrical and are often in subpleural and basal locations. Some involvement of both lungs is required.
11.Must meet the following laboratory criteria:
-Hemoglobin =10.0 g/dL
-White blood cell (WBC) count = 3000 /microL (= 3.0 x 109/L) and -Absolute neutrophil count (ANC) = 2 x 109/L
-Platelet count = 150,000 /microL (= 150 X 109/L)
-MDRD eGFR = 60 mL/min
-Total bilirubin -Albumin = 3.0 g/dL
-Aspartate transaminase and alanine transaminase = 1.5 X ILN
-Negative hepatitis B surface antigen is required. Subjects may have a positive anti-hepatitis B core antibody if the anti-hepatitis B surface antibody is positive as well
12.Females of childbearing potential must undergo pregnancy testing based on the frequency outlined in Appendix H and pregnancy results must be negative.
13.Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in Appendix H.
-Abstinence is only acceptable in cases where this is the preferred and usual lifestyle of the subject. Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable.
14.Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in Appendix H.
15.Males must agree not to donate semen or sperm for the duration specified in Appendix H.
16.All subjects must:
-Understand that the IP could have a potential teratogenic risk.
-Agree to abstain from donating blood while taking IP and following discontinuation of investigational product
-Agree not to share IP with another person.
-Other than the sub

Exclusion Criteria

1.Oxygen saturation<92%(room air [sea level] at rest) at Screening or Baseline
2.Known diagnosis of obstructive lung disease as defined by FEV1/FVC ratio <0.7
3.Diagnosis of pulmonary arterial hypertension (PAH) requiring treatment
4.Known diagnosis of other significant respiratory disorders
5.Any significant medical condition, laboratory abnormality or psychiatric illness that would prevent the subject from participating in the study
6. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
7.Any condition that confounds the ability to interpret data from the study
8.Pregnant or lactating females
9.Current clinical diagnosis of another inflammatory connective tissue disease (eg, systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, etc.) Subjects having Sjogren's syndrome secondary to SSc are eligible.
10.History of a thromboembolic event
11.Family history of genetic disease associated with deep vein thrombosis or
thromboembolism
12. History of clinically significant endocrinologic, pulmonary (other than SSc-related), GI (other than SSc-related), neurologic, psychiatric, hepatic, renal, hematologic, cardiovascular, immunologic or other major uncontrolled disease
13.History or current diagnosis of peripheral neuropathy
14.History of alcohol or drug abuse
15.History of any of the following cardiac conditions within 6 months of Screening: acute myocardial infarction, acute coronary syndrome, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery, interventional cardiac catheterization (with or without a stent placement), interventional electrophysiology procedure, presence of implanted permanent pacemaker or presence of implanted defibrillator
16.History of additional risk factors for torsade de pointes
17.Corrected QTcF>440msec on 2 of 3 Screening or Baseline ECGs (predose)
18. Presence of any of the following on 2 of the 3 Screening or Baseline ECGs (pre-dose) at rest: heart rate<50beats/min or >110beats/min, PR interval>220ms, QRS duration>110ms
19.Clinically significant abnormality on any 2 of 3 Screening or Baseline ECGs
20.History of tuberculosis
21.History of HIV infection
22.History of congenital and acquired immunodeficiencies
23.Hepatitis B surface antigen positive. A positive anti-HBc without a positive anti-HBs at Screening
24.Antibodies to hepatitis C at Screening
25.History of malignancy
Prior treatments
26.Use of concomitant medication(s) which could increase the risk for developing deep vein thrombosis
27.Use of melphalan within 52 weeks of Screening
28.The addition of concomitant medications associated with QT prolongation during the course of the study
29.Use of any anti-coagulant or anti-thrombotic medications (other than low dose-aspirin [(Investigator feels it is medically appropriate.
30.Use of any cytotoxic/immunosuppressive agent (other than prednisone = 10 mg/day [mean dose] or equivalent), including but not limited to azathioprine, cyclophosphamide, methotrexate

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified