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

A Phase 2 Proof-of-Concept, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) In Subjects with Systemic Sclerosis with Interstitial Lung Disease

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-023047-15-DE

Enrollment

Registered

2011-12-08

Start date

2012-03-15

Completion date

Unknown

Last updated

2017-04-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

systemic sclerosis associated with interstitial lung disease MedDRA version: 16.1 Level: LLT Classification code 10025109 Term: Lung involvement in systemic sclerosis System Organ Class: 100000004855

Interventions

Trade Name: Imnovid 1 mg hard capsules Pharmaceutical Form: Capsule, hard INN or Proposed INN: Pomalidomide CAS Number: 19171-19-8 Current Sponsor code: CC-4047 Concentration unit: mg milligram(s) Co

Eligibility

Sex/Gender

All

Inclusion criteria

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 20% 8.Repeat FVC at Baseline within 5% of the FVC measured at Screening 9.DLco = 35% and <or= 80% of predicted value at Screening (Documented DLco assessment within 6 months of Screening is acceptable. Test must be repeated prior to randomization if results are not available). 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 <or=14,000/microL (<or= 14 x 109/L) -Absolute neutrophil count (ANC) = 2 x 109/L -Platelet count = 150,000 /microL (= 150 X 109/L) -MDRD eGFR = 60 mL/min -Total bilirubin <or= 2.0 mg/dL -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

Exclusion criteria: 1.Oxygen saturation440msec 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 rate110beats/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 [(<or=100 mg/day). In the event of hospitalization, a subject may use anti-coagulant or anti-thrombotic medications instead of low-dose aspirin, if it is felt to be in the best medical interest of the subject. Aspirin therapy should be reinstituted as soon as the 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

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the safety and tolerability of pomalidomide QD compared to placebo in subjects with SSc-ILD To evaluate the long-term safety and tolerability of pomalidomide (CC- 4047) QD in subjects with SSc-ILD To evaluate the change from Baseline (Week 0) in the FVC in SSc-ILD subjects treated with pomalidomide QD compared to placebo To evaluate the change from Baseline (Week 0) in the mRSS in SSc-ILD subjects treated with pomalidomide QD compared to placebo To evaluate changes from Baseline (Week 0) in GI symptomatology as measured by the UCLA SCTC GIT 2.0 total score in SSc-ILD subjects treated with pomalidomide QD compared to placebo ;Secondary Objective: To characterize the PK of pomalidomide in subjects with SSc-ILD To evaluate the long-term clinical efficacy of PO pomalidomide (CC- 4047) QD in subjects with SSc-ILD To evaluate the clinical efficacy of pomalidomide QD compared to placebo on dyspnea and oxygen saturation ;Primary end point(s): Treatment phase: Safety (type, frequency, severity and relationship of AEs to pomalidomide, laboratory, ECG, physical exam or other changes) and tolerability to pomalidomide Change from Baseline (Week 0) of the FVC at Week 52 Change from Baseline (Week 0) of the mRSS score at Week 52 Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score at Week 52 Open-label Extension Phase: Safety (type, frequency, severity and relationship of AEs and SAEs to pomalidomide, laboratory, ECG, physical exam or other changes) and tolerability to pomalidomide;Timepoint(s) of evaluation of this end point: Treatment phase: Safety: - complete physical exam: screening, week 24, week 52, week 56 - Laboratory: week 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56- ECG: screening, baseline, week 4, 6, 8, 12, 20, 28, 36, 44, 52 and 56 - adverse events: everyweek from week 1 to 56 - survival: every 6 months during the long-term follow-up phase, up to 5 years from treatment initiation. FVC: week 52	—

Measure

Time frame

Main Objective: To evaluate the safety and tolerability of pomalidomide QD compared to placebo in subjects with SSc-ILD To evaluate the long-term safety and tolerability of pomalidomide (CC- 4047) QD in subjects with SSc-ILD To evaluate the change from Baseline (Week 0) in the FVC in SSc-ILD subjects treated with pomalidomide QD compared to placebo To evaluate the change from Baseline (Week 0) in the mRSS in SSc-ILD subjects treated with pomalidomide QD compared to placebo To evaluate changes from Baseline (Week 0) in GI symptomatology as measured by the UCLA SCTC GIT 2.0 total score in SSc-ILD subjects treated with pomalidomide QD compared to placebo ;Secondary Objective: To characterize the PK of pomalidomide in subjects with SSc-ILD To evaluate the long-term clinical efficacy of PO pomalidomide (CC- 4047) QD in subjects with SSc-ILD To evaluate the clinical efficacy of pomalidomide QD compared to placebo on dyspnea and oxygen saturation ;Primary end point(s): Treatment phase: Safety (type, frequency, severity and relationship of AEs to pomalidomide, laboratory, ECG, physical exam or other changes) and tolerability to pomalidomide Change from Baseline (Week 0) of the FVC at Week 52 Change from Baseline (Week 0) of the mRSS score at Week 52 Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score at Week 52 Open-label Extension Phase: Safety (type, frequency, severity and relationship of AEs and SAEs to pomalidomide, laboratory, ECG, physical exam or other changes) and tolerability to pomalidomide;Timepoint(s) of evaluation of this end point: Treatment phase: Safety: - complete physical exam: screening, week 24, week 52, week 56 - Laboratory: week 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 56- ECG: screening, baseline, week 4, 6, 8, 12, 20, 28, 36, 44, 52 and 56 - adverse events: everyweek from week 1 to 56 - survival: every 6 months during the long-term follow-up phase, up to 5 years from treatment initiation. FVC: week 52

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Secondary

Measure	Time frame
Secondary end point(s): Treatment phase: Estimation of pomalidomide PK parameters in plasma, eg, AUCt, Cmax, and tmax (Sparse PK mandatory, Intensive PK only for patients who consent) Change from Baseline (Week 0) of the FVC at Weeks 12, 24, 36 and 48 Change from Baseline (Week 0) of the mRSS at Weeks 12 and 24 Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score at Weeks 12, and 24 Change from Baseline (Week 0) UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Wellbeing and Constipation) at Weeks 12, 24 and 52 Change from Baseline (Week 0) of the oxygen saturation (as measured by pulse oximetry) at Weeks 12, 24 and 52 Change from Baseline (Week 0) dyspnea (as measured by the Transition Dyspnea Index) at Weeks 12, 24 and 52 Open-label Extension Phase -Change from Baseline (Week 0) and Week 52 of the FVC at Weeks 64, 76, 88, 100, 104, 128 and 156 - Change from Baseline (Week 0) and Week 52 of the mRSS at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 of the UCLA SCTC GIT 2.0 total score at Weeks 64, 76, 104, 128 and 156 - Change from Baseline (Week 0) and Week 52 of the UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Well-being and Constipation) at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 of the oxygen saturation (as measured by pulse oximetry) at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 dyspnea (as measured by the Transition Dyspnea Index) at Weeks 64, 76, 104, 128 and 156;Timepoint(s) of evaluation of this end point: Sparse PK assessments: weeks 1 to 4, weeks 6 and 8 Intensive PK assessments: Baseline and week 6 FVC: Weeks 12, 24, 36 and 48 mRSS: weeks 12 and 24 UCLA SCTC GIT: weeks 12, 24, 52 Oxygen saturation: weeks 12, 24 and 52 Transition Dyspnea: weeks 12, 24, 52 Open-label	—

Measure

Time frame

Secondary end point(s): Treatment phase: Estimation of pomalidomide PK parameters in plasma, eg, AUCt, Cmax, and tmax (Sparse PK mandatory, Intensive PK only for patients who consent) Change from Baseline (Week 0) of the FVC at Weeks 12, 24, 36 and 48 Change from Baseline (Week 0) of the mRSS at Weeks 12 and 24 Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score at Weeks 12, and 24 Change from Baseline (Week 0) UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Wellbeing and Constipation) at Weeks 12, 24 and 52 Change from Baseline (Week 0) of the oxygen saturation (as measured by pulse oximetry) at Weeks 12, 24 and 52 Change from Baseline (Week 0) dyspnea (as measured by the Transition Dyspnea Index) at Weeks 12, 24 and 52 Open-label Extension Phase -Change from Baseline (Week 0) and Week 52 of the FVC at Weeks 64, 76, 88, 100, 104, 128 and 156 - Change from Baseline (Week 0) and Week 52 of the mRSS at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 of the UCLA SCTC GIT 2.0 total score at Weeks 64, 76, 104, 128 and 156 - Change from Baseline (Week 0) and Week 52 of the UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Well-being and Constipation) at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 of the oxygen saturation (as measured by pulse oximetry) at Weeks 64, 76, 104, 128 and 156 -Change from Baseline (Week 0) and Week 52 dyspnea (as measured by the Transition Dyspnea Index) at Weeks 64, 76, 104, 128 and 156;Timepoint(s) of evaluation of this end point: Sparse PK assessments: weeks 1 to 4, weeks 6 and 8 Intensive PK assessments: Baseline and week 6 FVC: Weeks 12, 24, 36 and 48 mRSS: weeks 12 and 24 UCLA SCTC GIT: weeks 12, 24, 52 Oxygen saturation: weeks 12, 24 and 52 Transition Dyspnea: weeks 12, 24, 52 Open-label

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Countries

Australia, France, Germany, Italy, Poland, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

Public ContactClinicalTrialDisclosure

Celgene Corporation

ClinicalTrialDisclosure@celgene.com+1888260-1599

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026