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

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2010-023047-15-DE
• Date of registration: 08/12/2011
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 15/03/2012
• Target sample size: 88
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023047-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion 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 < 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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

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)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

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

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

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
mRSS: week 52
UCLA SCTC GIT: week 52

Open Label extension: See tables 2 and 3 of protocol for full details
-Targeted Physical exam, YR 1 weeks 54,56,60,64,72,80,88,96,104
-Vital signs, Pregnancy tests, Adverse events, Assessment for
malignancy, Concomitant meds and procedures, Pomalidomide
counseling :
Yr 1 weeks,
52,53,54,55,56,58,60,62,64,68,72,76,80,84,88,92,96,100,104

Secondary Outcome(s)

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 Extension Phase
- FVC at Weeks 64, 76, 88, 100,104, 128 and 156
- mRSS at Weeks 64, 76, 104,128 and 156
-UCLA SCTC GIT 2.0 total score at Weeks 64, 76, 104, 128 and 156
- 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
-oxygen saturation at Weeks 64, 76, 104, 128 and 156
- dyspnea (Transition Dyspnea Index) at Weeks 64, 76, 104, 128 and
156

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

Secondary ID(s)

NCT01559129

CC-4047-SSC-001

Source(s) of Monetary Support

Celgene Corporation