A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03161483
• Collaborator: (none)
• Enrollment: 289
• Locations: 116
• Arms: 4
• Actual Duration (Months): 48.9
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of an oral treatment regimen of CC-220 versus placebo in adult subjects with active systemic lupus erythematosus.

Approximately 280 subjects with a documented diagnosis of SLE will be randomized 2:2:1:2 to receive CC-220 (0.45 mg QD, 0.3 mg QD or 0.15 mg QD) or identically appearing placebo.

Condition or Disease	Intervention/Treatment	Phase
Lupus Erythematosus, Systemic	Drug: CC-220; Other: Placebo	Phase 2

Detailed Description

The study consists of four phases:

• 4-week Screening Phase

• 24-week placebo-controlled phase Subjects will receive either 0.45 mg QD, 0.3 mg QD, 0.15 mg QD or placebo for the first 24 weeks of treatment.

• 28-week active treatment phase At Week 24, all subjects on placebo will be re-randomized to active treatment.

• 52-week long-term extension phase Subjects who complete the treatment phase may be eligible to roll over into a Long-term Extension of up to 52 weeks of treatment.

• 4 - 12-week observational follow-up All subjects who complete 52 weeks of treatment or discontinue the study early will enter a post-treatment observation follow-up phase. The Observational Follow-up Phase will consist of one visit 4 weeks following cessation of study drug for all subjects with an additional 12-week Observational Follow-up visit for males only.

Study Design

• Study Type: Interventional
• Actual Enrollment: 289 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A PHASE 2, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CC-220 IN SUBJECTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS
• Actual Study Start Date: Jul 6, 2017
• Actual Primary Completion Date: Jan 21, 2020
• Actual Study Completion Date: Aug 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-220 0.45 mg QD Placebo Controlled Phase At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD) Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.	Drug: CC-220; CC-220; Other: Placebo; Placebo QD PO
Experimental: C-220 0.3 mg QD Placebo Controlled Phase At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD) Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.	Drug: CC-220; CC-220; Other: Placebo; Placebo QD PO
Experimental: CC-220 0.15 mg QD Placebo Controlled Phase At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD) Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.	Drug: CC-220; CC-220; Other: Placebo; Placebo QD PO
Placebo Comparator: Placebo Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)	Other: Placebo; Placebo QD PO

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response [Week 24]

   The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day [QD], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and No worsening from Baseline defined by an increase of < 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3

Secondary Outcome Measures

1. Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline [Week 24]

   The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful.

2. Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10 [Week 24]

   The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together.

3. Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index [Week 24]

   The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.

4. Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline [Week 24]

   The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.

5. Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline [Week 24]

   Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.

6. Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline [Week 24]

   Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.

7. Mean Change From Baseline in PGA Score [Week 24]

   The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.

8. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score [Week 24]

   The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total FACIT-Fatigue score ranges from 0 to 52. Note: Data presented is Adjusted mean data.

9. Percentage of Participants With Corticosteroid Reduction [Week 24]

   The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to < 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24

10. Percent Change From Baseline in Corticosteroid Reduction [Week 24]

    Percent change from Baseline in oral corticosteroid (OCS) dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline Note: Data presented is Adjusted mean data.

11. The Total Corticosteroid Dose From Baseline Through Week 24 [Through Week 24]

    Standardized total oral corticosteroid (OCS) dose.

12. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total]

    Number of participants who experienced a TEAE during the course of the study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female 18 years of age or older at the time of signing the informed consent.

• Have a diagnosis of SLE for at least 6 months prior to the Screening Visit and fulfill the 1997 update of the 1982 American College of Rheumatology (ACR) Classification Criteria for SLE at the Screening Visit.

• A SLEDAI 2K score of ≥ 6 points, WITH at least 4 points being a "clinical" SLEDAI 2K score. The "clinical" score excludes points attributable to any urine or blood laboratory results including immunologic measures.

• At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points.

• Have at least one of the following positive antibodies associated with SLE per the central laboratory within the Screening Phase:

• Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:40 or greater, associated with a diagnosis of SLE,

• Anti-dsDNA antibodies elevated to above normal

• Anti-Smith (anti-Sm) antibody elevated to above normal

• Females of childbearing potential must: Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.

o Either commit to true abstinence from heterosexual contact or agree to use two forms of reliable contraception simultaneously.

• Male subjects must: Practice true abstinence or agree to use a barrier contraception during sexual contact.

All subjects must:

• Understand that the IP could have potential teratogenic risk.

• Agree to abstain from donating blood while taking IP and for 28 days following discontinuation of the IP.

• Have been treated with at least one of the following SLE medications prior to the Screening Visit: antimalarials, immunosuppressants, and/or corticosteroids.

• Currently receiving stable doses of at least one of the following medications: systemic corticosteroids, antimalarials, and/or immunosuppressants.

Exclusion Criteria:

• Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.

• Received any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit.

• Have severe lupus nephritis defined as: estimated glomerular filtration rate of < 45 mL/1.73 m2 or proteinuria > 2000 mg/day based on protein to creatinine ratio, or active lupus nephritis that may require 'induction' therapy

• Have active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.

• Have serologic tests consistent with infection with either hepatitis B or hepatitis C, and/or confirmed history of hepatitis B or hepatitis C infection.

• Have history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus, etc).

• Have active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, or any major episode of infection requiring hospitalization or treatment with intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time during the Screening Phase, up through the first dose of IP.

• Have active tuberculosis or a history of latent or active tuberculosis

• Have malignancy or history of malignancy, except for:

• treated (eg, cured) basal cell or squamous cell in situ skin carcinomas

• treated (eg, cured) cervical intraepithelial neoplasia Grade 1 and Grade 2

• treated (eg, cured) carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the Screening Visit.

• Have a diagnosis or history consistent with Antiphospholipid Syndrome or "triple antiphospholipid positivity" (ie, positive lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein).

• Have history of arterial or venous thrombosis

• Have history or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade

• Have presence of active uveitis or any other ophthalmological finding that in the opinion of the Investigator is clinically significant.

• Have other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the primary disease.

• Have clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE

• Does not meet required laboratory criteria.

• Does not meet pre-specified periods for prohibited medications.

• Pregnant or a breast-feeding female.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical and Translational Research Center of Alabama, PC	Tuscaloosa	Alabama	United States	35406
2	AZ Arthritis and Rheum Rsch, PLLC	Mesa	Arizona	United States	85202
3	Saint Jude Heritage Medical Center	Fullerton	California	United States	92835
4	University of California San Diego Medical Center	La Jolla	California	United States	92037
5	UCLA Division of Rheumatology	Los Angeles	California	United States	90095
6	Desert Medical Advances	Palm Desert	California	United States	92260
7	C Michael Neuwelt M D	San Leandro	California	United States	94578
8	Inland Rheumatology Clinical Trials	Upland	California	United States	91786
9	University of Colorado Denver	Aurora	Colorado	United States	80045
10	Yale University School of Medicine	New Haven	Connecticut	United States	06520
11	Centre For Rheumatology, Immun. And Arthritis	Fort Lauderdale	Florida	United States	33334
12	University of Florida College of Medicine	Gainesville	Florida	United States	32610
13	University of Miami	Miami	Florida	United States	33136
14	Integral Rheumatology and Immunology Specialists	Plantation	Florida	United States	33324
15	Bay Care Medical Group	Tampa	Florida	United States	33614
16	Emory University School of Medicine	Atlanta	Georgia	United States	30303
17	Piedmont Hospital - Atlanta	Atlanta	Georgia	United States	30309
18	Jefrey Lieberman, MD, PC	Decatur	Georgia	United States	30033-5910
19	North Georgia Rheumatology	Lawrenceville	Georgia	United States	30046
20	Clinic of Robert Hozman	Skokie	Illinois	United States	60076
21	University of Maryland - School of Medicine	Baltimore	Maryland	United States	21201
22	Beth Israel Deaconness Medical Center	Boston	Massachusetts	United States	02215
23	Advanced Rheumatology	Lansing	Michigan	United States	48910
24	Great Lakes Center of Rheumatology	Lansing	Michigan	United States	48910
25	Arthritis and Osteoporosis Associates of New Mexico	Las Cruces	New Mexico	United States	88011-4741
26	Montefiore Medical Center	Bronx	New York	United States	10461
27	North Shore-LIJ Health System-Division of Rheumatology	Great Neck	New York	United States	11021
28	NYU Langone Medical Center	New York	New York	United States	10016
29	SUNY Upstate Medical University	Syracuse	New York	United States	13210
30	DJL Clinical Research	Charlotte	North Carolina	United States	28210
31	Shanahan Rheumatology and Immunotherapy	Raleigh	North Carolina	United States	27617
32	MetroHealth Medical Systems	Cleveland	Ohio	United States	44109
33	St. Anthony's Medical Center	Oklahoma City	Oklahoma	United States	73102
34	Hershey Medical Center	Hershey	Pennsylvania	United States	17033-8807
35	University of Pennsylvania Department of Dermatology	Philadelphia	Pennsylvania	United States	19104
36	University of Pittsburgh UPMC Lupus Center of Excellence	Pittsburgh	Pennsylvania	United States	15213
37	Advanced Rheumatology & Arthritis Research Center, PC	Wexford	Pennsylvania	United States	15090
38	Medical University of South Carolina	Charleston	South Carolina	United States	29425
39	UT Southwestern Medical Center	Dallas	Texas	United States	75390
40	Pioneer Research Solutions	Houston	Texas	United States	77099
41	Virginia Mason Medical Center	Seattle	Washington	United States	98101
42	Organización Médica de Investigación	Buenos Aires		Argentina	C1015ABO
43	Hospital General de Agudos Dr. Jose Maria Ramos Mejia	Buenos Aires		Argentina	C1221ADC
44	Hospital Britanico de Buenos Aires	Buenos Aires		Argentina	C1280AEB
45	Consultora Integral de Salud Centro Médico Privado	Cordoba		Argentina	5000
46	Hospital Privado Centro Medico de Cordoba	Cordoba		Argentina	X5016
47	CER Instituto Mèdico	Quilmes		Argentina	B1878DVB
48	Instituto de Investigaciones Clinicas de Quilmes	Quilmes		Argentina	B1878GEG
49	Centro Medico Privado de Reumatologia	San Miguel de Tucumán		Argentina	T4000AXL
50	Hopital Erasme	Brussels		Belgium	1070
51	Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg	Leuven		Belgium	3000
52	CHU de Liege	Liège		Belgium	4000
53	Centro Internacional de Pesquisas	Goiânia	Goiás	Brazil	74110-120
54	Centro de Estudos em Terapias Inovadoras LTDA	Curitiba	Paraná	Brazil	80030
55	LMK Servicos Medicos S/S	Porto Alegre	Rio Grande Do Sul	Brazil	90480
56	State University of Campinas UNICAMP	Campinas	São Paulo	Brazil	13083-888
57	Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte		Brazil	30150-221
58	Hospital de Clinicas de Porto Alegre	Porto Alegre, RS		Brazil	90035-003
59	Centro de Imunoterapia de Ipanema (CITIPA)	Rio de Janeiro		Brazil	22411-001
60	The University of Calgary	Calgary	Alberta	Canada	T2N 4Z6
61	University of Manitoba	Winnipeg	Manitoba	Canada	R3Y1X7
62	MAC Research Incorporated	Hamilton	Ontario	Canada	L8N 2B6
63	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
64	CHUL du CHU de Quebec	Quebec		Canada	G1V 4G2
65	Clinique de Rhumatologie Du Centre Du Quebec	Quebec		Canada	G8Z 1Y2
66	IPS Centro Integral de Reumatologia del Caribe Circaribe S.A.S.	Barranquilla		Colombia	080002
67	Centro de Investigacion en Reumatologia y Especialidades Medicas S.A.S. - Cireem S.A.S	Bogota		Colombia	110221
68	Idearg S.A.S.	Bogota		Colombia	111211
69	Medicity S.A.S.	Bucaramanga		Colombia	680003
70	Servimed S.A.S.	Bucaramanga		Colombia	680003
71	Preventive Care	Chia		Colombia	250001
72	Reumalab - Centro Integral de Reumatologia	Medellin		Colombia	050010
73	Hospital Pablo Tobon Uribe	Medellin		Colombia	050034
74	CHRU de Lille France	Lille Cedex		France	59037
75	Assistance Publique - Hopitaux de Paris - Hopital Universitaire Pitie Salpetriere	Paris		France	75651
76	CHU Hautepierre	Strasbourg		France	67098
77	Universitatsklinikum Schleswig-Holstein	Kiel		Germany	24105
78	Universitaetsklinikum Koeln	Koeln		Germany	50937
79	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz		Germany	55131
80	Qualiclinic kft	Budapest		Hungary	1036
81	Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet	Budapest		Hungary	1097
82	Bekes Megyei Kozponti Korhaz	Gyula		Hungary	5700
83	ASST Spedali Civili P.O. di Brescia	Brescia		Italy	25123
84	University of Ferrara, Azienda Ospedaliera-Universitaria S.Anna	Ferrara		Italy	44124
85	Azienda Ospedaliero - Universitaria di Cagliari	Monserrato		Italy	09042
86	Centro de Investigacion en Artritis y Osteoporosis	Mexicali	Baja California	Mexico	21200
87	Biológicos Especializados S.A. de C.V.	Mexico	Distrito Federal	Mexico	06700
88	Clinica Integral de Osteoporosis y Artitis Reumatoide CLINOSAR	Mexico	Distrito Federal	Mexico	06760
89	Centro de Investigación y Tratamiento Reumatológico	Mexico	Distrito Federal	Mexico	44690
90	Centro Integral en Reumatología, S.A. de C.V.	Guadalajara	Jalisco	Mexico	44160
91	Centro de Alta Especialidad en Reumatología e Investigación del Potosí S.C.	San Luis Potosi	San Luis Potosí	Mexico	78213
92	Unidad de Atencion Medica e Investigacion en Salud, S.C.	Merida	Yucatán	Mexico	97130
93	Hospital Angeles Lindavista	D.f, Df		Mexico	07760
94	Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
95	Samodzielny Publiczny Zespól Opieki Zdrowotnej w Koscianie Szpital im. Teodora Dunina	Koscian		Poland	64-000
96	Centrum Medyczne Plejady	Krakow		Poland	30-349
97	Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Reumatologii i Ukladowych Chorob Tkanki Laczne	Lublin		Poland	20-954
98	Niepubliczny Zaklad Opieki Zdrowotnej Biogenes Sp. z o.o.	Wroclaw		Poland	53-224
99	City Clinical Hospital	Kazan		Russian Federation	420103
100	Kemerovo State Medical Academy	Kemerovo		Russian Federation	650066
101	Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru	Moscow		Russian Federation	115522
102	Orenburg State Medical Academy	Orenburg		Russian Federation	460000
103	Saint Petersburg Research Institute for Emergency Medical Care	St. Petersburg		Russian Federation	192242
104	Leningrad Regional Clinical Hospital	St. Petersburg		Russian Federation	194291
105	State Higher Educational Institution	St. Petersburg		Russian Federation	195067
106	BioMed, LLC.	Vladimir		Russian Federation	600005
107	Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy	Voronezh		Russian Federation	394066
108	Institute of Rheumatology Belgrade	Belgrade		Serbia	11000
109	Military Medical Academy	Belgrade		Serbia	11000
110	Clinical Center Kragujevac	Kragujevac		Serbia	34000
111	Institute Niska Banja	Niska Banja		Serbia	18205
112	Hospital Universitario a Coruna	A Coruña		Spain	15006
113	Hospital Universitario Vall D hebron	Barcelona		Spain	28040
114	Hospital Universitario de Canarias	La Laguna		Spain	38320
115	Hospital Marques de Valdecilla	Santander		Spain	39008
116	Hospital Universitario Araba - Txagorritxu	Vitoria-Gasteiz		Spain	01009

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Nataliya Agafonova, MD, Celgene Corporation

Study Documents (Full-Text)

• Study Protocol - Aug 15, 2018
• Statistical Analysis Plan - Jun 20, 2019

More Information

Publications

• Nakayama Y, Kosek J, Capone L, Hur EM, Schafer PH, Ringheim GE. Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity. J Immunol. 2017 Oct 1;199(7):2388-2407. doi: 10.4049/jimmunol.1601725. Epub 2017 Aug 28.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT03161483
• Other Study ID Numbers: CC-220-SLE-002; U1111-1195-7804
• First Posted: May 19, 2017
• Last Update Posted: Sep 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celgene: CC-220; Safety; Efficacy; Active Systemic Lupus Erythematosus
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

Participant Flow

Pre-assignment Detail	Placebo-controlled phase: 289 participants were randomized and 288 treated

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Period Title: Overall Study
STARTED	83	42	82	81
COMPLETED	73	39	62	73
NOT COMPLETED	10	3	20	8

Baseline Characteristics

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD	Total
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day	Total of all reporting groups
Overall Participants	83	42	82	81	288
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.4 (13.3)	43.8 (13.0)	44.7 (13.7)	46.4 (11.2)	44.7 (12.8)
Age, Customized (Count of Participants)
< 40 years old	33 39.8%	15 35.7%	31 37.8%	24 29.6%	103 35.8%
>= 40 to <= 50	26 31.3%	15 35.7%	21 25.6%	28 34.6%	90 31.3%
> 50 to < 65	19 22.9%	10 23.8%	24 29.3%	24 29.6%	77 26.7%
>= 65	5 6%	2 4.8%	6 7.3%	5 6.2%	18 6.3%
Sex: Female, Male (Count of Participants)
Female	81 97.6%	41 97.6%	77 93.9%	79 97.5%	278 96.5%
Male	2 2.4%	1 2.4%	5 6.1%	2 2.5%	10 3.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	41 49.4%	21 50%	46 56.1%	33 40.7%	141 49%
Not Hispanic or Latino	42 50.6%	21 50%	36 43.9%	48 59.3%	147 51%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	2 2.4%	5 11.9%	1 1.2%	5 6.2%	13 4.5%
Asian	0 0%	0 0%	1 1.2%	0 0%	1 0.3%
Black or African American	7 8.4%	3 7.1%	6 7.3%	5 6.2%	21 7.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
White	60 72.3%	29 69%	59 72%	60 74.1%	208 72.2%
Not collected or reported	0 0%	0 0%	0 0%	0 0%	0 0%
Other	14 16.9%	5 11.9%	15 18.3%	11 13.6%	45 15.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response
Description	The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day [QD], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and No worsening from Baseline defined by an increase of < 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Primary analysis based on Intent-to-treat (ITT) Population (all randomized participants who received at least one dose of investigational product) and nonresponder imputation (NRI). Participants with insufficient data for response determination at the given time point are considered nonresponders.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Number [Number of participants]	29 34.9%	20 47.6%	33 40.2%	44 54.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.214
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; -6.57 to 29.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.512
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; -9.77 to 19.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	19.4
	Confidence Interval	(2-Sided) 95%; 4.12 to 33.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline
Description	The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Participants with insufficient data for response determination at the given time point are considered nonresponders.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Number [Number of participants]	30 36.1%	20 47.6%	35 42.7%	45 55.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.264
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	10.3
	Confidence Interval	(2-Sided) 95%; -7.66 to 27.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.399
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	6.5
	Confidence Interval	(2-Sided) 95%; -8.45 to 21.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95%; 4.01 to 33.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10
Description	The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population with Baseline CLASI activity score ≥ 10

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	16	11	18	19
Number [Number of participants]	8 9.6%	8 19%	8 9.8%	13 16%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.446
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	24.0
	Confidence Interval	(2-Sided) 95%; -12.38 to 53.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -27.64 to 39.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.488
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	14.2
	Confidence Interval	(2-Sided) 95%; -19.54 to 44.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index
Description	The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Number [Number of participants]	65 78.3%	38 90.5%	59 72%	70 86.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	12.4
	Confidence Interval	(2-Sided) 95%; -2.74 to 24.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -18.43 to 8.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.182
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	8.0
	Confidence Interval	(2-Sided) 95%; -3.88 to 19.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline
Description	The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Number [Percentage of participants]	78.3 94.3%	90.5 215.5%	73.2 89.3%	85.2 105.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	12.1
	Confidence Interval	(2-Sided) 95%; -2.98 to 23.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.521
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	-4.3
	Confidence Interval	(2-Sided) 95%; -17.36 to 8.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.267
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; -5.24 to 18.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline
Description	Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population; Subjects with >=2 Swollen Joints, with a baseline value and a value at the time point.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	62	33	54	56
Mean (95% Confidence Interval) [swollen joints]	-6.7	-6.0	-6.0	-6.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.116
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.2 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.094
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.881
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline
Description	Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population; Participants with >=2 Tender Joints, with a baseline value and a value at the time point.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	62	33	54	56
Mean (95% Confidence Interval) [tender joints]	-7.9	-6.8	-6.7	-7.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.0 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.621
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline in PGA Score
Description	The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population with a baseline value and a value at the time point.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	66	38	63	70
Mean (Standard Deviation) [scores on a scale]	-0.803 (0.605)	-0.805 (0.528)	-0.819 (0.629)	-0.883 (0.546)

9. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score
Description	The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total FACIT-Fatigue score ranges from 0 to 52. Note: Data presented is Adjusted mean data.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population; participants with a baseline value and a value at the time point

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	67	38	60	69
Mean (95% Confidence Interval) [scores on a scale]	3.8	2.7	3.1	5.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -4.7 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.681
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -3.7 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.350
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted mean
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -1.6 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Corticosteroid Reduction
Description	The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to < 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population; Participants with Baseline OCS Dose >= 10 mg/day Participants with insufficient data for response determination at the given time point are considered nonresponders.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	31	17	30	32
Week 24, <= 7.5 mg/day	3.2 3.9%	0.0 0%	3.3 4%	0.0 0%
Week 24, < 10 mg/day	6.5 7.8%	0.0 0%	3.3 4%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments	<= 7.5 mg/day
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -15.13 to 15.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments	< 10 mg/day
Statistical Test of Hypothesis	p-Value	>0.999
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Stratified difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -17.74 to 13.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Corticosteroid Reduction
Description	Percent change from Baseline in oral corticosteroid (OCS) dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline Note: Data presented is Adjusted mean data.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population; Participants with the Baseline OCS Dose >= 10 mg/day, with a baseline value and a value at the time point.

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	26	17	25	30
Mean (95% Confidence Interval) [percent change from baseline]	-7.9	-5.1	-3.8	-1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.15 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.535
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted means
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -6.0 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.30 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.309
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted means
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; -3.9 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PBO QD, 0.45 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.091
	Comments
	Method	longitudinal data analysis model
	Comments
Method of Estimation	Estimation Parameter	Difference in adjusted means
	Estimated Value	6.5
	Confidence Interval	(2-Sided) 95%; -1.0 to 14.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	The Total Corticosteroid Dose From Baseline Through Week 24
Description	Standardized total oral corticosteroid (OCS) dose.
Time Frame	Through Week 24

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Mean (Standard Deviation) [mg]	1139.7 (916.9)	1101.9 (827.1)	1071.8 (965.0)	1105.5 (969.3)

13. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	Number of participants who experienced a TEAE during the course of the study
Time Frame	from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	PBO QD	0.15 mg QD	0.30 mg QD	0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day	Participants dosed with CC-220 at 0.15 mg once a day	Participants dosed with CC-220 at 0.30 mg once a day	Participants dosed with CC-220 at 0.45 mg once a day
Measure Participants	83	42	82	81
Any TEAE	54 65.1%	31 73.8%	64 78%	63 77.8%
Any Drug-related TEAE	24 28.9%	14 33.3%	36 43.9%	32 39.5%
Any Serious TEAE	7 8.4%	3 7.1%	4 4.9%	6 7.4%
Any Severe TEAE	5 6%	3 7.1%	4 4.9%	1 1.2%
Any TEAE Leading to Drug Interruption	15 18.1%	10 23.8%	14 17.1%	23 28.4%
Any TEAE Leading to Drug Withdrawal	6 7.2%	2 4.8%	11 13.4%	4 4.9%
Any TEAE Leading to Death	1 1.2%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	From first dose to 28 days post-last dose of the placebo-controlled phase (through Week 24), approximately 28 weeks total.
Arm/Group Title	PBO Controlled - PBO		PBO Controlled - 0.15 mg QD		PBO Controlled - 0.30 mg QD		PBO Controlled - 0.45 mg QD
Arm/Group Description	Placebo-matching treatment once a day		Participants dosed with CC-220 at 0.15 mg once a day		Participants dosed with CC-220 at 0.30 mg once a day		Participants dosed with CC-220 at 0.45 mg once a day
All Cause Mortality
	PBO Controlled - PBO		PBO Controlled - 0.15 mg QD		PBO Controlled - 0.30 mg QD		PBO Controlled - 0.45 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Serious Adverse Events
	PBO Controlled - PBO		PBO Controlled - 0.15 mg QD		PBO Controlled - 0.30 mg QD		PBO Controlled - 0.45 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/83 (8.4%)		3/42 (7.1%)		4/82 (4.9%)		6/81 (7.4%)
Cardiac disorders
Cardiac tamponade	0/83 (0%)		1/42 (2.4%)		0/82 (0%)		0/81 (0%)
Pericarditis	0/83 (0%)		1/42 (2.4%)		0/82 (0%)		0/81 (0%)
Gastrointestinal disorders
Diverticular perforation	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
General disorders
Implant site pain	0/83 (0%)		1/42 (2.4%)		0/82 (0%)		0/81 (0%)
Influenza like illness	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Infections and infestations
Escherichia urinary tract infection	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Gastroenteritis viral	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Pneumonia	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Urinary tract infection enterococcal	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Injury, poisoning and procedural complications
Acetabulum fracture	0/83 (0%)		0/42 (0%)		1/82 (1.2%)		0/81 (0%)
Forearm fracture	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Lower limb fracture	0/83 (0%)		1/42 (2.4%)		0/82 (0%)		0/81 (0%)
Radius fracture	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	3/83 (3.6%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Nervous system disorders
Brain stem infarction	0/83 (0%)		0/42 (0%)		1/82 (1.2%)		0/81 (0%)
Encephalopathy	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Hemiparesis	0/83 (0%)		0/42 (0%)		1/82 (1.2%)		0/81 (0%)
Reproductive system and breast disorders
Endometriosis	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Epistaxis	0/83 (0%)		0/42 (0%)		0/82 (0%)		1/81 (1.2%)
Hypoxia	0/83 (0%)		0/42 (0%)		1/82 (1.2%)		0/81 (0%)
Laryngeal oedema	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Pulmonary embolism	1/83 (1.2%)		0/42 (0%)		0/82 (0%)		0/81 (0%)
Vascular disorders
Deep vein thrombosis	1/83 (1.2%)		0/42 (0%)		1/82 (1.2%)		0/81 (0%)
Other (Not Including Serious) Adverse Events
	PBO Controlled - PBO		PBO Controlled - 0.15 mg QD		PBO Controlled - 0.30 mg QD		PBO Controlled - 0.45 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/83 (22.9%)		16/42 (38.1%)		30/82 (36.6%)		34/81 (42%)
Blood and lymphatic system disorders
Leukopenia	1/83 (1.2%)		1/42 (2.4%)		3/82 (3.7%)		5/81 (6.2%)
Neutropenia	2/83 (2.4%)		2/42 (4.8%)		6/82 (7.3%)		9/81 (11.1%)
Gastrointestinal disorders
Diarrhoea	0/83 (0%)		3/42 (7.1%)		2/82 (2.4%)		3/81 (3.7%)
Infections and infestations
Influenza	3/83 (3.6%)		3/42 (7.1%)		4/82 (4.9%)		5/81 (6.2%)
Nasopharyngitis	1/83 (1.2%)		3/42 (7.1%)		1/82 (1.2%)		7/81 (8.6%)
Sinusitis	1/83 (1.2%)		1/42 (2.4%)		0/82 (0%)		5/81 (6.2%)
Upper respiratory tract infection	4/83 (4.8%)		3/42 (7.1%)		7/82 (8.5%)		10/81 (12.3%)
Urinary tract infection	3/83 (3.6%)		2/42 (4.8%)		13/82 (15.9%)		8/81 (9.9%)
Nervous system disorders
Headache	5/83 (6%)		2/42 (4.8%)		0/82 (0%)		0/81 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.