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

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



Sponsors

Lead Sponsor



Source

Celgene

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

Yes

Is Fda Regulated Device

No


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.

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.

- 4-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.

Overall Status

Not yet recruiting

Start Date

2017-06-30

Completion Date

2020-01-20

Primary Completion Date

2019-07-22

Phase

Phase 2

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Proportion of subjects who achieve SRI(4) response- Week 24
Week 24

Secondary Outcome

Measure

Time Frame

Proportion of subjects who achieve SRI(4) response - Week 52
Week 52
Proportion of subjects with SLEDAI 2K score improvement of ≥ 4 points from Baseline
Weeks 24 and 52
Proportion of subjects with a ≥ 50% reduction in Cutaneous Lupus Area and Severity Index (CLASI) activity score from baseline, in subjects with Baseline CLASI activity score ≥ 10
Weeks 24 and 52
Proportion of subjects with no new organ system affected as defined by 1 or more BILAG A or new 2 or more BILAG B items compared to Baseline using BILAG 2004 Index
Weeks 24 and 52
Percentage of subjects with no worsening (increase of <0.30 points from Baseline) in Physician's Global Assessment (PGA) compared to Baseline
Week 24
Mean change from Baseline in swollen joint count in subjects with ≥ 3 swollen joints at Baseline
Week 24 and 52
Mean change from Baseline in tender joint count in subjects with ≥ 3 tender joints at Baseline
Week 24 and 52
Mean change from Baseline in PGA score
Week 24 and 52
Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score
Week 24 and 52
Major clinical response defined as BILAG C or better in all organ domains at Week 24 with maintenance of this response through Week 52
Week 24 and 52
Corticosteroid Reduction- Week 24
Week 24
Corticosteroid Reduction- Week 52
Week 52
Area under the curve (AUC) of SLE flare as defined by the SLE Flare Index
Up to 52 weeks
Percentage of subjects experiencing a SLE flare as defined by the SLE Flare Index
Up to 52 weeks
: Time to flare as defined by the SLE Flare Index
Up to 52 weeks
Change from Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index
52 weeks

Enrollment

280

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

0.45 mg QD PO

Arm Group Label

CC-220 0.45 mg QD Placebo Controlled Phase


Intervention Type

Drug

Intervention Name


Description

0.3 mg QD PO

Arm Group Label

C-220 0.3 mg QD Placebo Controlled Phase


Intervention Type

Drug

Intervention Name


Description

0.15 mg QD PO

Arm Group Label

CC-220 0.15 mg QD Placebo Controlled Phase


Intervention Type

Other

Intervention Name


Description

Placebo QD PO

Arm Group Label

CC-220 0.45 mg QD Placebo Controlled Phase

C-220 0.3 mg QD Placebo Controlled Phase

CC-220 0.15 mg QD Placebo Controlled Phase

Placebo




Eligibility

Criteria

Inclusion Criteria:

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

Able and willing to adhere to the visit schedule and other protocol requirements.

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.

At the Screening Visit a Systemic Lupus Erythematosus Disease Activity Index (2K) (SLEDAI
2K) score of ≥ 6 points, at least four points of which are a "clinical" SLEDAI 2K score.
The "clinical" score is the SLEDAI 2K assessment score without the inclusion of points
attributable to any urine or blood laboratory results including immunologic measures.
Neurologic descriptors of the SLEDAI 2K are not counted towards the SLEDAI study entry
criteria.

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

Positive antibodies associated with SLE, which must include at least one of the following
within the Screening Phase:

- Positive antinuclear antibody (ANA) test at the central laboratory with a titer of
1:80 or greater, associated with a diagnosis of SLE, Anti-dsDNA antibodies elevated
to above normal as per the central laboratory,

- Anti-Smith (anti-Sm) antibody elevated to above normal as per the central laboratory.

Females of childbearing potential (FCBP) must:

- Have two negative pregnancy tests as verified by the investigator prior to starting
study therapy, one within 10 to 14 days prior to the first dose of CC-220 and again
within 24 hours before taking the first dose of CC-220. She must agree to ongoing
pregnancy testing during the course of the study, and after end of study treatment.
This applies even if the subject practices true abstinence from heterosexual contact.

- Either commit to true abstinence2 from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use two forms of reliable
contraception simultaneously. One must be a highly effective method and one
additional effective (barrier) method, and both must be practiced without
interruption, 28 days prior to starting investigational product, during the study
therapy (including dose interruptions), and for 28 days after discontinuation of
study therapy.

- Male subjects must: Practice true abstinence or agree to use a barrier contraception
(male latex condom or non-latex condom NOT made out of natural [animal] membrane [for
example, polyurethane]) during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study, during dose interruptions
and for at least 90 days following investigational product discontinuation, even if
he has undergone a successful vasectomy.

- Male subjects must agree not to donate semen or sperm during therapy and for at least
90 days following the discontinuation of Investigational Product (IP).

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.

- Agree not to share IP with another person.

- Other than the subject, FCBP and males able to father a child should not handle the
IP or touch the capsules unless gloves are worn.

- Be counseled about pregnancy precautions and risks of fetal exposure as described in
the Pregnancy Prevention Plan.

If taking oral corticosteroids, must be on for at least 4 weeks prior to the Screening
Visit, and maintained on a stable dose of ≤ 20 mg/d of prednisone or equivalent for at
least 2 weeks prior to the Baseline Visit.

If taking SLE standard of care treatment (e.g. anti-malarial, mycophenolate mofetil,
azathioprine) for 12 weeks prior to and be on a stable dose for at least 4 weeks prior to
Baseline.

Exclusion Criteria:

Must be off prohibited medications for a pre-specified period of time.

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

Received an investigational product within 5 pharmacokinetic half-lives or one month,
whichever is longer, prior to the Baseline Visit.

Severe lupus nephritis defined as: estimated glomerular filtration rate (eGFR) of < 45
mL/1.73 m2 or proteinuria > 2000 mg/day if stable for the past 3 months or proteinuria >
500 mg/day if unstable.

Proteinuria will be based upon spot urine testing.

Active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening
Visit.

History or confirmed positive test for hepatitis B History of congenital and/or acquired
mmunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus
[HIV], etc).

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.

Active tuberculosis (TB) or a history of incompletely treated TB, or a positive,
QuantiFERON®-TB Gold test.

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 or carcinoma in situ of the
cervix with no evidence of recurrence within 5 years of the Screening Visit.

Diagnosis of Antiphospholipid Syndrome History of arterial or venous thrombosis within one
year of the Screening Visit.

History or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade 2.

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

Other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the
primary disease.

Clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE

Does not meet required laboratory criteria.

Pregnant or a breast-feeding female.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Gender

All

Minimum Age

18 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Marla Hochfeld, MD
Study Director
Celgene Corporation

Overall Contact

Last Name

Associate Director Clinical Trial Disclosure

Phone

1-888-260-1599

Email

[email protected]


Verification Date

2017-05-01

Lastchanged Date

2017-05-18

Firstreceived Date

2017-05-18

Responsible Party

Responsible Party Type

Sponsor


Keywords


Has Expanded Access

No

Condition Browse


Number Of Arms

4

Arm Group

Arm Group Label

CC-220 0.45 mg QD Placebo Controlled Phase

Arm Group Type

Experimental

Description

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)


Arm Group Label

C-220 0.3 mg QD Placebo Controlled Phase

Arm Group Type

Experimental

Description

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)


Arm Group Label

CC-220 0.15 mg QD Placebo Controlled Phase

Arm Group Type

Experimental

Description

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)


Arm Group Label

Placebo

Arm Group Type

Placebo Comparator

Description

Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)



Firstreceived Results Date

N/A

Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Participant, Care Provider, Investigator, Outcomes Assessor



ClinicalTrials.gov processed this data on May 19, 2017

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Interventions

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Study Phase

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In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

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