| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| SYSTEMIC LUPUS ERYTHEMATOSUS |
|
| E.1.1.1 | Medical condition in easily understood language |
| Heterogeneous, inflammatory, multisystem autoimmune disease in which antinuclear antibodies occur. "Lupus erythematosus" describes the typical rash of SLE. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025134 |
| E.1.2 | Term | Lupus erythematosus |
| E.1.2 | System Organ Class | 100000004859 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate additional measures of clinical disease activity 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 subjects with active SLE at Week 24
- To assess the reduction in steroid use
- To assess the reduction in fatigue
- To evaluate the safety and tolerability of three dose of CC-220 (0.45 mg QD, 0.3 mg QD, and 0.15 mg QD) compared to placebo in subjects with active SLE
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Male or female 18 years of age or older at the time of signing the
informed consent.
•Understand and voluntarily sign informed consent forms (ICFs) prior to
the initiation of any study specific assessments/procedures.
•Able and willing to adhere to the visit schedule and other protocol requirements.
Disease Specific
•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. As subjects with neurological manifestations of lupus are excluded from the study, no neurologic descriptors of the SLEDAI 2K score (items 1 to 7) will be counted towards the SLEDAI study entry criteria.
•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 with a titer of ≥ 1:40,
associated with a diagnosis of SLE,
* Anti-dsDNA antibodies elevated to above normal,
* Anti-Smith (anti-Sm) antibody elevated to above normal.
* All subjects must receive approval by the adjudication committee
(Section 3.1.3) prior to enrollment into the study.
Pregnancy
All male and female subjects should be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan (provided separately).
•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 CC220.
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 abstinence 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 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.
Concomitant Medications
•Must 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 permitted
medications per the protocol.
•If taking steroids, subjects must be on oral corticosteroids (OCS) 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 hydroxychloroquine, quinacrine, chloroquine, methotrexate,
leflunomide, sulfasalazine, mycophenolate mofetil, mycophenolic acid,
azathioprine, 6-mercaptopurine, tacrolimus or cyclosporine, subjects
must have been treated for 12 weeks prior to and be on a stable dose for
at least 8 weeks prior to Baseline.
•Subjects taking NSAIDs or analgesics on a regular basis must be on a
stable dose 2 weeks prior to the Screening Visit.
For Long-term Extension Phase only:
Subjects have completed participation in the placebo-controlled and
active treatment study phases.
Subjects eligibility to enter the long-term extension phase will be
dependent on the ongoing adjudication review.
|
|
| E.4 | Principal exclusion criteria |
1.The subject has received:
a.Cyclophosphamide within 6 months of the Baseline Visit. Previous use
of Melphalan or other alkylating agents is prohibited.
b.Etanercept within 8 weeks prior to the Baseline Visit.
c.Belimumab within 3 months prior to the Baseline Visit.
d.B-cell depleting or modulating agents, such as rituximab or anti-CD22
therapy, within 1 year prior to the Baseline Visit.
e.Any other biologic or non-biologic immunosuppressive agent within 2
months of 5 pharmacokinetic half-lives (whichever is longer) prior to the
Baseline Visit.
2.The subject has been treated with intra-articular, intralesional,
subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6
weeks prior to the Baseline Visit.
3.The subject has received high potency topical or intralesional
corticosteroids, topical immunosuppressants, and/or retinoids within 2
weeks of the Screening Visit.
4.The subject has undergone plasmapheresis within 3 months of the
Baseline Visit.
5.The subject has received IV immunoglobulin within 3 months of the
Baseline Visit.
6.The subject has received strong inhibitors or inducers of CYP3A4/5,
including grapefruit, St. John's Wort or related products within two
weeks prior to the Baseline Visit.
7.The subject has a planned or received immunization with a live or live
attenuated vaccine within 2 months prior to the Baseline Visit and for 2
months after administration of the last dose of IP.
Disease Severity
8.The subject has an estimated glomerular filtration rate (eGFR) of < 45
mL/min/1.7 m2 or proteinuria > 2000 mg/day based on protein to
creatinine ratio, or has active lupus nephritis that in the opinion of the
adjudication committee may require 'induction' therapy.
9.The subject has active, severe or unstable neuropsychiatric lupus
disease (e.g., poorly controlled seizure disorder, acute confusional state,
myelitis, stroke or stroke syndrome, cerebellar ataxia or dementia
related to SLE, psychosis, organic brain syndrome, cerebrovascular
accident [CVA], cerebritis or CNS vasculitis), within 6 months of the
Screening Visit.
Concomitant Disease
10.The subject has QTcF of > 450 milliseconds on the screening ECG.
11.The subject has serologic tests during Screening consistent with
infection with either hepatitis B or hepatitis C, and/or confirmed history
of hepatitis B or hepatitis C infection. Subjects with isolated positive
hepatitis B surface antibody are not excluded.
12.The subject has a history of congenital and/or acquired
immunodeficiencies.
13.The subject has active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections or has had 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.
14.The subject has a history of latent or active TB, unless there is
medical record documentation of successful completion of a standard
course of treatment per local guidelines.
15.The subject has an abnormal chest radiograph with evidence of active
infection or possible malignancy. Alternatively, PA or PA/lateral
radiographs or CT scans that were taken within the 3 months (or longer
periods based on local health authority requirements) prior to the
Screening Visit will be accepted for evaluation for participation in the
study.
16.The subject has 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 2.
•treated (eg, cured) carcinoma in situ of the cervix with no evidence of
disease within
5 years of the Screening Visit.
17.The subject has a diagnosis or history consistent with
Antiphospholipid Syndrome.
18.The subject has any history of arterial or venous thrombosis.
19.The subject has a history or current diagnosis of peripheral
neuropathy (sensory or motor) ≥ Grade 2.
20.The subject has a presence of active uveitis or any other
ophthalmological finding that in the opinion of the Investigator is
clinically significant.
21.The subject has non-SLE driven inflammatory joint or skin disease or
overlap syndromes as the primary disease.
22.Laboratory criteria as defined in the protocol
For Long-term Extension Phase only:
23. Subjects will not be eligible to enter the long-term extension phase if
they required an increased dose of immunosuppressant medication
above the maximum dose permitted in the protocol during the last 2
months of the active treatment phase.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
SLEDAI 2K
CLASI
BILAG
PGA
Joint Counts
Fatigue
Corticosteroid Reduction
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
SLEDAI 2K: Week 24
CLASI: Week 24
BILAG: Week 24
Joint Counts: Week 24
PGA: Week 24
Fatigue: Week 24
Corticosteroid Reduction: Week 24 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 43 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Brazil |
| Canada |
| Colombia |
| Mexico |
| Russian Federation |
| Serbia |
| United States |
| Belgium |
| Germany |
| Hungary |
| Italy |
| Poland |
| Spain |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The End of Trial is defined as either the date of the last visit of the last subject to complete the posttreatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 5 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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