Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2017-001489-53-ES
• Date of registration: 14/03/2018
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
• Scientific title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Subjects with Active Systemic Lupus Erythematosus - LOTUS
• Date of first enrolment: 12/06/2018
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001489-53
• 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: yes; 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): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Bulgaria, China, Colombia, Ecuador, Germany, Hungary, Japan, Korea, Republic of, Lithuania, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Taiwan, Ukraine, United States

Contacts

• Name: -
• Affiliation: PAREXEL International LLC

• Name: -
• Affiliation: PAREXEL International LLC

Key inclusion & exclusion criteria

Inclusion criteria:
• Between 16 (unless restricted by local requirements) and 75 years of age, inclusive.
• Diagnosis of SLE made or confirmed by a physician experienced in the treatment of SLE.
• Documented medical history that subject met the SLICC classification criteria for SLE at least 3 months prior to first dose of study agent.
• At least 1 well-documented unequivocally positive test in medical history and detected during screening, for at least 1 of the following autoantibodies: ANA, anti-dsDNA, and/or anti-Smith.
• Have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.
• Have a CLASI activity score of at least 4 or at least 4 joints with pain and signs of inflammation at screening or at Week 0, or both.
• Demonstrate active disease based on SLEDAI-2K score =6 observed during screening. Must also have SLEDAI-2K =4 for clinical features present at Week 0 prior to randomization.
• Must be receiving one or more of the following protocol-permitted, systemic standard-of-care treatments:
a) Oral glucocorticoids (average daily dose =20 mg of prednisone or equivalent) for =6 weeks and at a stable dose =4 weeks prior to first dose of study agent.
- If currently not using oral glucocorticoids, must not have received them for =6 weeks prior to the first dose of study agent.
b) Antimalarials for =12 weeks and at a stable dose for =6 weeks prior to first dose of study agent
c) If using one or more of the following immunomodulatory drugs, must be receiving for =12 weeks and be on a stable dose for =6 weeks prior to first dose of study agent:
-MMF =2 g/day
-MPA =1.5 g/day
-AZA /6-MP =2 mg/kg/day; up to 100 mg/day for subjects weighing =50 kg
-Oral MTX =25 mg/Week or SC or intramuscular (IM) MTX =20 mg/Week with concomitant folic acid or folinic acid.
If the subject is using concomitantly 2 or more of the immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX), the suitability of the subject to participate in the study must be discussed with the medical monitor and/or sponsor before the subject is randomized.
• Before randomization, a woman must be either:
a. Not of childbearing potential, or
b. Of childbearing potential:
-Practicing a highly effective method of contraception
-Agrees to remain on a highly effective method of contraception throughout the study and for at least 16 weeks after the last dose of study agent.
• A woman of childbearing potential must have a negative urine pregnancy tests
• beta-hCG obtained during screening and at Week 0 before the first dose of study agent.
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 4 months after receiving the last dose of study agent.
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control.
• A man who is sexually active with a woman who is pregnant must use a condom and all men must not donate sperm during the study and for 20 weeks after receiving the last dose of study agent.
• Subjects must have laboratory test results within the following parameters at
screening:
- Hemoglobin =8.0 g/dL (SI: = 80 g/L)
- Lymphocytes =0.5 x 103 /microL (SI: =0.5 GI/L)
- Neutrophils =1.0 x 103 / microL (SI: =1.0 GI/L)
- Platelets =75 x 103 /microL (SI: = 75 GI/L)
- Serum creatinine =1.8 mg/dL (SI: = 159 micromol/L)
- AST and ALTIf any other labs are grade 3 or above, this must be discussed with the
medical monitor
Exclusion criteria:
• Has any unstable or progressive manifestation of SLE that is likely to warrant escalation in therapy beyond permitted background medications
• Has other inflammatory disease that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), PsA, RA/lupus overlap, psoriasis, Crohn’s disease, or active Lyme disease
• Is pregnant, nursing, or planning a pregnancy or planning to father a child while enrolled in the study or within 4 months after receiving the last administration of study agent
• Has received systemic immunomodulatory agents other than those described in inclusion criteria within 3 months prior to the first dose of study agent
• Has used oral cyclophosphamide within 90 days or IV cyclophosphamide within 180 days of starting screening
• Exclusions for treatment with B-cell targeted therapies:
a. Treatment with a single B-cell targeted therapy within 3 months prior to first dose of study agent.
b. Treatment with >1 previous B-cell targeting therapy within 6 months prior to first dose of study agent.
c. Treatment with B-cell depleting therapy within 12 months prior to first dose of study agent, or have evidence of continued B-cell depletion following such therapy
• Has ever received ustekinumab
• Has received prior immunomodulatory biologic therapy not described in Section 8.1.7 of protocol less than 5 half-lives or 3 months, whichever is longer, prior to first dose of the study agent.
• Has received ACTH administered by injection within 1 month prior to the first administration of study agent
• Has received topical cream/ointment preparations of cyclosporine A, or other topical immunomodulatory agents within 4 weeks prior to the first administration of study agent
• Is currently receiving venom immunotherapy
• Subjects likely to require multiple courses of systemic steroids for reasons other than SLE
• Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional admin of glucocorticoids within 6 weeks prior to the first administration of study agent
• BCG vaccination within 12 months of screening
• Live virus or live bacterial vaccination within 16 weeks prior to the first administration of study agent
• History of active granulomatous infection, including histoplasmosis, or coccidioidomycosis
• Chest radiograph within 3 months prior to the first dose that shows an abnormality suggestive of a malignancy or current active infection, including TB
• A nontuberculous mycobacterial infection or opportunistic infection
• A history of, or ongoing, chronic or recurrent infectious disease
• History of HIV antibody positive, or tests positive for HIV at screening
• Hepatitis B infection. Subjects must undergo screening for hepatitis B virus
• Seropositive for antibodies to hepatitis C virus (HCV), unless has 2 negative HCV RNA test results 6 months apart prior to screening and has a third negative HCV RNA test result at screening
• Has experienced a recent single dermatomal herpes zoster eruption within the past 4 months. Has ever had multi-dermatomal herpes zoster or CNS zoster infection
• Within 2 months prior to first administration of study agent, has had a serious infection, or has been hospitalized for an infection, or has been treated with IV antibiotics for an infection. Less serious infections need not be considered exclusionary at the discretion of the Investigator
• History or suspected occurrence of drug-induced lupus
• Has inherited complement def

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Systemic Lupus Erythematosus
MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Stelara
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: USTEKINUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Stelara
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ustekinumab
CAS Number: 815610-63-0
Current Sponsor code: CNTO1275
Other descriptive name: USTEKINUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 52

Secondary Objective: The secondary objectives are to evaluate the following in subjects with active SLE despite receiving one or more standard-of-care treatments:
1. Reduction in SLE flares
2. Improvement in global and organ-specific (mucocutaneous, musculoskeletal, etc) measures of SLE disease activity
3. Glucocorticoid sparing

Primary end point(s): The primary endpoint is the proportion of subjects achieving an SRI-4 composite response at Week 52.

Main Objective: The primary objective is to evaluate the efficacy of ustekinumab in
subjects with active systemic lupus erythematosus (SLE) who have not
adequately responded to one or more standard-of-care treatments.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1.Week 52
2.Week 24
3.Week 52
4.Week 52
5.Week 52
6.Week 52

Secondary end point(s): 1. Time to flare based on the proportion of subjects with a flare occurring at any time after the baseline visit through Week 52, with flare defined as either 1 or more new BILAG A or 2 or more new BILAG B domain scores
2. The proportion of subjects with an SRI-4 composite response at Week 24
3. The proportion of subjects achieving at least a 50% improvement in the number of joints with pain and signs of inflammation at Week 52 in subjects with at least 4 affected joints at baseline
4. The proportion of subjects who achieve reduction in glucocorticoid dose by Week 40 and sustain that reduction through Week 52
5. The proportion of subjects achieving at least a 50% improvement in the CLASI Activity Score at Week 52 in subjects with a CLASI Activity Score of 4 or greater at baseline
6. The proportion of subjects with SRI-4 composite response at Week 52 in the subpopulation who achieved reduction in glucocorticoid dose by Week 40 and sustained that reduction through Week 52

Secondary ID(s)

CNTO1275SLE3001

Source(s) of Monetary Support

Janssen Research & Development

Ethics review

Status: Approved
Approval date: 11/04/2018
Contact: