Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE)

• ClinicalTrials.gov Identifier: NCT02794285
• Recruitment Status: Active, not recruiting
• First Posted: June 9, 2016
• Last Update Posted: May 19, 2020
• Sponsor: AstraZeneca
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: June 6, 2016
• First Posted Date: June 9, 2016
• Last Update Posted Date: May 19, 2020
• Actual Study Start Date: June 30, 2016
• Estimated Primary Completion Date: December 14, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 24, 2016)

To measure the long-term safety and tolerability of IV anifrolumab by measuring the rates of adverse events of special interest and serious adverse events [ Time Frame: Week 208 ]

Rates of Adverse events of special interest and serious adverse events using incidence rates (ie number of events divided by person-time at risk)

Original Primary Outcome Measures (submitted: June 6, 2016)

To characterise the long-term safety and tolerability of IV anifrolumab [ Time Frame: Week 208 ]

Rates of Adverse events of special interest and Serious Adverse Events

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
• Official Title: A Multicentre, Randomised, Double-blind, Placebo-Controlled Phase 3 Extension Study to Characterise the Long-term Safety and Tolerability of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus.
• Brief Summary: The purpose of this study is to characterise long-term safety and tolerability of intravenous anifrolumab.
• Detailed Description: This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled extension study to characterising the long term safety and tolerability of of an intravenous treatment regimen of anifrolumab versus placebo in subjects with moderately to severely active systemic lupus erythematosus who completed a Phase 3 study (D3461C00004 or D3461C00005) through the 52-week double-blind treatment period.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Active Systemic Lupus Erythematosus

Intervention

• Biological: Anifrolumab
  Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
• Drug: Placebo
  Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses

Study Arms

• Experimental: Anifrolumab
  Anifrolumab
  Intervention: Biological: Anifrolumab
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 16, 2019): 559
• Original Estimated Enrollment (submitted: June 6, 2016): 575
• Estimated Study Completion Date: December 14, 2021
• Estimated Primary Completion Date: December 14, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subjects who have qualified for and received investigational product (anifrolumab or placebo) and completed the treatment period in Studies D3461C00004 or D3461C00005 (through Week 52)
2. Adequate peripheral venous access
3. Females with an intact cervix should have documentation of a Pap smear with no documented malignancy within 90 days before Day 1/Visit 1 or 30 days following Day 1/Visit 1. Since access to a Pap smear may vary by country, the Sponsor recommends that local guidelines for obtaining Pap smears in subjects who have received immunomodulators or immunosuppressive treatment be followed.

4. Meets the following TB criteria:

   1. Negative QuantiFERON®-TB Gold [QFT-G] test result for TB obtained from the study central laboratory at Week 52 of Studies D3461C00004 or D3461C00005; OR
   2. Newly positive QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory. A chest x-ray must be performed. If the chest x-ray shows no evidence of active TB, and the subject has no symptoms or medical history consistent with active TB, the subject must have a retest. If the retest is positive, the subject must start on prophylaxis within 30 days of randomisation but prior to the second dose of investigational product (Visit 2/Week 4); OR
   3. Positive but not newly positive QFT-G test at Week 52 of Studies D3461C00004 or D3461C00005. The subject must have been diagnosed with latent TB and must have documentation confirming initiation of appropriate treatment OR initiate treatment for latent TB within 30 days of randomization, but prior to the second dose of investigational product administration (Visit 2/Week 4)
   4. Newly indeterminate (confirmed on retest unless prior positive QFT G was documented, along with completed treatment for latent TB) or indeterminate but not newly indeterminate QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory with ongoing QFT-G testing for TB according to the Study Plan
5. In the opinion of the Investigator, subject must be able to comprehend the ICF and all protocol related assessments

Exclusion Criteria:

1. Receipt of any of the following within the last 60 days:

   1. Azathioprine >200 mg/day
   2. Mycophenolate mofetil >2.0 g/day /mycophenolic acid >1.44 g/day
   3. Oral, subcutaneous, or intramuscular methotrexate >25 mg/week
   4. Mizoribine >150 mg/day
2. Receipt of any investigational product (small molecule or biologic agent other than anifrolumab) within 4 weeks or 5 half-lives prior to Day 1/Visit 1, whichever is greater

3. Receipt of any of the following:

   1. Any live or attenuated vaccine within 8 weeks prior to Day 1/Visit 1 (administration of killed vaccines is acceptable, the Sponsor recommends Investigators ensure all subjects are up to date on required vaccinations, including influenza [inactivated/recombinant] vaccine prior to study entry)
   2. Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or D3461C00005 and Day 1/Visit 1
4. Active severe SLE-driven renal or neuropsychiatric disease
5. Any underlying condition that predisposes the subject to infection, including history of/current human immunodeficiency virus (HIV) infection
6. Subjects with Hepatitis B core antibody (HBcAb) positivity at enrolment of Studies D3461C00004 or D3461C00005 will be tested every 3 months for Hepatitis B virus (HBV) DNA. To remain eligible in the LTE study, subject HBV DNA levels must remain below the lower limit of quantitation as per the central laboratory.
7. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of Day 1/Visit 1

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Bulgaria, Canada, Chile, Colombia, France, Germany, Hungary, Israel, Japan, Korea, Republic of, Lithuania, Mexico, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Taiwan, Ukraine, United Kingdom, United States
• Removed Location Countries: Belgium, Brazil, Czech Republic, Czechia, Italy, New Zealand, Singapore

Administrative Information

• NCT Number: NCT02794285
• Other Study ID Numbers: D3461C00009
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: PRA Health Sciences

Investigators

• Principal Investigator: Kenneth Kalunian, MD; University of California, San Diego
• Study Director: Raj Tummala, MD; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: May 2020