Clinical trial NCT03626311: Omega-3 Replacement With Krill Oil in Disease Management of SLE
Official title: A Double-Blind, Placebo-Controlled Randomized, Multicenter Study to Assess Changes in Omega-3 Index in Erythrocytes and Health Benefit After 24 Weeks of Daily Consumption of AKBM-3031 (Omega-3 Phospholipids From Krill), Followed by a 24 Week Open-Label Extension, in Patients With Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Lupus
SLE
Lead sponsor: Aker BioMarine Human Ingredients AS
Sponsor class: INDUSTRY
Collaborators: name: Ampel BioSolutions, LLC
First posted: 2018-08-13
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible patients will be randomized (1:1) to receive either AKBM-3031 or placebo during the randomized period.The randomized subjects will take (4)1 gram capsules of product or placebo every day, (2) 1 gram capsules in the morning and (2) 1 gram capsules in the evening, for a total of 4 grams per day for the first 24 weeks (randomized period). All subjects may continue to a 24-week extension (Open Label Extension) of open-label AKBM-3031, 4 grams/day. The total study duration per subject is 48 weeks. With about 4 months for site activation and 12 months for enrollment, the entire study is expected to complete in approximately 116 weeks.
Primary purpose: SUPPORTIVE_CARE

Brief summary: A randomized, double-blind controlled, multicenter study in SLE patients given AKBM-3031or placebo for 24 weeks (randomized period) and followed by an open label extension (OLE) treatment with AKBM-3031 for the next 24 weeks. Patients will be maintained on stable doses of background medications, except for glucocorticoids. Decreases in doses of glucocorticoids will be encouraged during the first 20 weeks of both the randomized and open label extension portions of the trial. Stable doses of glucocorticoids and other background medications are required during weeks 20-22 and 44-48.If indicated by the PI, brief increases in corticosteroids are permitted during the first 20 weeks of both the blinded and open label extension portion of the trial. The increase in prednisone (or equivalent) dose is limited to 2X the back-ground level to a maximum of20 mg/day for a maximum of 1 week (7 days) or to a single administration of intravenous methylprednisolone or equivalent at a maximum dose of 500mg. Stable doses of glucocorticoids and other background medications are required during weeks 20-22 and 44-48


Eligibility criteria: Inclusion Criteria:

1. Male or female aged at least 18 years old.
2. Capable of giving written consent on an Institutional Review Board or IRB-approved Informed Consent Form prior to any study-specific evaluation
3. Have a clinical diagnosis of SLE with at least 4 of the 11 American College of Rheumatology (ACR) criteria as modified in 1997 or meeting SLICC criteria
4. SLE activity (SLEDAI ≥6)
5. On a stable SLE treatment regimen consisting of a stable dosage of any of the following medications for a period of at least 30 days prior to Baseline (i.e., day of 1st dose of study agent):

   1. Corticosteroids. Corticosteroids (\< 20 mg prednisone or equivalent per day)
   2. Hydroxychloroquine or equivalent anti-malarial
   3. Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium at no more than 2 grams/day), calcineurin inhibitors (e.g., tacrolimus,cyclosporine)
   4. Belimumab dose must be stable for 60 days prior to Baseline
   5. Cyclophosphamide dose must be stable for the last 90 days prior to Baseline
   6. Have not received rituximab within 6 months
6. Have a low habitual consumption of fatty fish and seafood, defined as a frequency of twice per month or less; see Addendum 1 for a list of fish and seafood considered to be fatty.

Exclusion Criteria:

Patients are excluded from the study if any of the following criteria are met:

1. Have rapidly progressive neurologic or renal disease
2. Currently taking an omega-3 prescription drug (e.g. Lovaza®, Vascepa®, etc.) or as medical food (e.g. Vascazen®, Vayarin, Onemia™etc.)
3. Present or recent use (within 3 months of screening) of any OTC fish or krill oil dietary supplement., or any long-chain omega-3 fatty acid dietary supplement (e.g.,MegaRed)
4. Have severe lupus kidney disease (defined by proteinuria \> 6 gm/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine \> 2.5mg/dL)
5. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not related to SLE (i.e., diabetes, cardiovascular, pulmonary, hematologic, gastrointestinal, neurological, or infectious) which, in the opinion of the treating physician, could confound the results of the study or put the patients at undue risk
6. Have received intravenous glucocorticoids at a dosage of ≥ 500 mg daily within the past month
7. Require anti-coagulation with coumadin, clopidogrel, dalteparin, dypyridamole, enoxaparin, heparin or ticlopidine. Low dose aspirin (\<325 mg/day) is permitted.
8. Receiving orlistat (Xenical, Alli) and have refused to discontinue at baseline and throughout the trial.
9. History of allergy to seafood or shellfish
10. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Baseline
11. Are pregnant or lactating
12. Recent participation in a clinical trial with an experimental agent in the past 6 weeks, or 5 half-lives of the study drug, whichever is longer
13. Have a Grade 3 or greater laboratory abnormality based on the Adverse Event Severity Grading Tables (CTCAE), except for the following that are allowed:

    1. Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy
    2. Stable Grade 3 hypoalbuminemia due to chronic lupus nephritis, and not related to liver disease
    3. Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes, or viral hepatitis. If present, any abnormalities in the ALT or Alanine Transaminase and/or AST or Aspartate Transaminase must be \< Grade 2.
    4. Stable Grade 3 neutropenia or stable Grade 3 white blood cell count due to lupus.
14. Patients will be excluded from the study based on the following bone marrow, hepatic and renal function values:

    1. Hemoglobin: \< 8.0 gm/dL
    2. Platelets: \<50,000/mm
    3. ANC \< 1.0 x 103/mm
    4. AST or ALT \>2.5 x Upper Limit of Normal unless related to primary disease.
    5. Creatinine clearance ≤ 25ml/min per 1.73m2

Primary outcomes:
measure: Difference in the ratio of omega-3 to omega-6 measured through lab tests on red blood cells from baseline through the end of the study in patients with generalized lupus.
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Effect of correction of omega-3 deficiency measured by SLE biomarkers of immune function.
timeFrame: Baseline to 24 weeks
measure: Effect of correction of omega-3 deficiency measured by both clinician and patient reported outcomes collected at clinic visits.
timeFrame: Baseline to 24 weeks
measure: Change in health related quality of life measured using the Medical Outcomes study Short Form 36 (SF-36).
timeFrame: Baseline to 24 weeks
measure: Difference of number of patients with reported adverse events or changes in lab parameters while taking AKBM-3031.
timeFrame: Baseline to 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Beverly Hills
country: United States
facility: Wallace Rheumatic Studies Center, LLC
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Rush Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Vancouver
country: Canada
facility: Lupus Clinic-Mary Pack Arthritis Centre
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre-The Montreal General Hospital
state: Quebec
city: Quebec
country: Canada
facility: University of Laval
Study officials:
References: