Omega-3 Replacement With Krill Oil in Disease Management of SLE

Not Applicable

Completed

• Conditions: Systemic Lupus Erythematosus (SLE)
• Interventions: Other: Placebo; Dietary Supplement: AKBM-3031

• Registration Number: NCT03626311
• Lead Sponsor: Aker BioMarine Human Ingredients AS

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-06
• Study First Submitted QC: 2018-08-08
• Study First Posted: 2018-08-13
• Study Start: 2018-10-23
• Primary Completion: 2021-08-21
• Study Completion: 2021-08-21
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-11
• Last Update Posted: 2021-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	4g/day (2 capsules BID)
AKBM-3031	AKBM-3031	4g/day (2 capsules BID)

Primary Outcome Measures

Name	Time	Method
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.	Baseline to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Change in health related quality of life measured using the Medical Outcomes study Short Form 36 (SF-36).	Baseline to 24 weeks	Both physical component scores (PCS) and mental component scores (MCS) will be assessed. Change in both PCS and MCS will be evaluated over the time of this study. The SF-36 is a patient recorded survey of health related quality of life, consisting of the evaluation of 8 domains, and then scored from 0-100. The higher score correlates to better health-related quality of life. The mean for healthy individuals is 50.
Effect of correction of omega-3 deficiency measured by SLE biomarkers of immune function.	Baseline to 24 weeks
Effect of correction of omega-3 deficiency measured by both clinician and patient reported outcomes collected at clinic visits.	Baseline to 24 weeks
Difference of number of patients with reported adverse events or changes in lab parameters while taking AKBM-3031.	Baseline to 24 weeks	Examples of patient reported adverse events include gastrointestinal symptoms, infection, unexplained bleeding, etc. Examples of lab parameters indicating an adverse event are changes in liver function tests, urinalysis, and hematologic parameters (which could be considered an adverse event).

Trial Locations

Locations (19)

McMaster University Medical Center; 🇨🇦 Hamilton, Ontario, Canada

Lupus Clinic-Mary Pack Arthritis Centre; 🇨🇦 Vancouver, British Columbia, Canada

McGill University Health Centre-The Montreal General Hospital; 🇨🇦 Montréal, Quebec, Canada

University of Laval; 🇨🇦 Quebec, Canada

Wallace Rheumatic Studies Center, LLC; 🇺🇸 Beverly Hills, California, United States

UC Irvine Health; 🇺🇸 Orange, California, United States

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Rush Medical Center; 🇺🇸 Chicago, Illinois, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Northwell Health; 🇺🇸 Great Neck, New York, United States

Feinstein Institute for Medical Research; 🇺🇸 Manhasset, New York, United States

Wake Forest Baptist Health; 🇺🇸 Winston-Salem, North Carolina, United States