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A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis (MISSION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03393013
Recruitment Status : Recruiting
First Posted : January 8, 2018
Last Update Posted : November 24, 2020
Sponsor:
Information provided by (Responsible Party):
Kezar Life Sciences, Inc.

Brief Summary:
This is a Phase 1b/2, multi-center study in which patients will receive KZR-616, administered as a subcutaneous (SC) injection weekly for 13 weeks (Phase 1b) or 24 weeks (Phase 2).

Condition or disease Intervention/treatment Phase
Lupus Nephritis Systemic Lupus Erythematosus Drug: KZR-616 Phase 1 Phase 2

Detailed Description:

The study consists of 2 parts:

Part 1, Phase 1b, is an open-label multiple dose escalation study to evaluate the safety and tolerability of KZR-616 in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis. The Phase 1b part of this study is fully enrolled and active as of September 2020.

Part 2, Phase 2, is an open-label study to evaluate the efficacy and safety of KZR-616 in patients with active proliferative lupus nephritis (LN) to assess the number of patients with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of KZR-616 in Patients With Systemic Lupus Erythematosus With and Without Nephritis
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: KZR-616 60 mg + standard therapy (Phase 2)
60 mg dose level of KZR-616 selected based on data from the Phase 1 dose escalation and administered to patients with active Lupus Nephritis in combination with standard therapy.
Drug: KZR-616
Subcutaneous Injection of KZR-616
Other Name: KZR-616 Lyophile

Experimental: KZR-616 45 mg + standard of care therapy (Phase 1b)
Dose escalation cohort of patients with SLE with and without nephritis to receive 45 mg dose level of KZR-616 in combination with standard of care therapy. This arm is fully enrolled and active.
Drug: KZR-616
Subcutaneous Injection of KZR-616
Other Name: KZR-616 Lyophile

Experimental: KZR-616 60 mg + standard of care therapy (Phase 1b)
Dose escalation cohort of patients with SLE with and without nephritis to receive 60 mg dose level of KZR-616 in combination with standard of care therapy. This arm is fully enrolled and active.
Drug: KZR-616
Subcutaneous Injection of KZR-616
Other Name: KZR-616 Lyophile

Experimental: KZR-616 75 mg + standard of care therapy (Phase 1b)
Dose escalation cohort of patients with SLE with and without nephritis to receive 75 mg dose level of KZR-616 in combination with standard of care therapy. This arm is fully enrolled and active.
Drug: KZR-616
Subcutaneous Injection of KZR-616
Other Name: KZR-616 Lyophile




Primary Outcome Measures :
  1. Phase 1b: To evaluate the safety and tolerability of KZR-616 [ Time Frame: Baseline through 25 weeks ]
    To evaluate the safety and tolerability of KZR-616 when administered as a SC injection weekly for 13 weeks in adult patients with SLE with and without lupus nephritis

  2. Phase 2: To assess the number of patients with lupus nephritis with a 50% reduction in UPCR [ Time Frame: 24 weeks ]
    To assess the number of patients with lupus nephritis with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline


Secondary Outcome Measures :
  1. Phase 1b: Identify Recommended Phase 2 dose levels (RP2Ds) of KZR-616 [ Time Frame: 4 weeks ]
    Determined through assessment of all AEs and any dose limiting toxicities (DLTs)

  2. Phase 1b: To characterize the PK of KZR-616 [ Time Frame: Day 1 ]
    To characterize the pharmacokinetics of KZR-616

  3. Phase 2: To evaluate the safety and tolerability of KZR-616 when administered as a SC injection weekly for 24 weeks [ Time Frame: 37 weeks ]
    Determined through assessment of all AEs

  4. Phase 2: To characterize the efficacy of KZR-616 on parameters of renal function when administered as a SC injection weekly for 24 weeks [ Time Frame: 24 weeks ]
    Determined through assessment of UPCR after 24 weeks when compared to baseline



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

PHASE 1b (fully enrolled):

  • Male or female patients aged 18 to 75 (inclusive)
  • Body Mass Index (BMI) of 18-40 kg/m2
  • Fulfills the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE
  • Have at least one of the following at screening per central lab:

    1. Positive antinuclear antibody (ANA) test (1:80 or higher); or
    2. Anti-double stranded deoxyribonucleic acid (dsDNA) antibodies elevated to above normal (i.e. positive results); or
    3. Anti-Smith antibody elevated to above normal (i.e., positive results)
  • Active SLE as indicated by a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score ≥4 at screening
  • Must have received 1 or more of the following therapies for SLE, each administered at or higher than the minimum dose indicated for at least 12 weeks (unless discontinued or dose adjusted for documented drug-related toxicity or size/weight):

    1. Hydroxychloroquine 200 mg orally daily in combination with prednisone 10 mg daily or equivalent
    2. MMF orally 1 g/day or MPA orally 720 mg/day
    3. Methotrexate orally or SC 15 mg/wk., or leflunomide orally 10 mg/day
    4. Azathioprine (AZA) 100 mg/day or 6-mercaptopurine 50 mg/day (50 or 25 mg/day, respectively, permitted in cases of documented thiopurine methyltransferase [TPMT] polymorphism) orally
    5. Cyclosporine or tacrolimus at doses documented to maintain at least 100 or 5 ng/mL during the required duration, respectively
    6. Cyclophosphamide 500 mg intravenously (IV) every 2 weeks or 500 mg/m2 IV once monthly
    7. Belimumab 10 mg/kg IV every 2 weeks for 3 doses, followed by 10 mg/kg every 4 weeks; or 200 mg SC weekly
    8. Rituximab 1 g IV (may be given as 500 mg twice)
  • Acceptable screening laboratory values of concern, including:

    1. Adequate hematologic criteria
    2. Adequate hepatic function
    3. eGFR ≥40 mL/min/1.73 m2
    4. IgG ≥500 mg/dL
  • Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test prior to the first dose
  • Male patients must use an effective contraception method (e.g. condom with spermicide) from signing the ICF until their completion of the study

PHASE 2 (enrolling):

  • Male or female patients aged 18 to 75 years (inclusive)
  • BMI of ≥18kg/m2
  • Fulfills the 2012 SLICC classification criteria for SLE
  • At least one of the following at Screening per central lab:

    1. Positive ANA test; or
    2. Anti-dsDNA antibodies elevated to above normal; or
    3. Anti-Smith antibody at Screening elevated to above normal
  • Active lupus nephritis with UPCR ≥1.0 measured in 24-hour urine collection
  • Currently receiving one or more immunosuppressive agents
  • Renal biopsy with a histologic diagnosis of LN (ISN/RPS) Classes III, IV-S or IV-G, (A) or (A/C) +/- Class V
  • Acceptable screening laboratory values of concern, including:

    1. Adequate hematologic criteria
    2. Adequate hepatic function
    3. eGFR ≥30mL/min/1.73 m2
    4. IgG ≥500 mg/dL
  • Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline
  • Male patients with a partner of childbearing potential must be either congenitally sterile or surgically sterile (by vasectomy) or willing to use a condom in addition to having their female partner use another form of contraception

Key Exclusion Criteria:

PHASE 1b (fully enrolled):

  • Active central nervous system involvement by autoimmune disease requiring specific therapeutic intervention within 60 days prior to first day of study treatment.
  • Presence of another rheumatic (overlap) disease that may confound clinical assessments in the study.
  • History of antiphospholipid syndrome with thromboembolic event within 12 months of screening or not on an adequate anticoagulation regimen. However, presence of antiphospholipid antibodies alone (without a history of thromboembolic event) is not exclusionary.
  • Receipt of any of the following treatments within the following timeframes before Screening

    1. Systemic corticosteroids ≥ 100 mg prednisone or equivalent: 4 weeks
    2. Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: 4 weeks
    3. Intravenous Immunoglobulin (IVIg): 4 weeks
    4. Other non-biologic immunosuppressive agents, such as cyclosporine, tacrolimus: 4 weeks
    5. Cyclophosphamide: 12 weeks
    6. Cytokine antagonists, including but not limited to interleukin (IL)-1, IL-6, IL-17, IL-12/23, IL-23, interferon (IFN), integrin, and tumor necrosis factor (TNF)-α antagonists: 12 weeks
    7. B-cell-depleting therapies (e.g., rituximab): 24 weeks with levels of circulating cluster of differentiation 19+ (CD19+) B cells within normal limits or 48 weeks if CD19+ count is not available
    8. Belimumab, abatacept, or atacicept: 12 weeks
    9. Other biologics or investigational drugs: 8 weeks or 5 half-lives, whichever is longer
    10. Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis or plasma exchange: 6 weeks
  • Patient has had recent serious or ongoing infection, or risk for serious infection

    1. Acute or chronic infections:

      • Requiring systemic antibiotic, antifungal, or antiviral (antimicrobial) therapy within 14 days of Week 1, Day 1
      • Requiring hospitalization or a course of IV antimicrobial therapy within 24 weeks prior to screening
    2. History of severe and/or disseminated viral infections, and/or opportunistic infections
    3. Known seropositivity for or active infection by human immunodeficiency virus (HIV)
    4. Active, chronic, or resolved hepatitis B or hepatitis C infection
    5. History of progressive multifocal leukoencephalopathy
    6. Active or latent tuberculosis (TB), as suggested by chest x-ray within the 12 weeks prior to screening and/or QuantiFERON®-TB Gold at Screening
    7. Receipt of a live-attenuated vaccine within 12 weeks of first day of study treatment (Week 1, Day 1)
    8. Primary immunodeficiency (unless otherwise considered, in the opinion of the investigator and medical monitor, to confer a clinically insignificant infection risk, such as deficiency in immunoglobulin A (IgA), C1q, C2, or C4 without a history of recurrent infections [3 or more infections in 1 year requiring antimicrobial therapy])
  • History of any concurrent illness that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF
  • Clinical evidence of significant unstable or uncontrolled acute or chronic diseases
  • History of cancer, except for in situ cancer that has been completely excised or has been curatively treated cancer with no sign of disease for > 5 years
  • Major surgery within 4 weeks before signing the ICF or major surgery planned during the study period

PHASE 2 (enrolling):

  • Any of the following: dialysis within 12 months prior to screening, rapidly progressive glomerulonephritis (RPGN), chronic kidney disease not due to lupus nephritis, >50% sclerosed glomeruli on most recent renal biopsy
  • Presence of another rheumatic (overlap) disease that may confound clinical assessments in the study. Secondary sicca or Sjogren's syndrome and antiphospholipid antibody syndrome are allowed
  • History of antiphospholipid syndrome with history of thromboembolic event within 12 months of screening
  • Active central nervous system involvement by autoimmune disease requiring specific therapeutic intervention within 60 days prior to first day of study treatment.
  • Active or chronic infection
  • Patient has or had any of the following:

    1. Progressive multifocal leukoencephalopathy
    2. Active or untreated latent TB, per QuantiFERON-TB Gold at Screening
    3. Receipt of a live-attenuated vaccine within 12 weeks of Baseline (Week 1, Day 1)
    4. Primary immunodeficiency (unless otherwise considered, in the opinion of the investigator and medical monitor, to confer a clinically insignificant infection risk, such as deficiency in IgA, C1q, C2, or C4 without a history of recurrent infections [3 or more infections in 1 year requiring antimicrobial therapy])
    5. Primary hematopoietic cell or solid organ transplant
  • Any active or suspected malignancy or history of documented malignancy within the last 5 years before Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03393013


Contacts
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Contact: Kezar Life Sciences, Inc. (650)822-5600 clinicaltrials@kezarbio.com

Locations
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United States, California
KZR Research Site Recruiting
Los Angeles, California, United States, 990022
KZR Research Site Recruiting
Upland, California, United States, 91786
United States, Florida
KZR Research Site Recruiting
Coral Gables, Florida, United States, 33134
KZR Research Site Recruiting
Miami, Florida, United States, 33136
KZR Research Site Recruiting
Miami, Florida, United States, 33165
KZR Research Site Recruiting
Orlando, Florida, United States, 32810
KZR Research Site Recruiting
Palm Harbor, Florida, United States, 34684
KZR Research Site Recruiting
Tampa, Florida, United States, 33613
United States, New York
KZR Research Site Recruiting
Brooklyn, New York, United States, 11203
KZR Research Site Recruiting
Great Neck, New York, United States, 11021
KZR Research Site Recruiting
Lake Success, New York, United States, 11042
KZR Research Site Recruiting
Manhasset, New York, United States, 11030
KZR Research Site Recruiting
Rochester, New York, United States, 14642
United States, Ohio
KZR Research Site Recruiting
Cincinnati, Ohio, United States, 45267
KZR Research Site Recruiting
Columbus, Ohio, United States, 43210
United States, South Carolina
KZR Research Site Recruiting
Orangeburg, South Carolina, United States, 29118
United States, Tennessee
KZR Research Site Recruiting
Memphis, Tennessee, United States, 38119
United States, Texas
KZR Research Site Recruiting
Baytown, Texas, United States, 77521
KZR Research Site Recruiting
Houston, Texas, United States, 77034
KZR Research Site Recruiting
Houston, Texas, United States, 77084
KZR Research Site Recruiting
Stafford, Texas, United States, 77477
Australia, Victoria
KZR Research Site Recruiting
Clayton, Victoria, Australia, 3168
KZR Research Site Recruiting
Parkville, Victoria, Australia, 3052
Australia, Western Australia
KZR Research Site Recruiting
Nedlands, Western Australia, Australia, 6009
Colombia
KZR Research Site Recruiting
Barranquilla, Atlantico, Colombia
KZR Research Site Recruiting
Bucaramanga, Santander, Colombia
KZR Research Site Recruiting
Cali, Valle Del Cauca, Colombia
Mexico
KZR Research Site Recruiting
Guadalajara, Jalisco, Mexico
KZR Research Site Recruiting
Monterrey, Nuevo Leon, Mexico
KZR Research Site Recruiting
Mexico City, Mexico
Poland
KZR Research Site Not yet recruiting
Poznań, Wielkopolska, Poland
KZR Research Site Not yet recruiting
Szczecin, Woj. Zachodniopomorskie, Poland
KZR Research Site Not yet recruiting
Łódź, Poland
Russian Federation
KZR Research Site Not yet recruiting
Kemerovo, Kemerovo Oblast, Russian Federation
KZR Research Site Not yet recruiting
Krasnoyarsk, Krasnoyarsk Oblast, Russian Federation
KZR Research Site Not yet recruiting
Omsk, Omsk Oblast, Russian Federation
KZR Research Site Not yet recruiting
Rostov-on-Don, Rostov Oblast, Russian Federation
KZR Research Site Not yet recruiting
Saratov, Saratov Oblast, Russian Federation
KZR Research Site Not yet recruiting
Togliatti, Togliatti Oblast, Russian Federation
Ukraine
KZR Research Site Recruiting
Kyiv, Kyiv Governorate, Ukraine, 01135
Sponsors and Collaborators
Kezar Life Sciences, Inc.
Investigators
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Study Director: Kezar Kezar Life Sciences, Inc.
Additional Information:
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Responsible Party: Kezar Life Sciences, Inc.
ClinicalTrials.gov Identifier: NCT03393013    
Other Study ID Numbers: KZR-616-002
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: November 24, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kezar Life Sciences, Inc.:
immunoproteasome inhibition
selective proteasome inhibition
proteasome
lupus nephritis
lupus
nephritis
active proliferative lupus nephritis
open-label
systemic lupus erythematosus
lupus erythematosus
Additional relevant MeSH terms:
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Nephritis
Lupus Nephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Kidney Diseases
Urologic Diseases
Glomerulonephritis