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Phase Ib Study of SC Milatuzumab in SLE

Primary Purpose

Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

milatuzumab

Placebo

About this trial

This is an interventional treatment trial for Lupus Erythematosus, Cutaneous focused on measuring systemic lupus erythematoses, lupus, SLE

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female ≥ 18 years old
Signed written informed consent before study entry
Diagnosis of SLE by American College of Rheumatology revised criteria (meets ≥ 4 criteria)
Positive ANA (titer ≥ 1:80) at study entry
At least 1 BILAG A or 2 BILAG B scores in any organ/body system and ≥ 6 SELENA-SLEDAI score
Receiving at least 5.0 mg/day oral prednisone (or equivalent) at stable doses for at least 4 weeks prior to study entry
If receiving immunosuppressives or antimalarial agents, at stable doses for at least 4 weeks prior to study entry

Exclusion Criteria:

Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test.
Women of childbearing potential and fertile men not practicing or unwilling to practice birth control during the study
Rituximab, belimumab, other prior antibody, investigational or experimental therapy within 6 months
Allergic to murine, chimeric, humanized or human antibodies
Hematologic abnormalities not attributed to lupus: hemoglobin < 8.0 mg/dL, WBC < 2000/L, ANC < 1500/L, platelets < 50,000/L,
AST, ALT or alkaline phosphatase > 3 times upper limit of normal and not attributed to lupus
Serum creatinine > 2.5 mg/dL, proteinuria > 3.5 g/day
Received live vaccine within 4 weeks
Thrombosis, spontaneous or induced abortion, stillbirth or live birth within 4 weeks
Antiphospholipid antibodies AND a history of thromboembolic events
On oral anticoagulants (not including NSAIDs) within 4 weeks
Active infection with antibiotics within 7 days
Infection requiring hospitalization or herpes zoster treatment within 4 weeks
Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years
Malignancy (except squamous or basal cell carcinoma, cervical CIS) within 3 years (unless approved by the medical monitor)
History of recurrent abortions (2 or more)
Known HIV, hepatitis B or C, other immunosuppressive states
Other concurrent medical conditions that, in the investigator's opinion, could affect the patient's ability to tolerate or complete the study will not be eligible for the study.

Sites / Locations

Cedars Sinai Medical Center-Wallace Rheumatic Study Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Milatuzumab SC 250 mg

Milatuzumab 150 mg SC

Placebo SC

Arm Description

Milatuzumab 250 mg will be administered subcutaneously once weekly for 4 weeks.

Milatuzumab 150 mg will be administered subcutaneously once weekly for 4 weeks.

Placebo will be administered subcutaneously once weekly for 4 weeks.

Outcomes

Primary Outcome Measures

Safety and Tolerability

Will be assessed using laboratory and clinical data comparing baseline lab results and clinical condition to the lab results and clinical condition/adverse events during treatment and follow-up timepoints up to 2 years.

Obtain preliminary evidence of efficacy for patients with active disease.

Will be assessed using the BILAG scoring model for lupus disease activity and symptoms by comparing baseline BILAG measurements against the BILAG measurements obtained during treatment and during follow-up for up to 2 years.

Secondary Outcome Measures

Full Information

NCT ID

NCT01845740

First Posted

April 17, 2013

Last Updated

August 12, 2021

Sponsor

Gilead Sciences

Collaborators

United States Department of Defense

1. Study Identification

Unique Protocol Identification Number

NCT01845740

Brief Title

Phase Ib Study of SC Milatuzumab in SLE

Official Title

A Phase Ib Study of Milatuzumab Administered Subcutaneously in Patients With Active Systemic Lupus Erythematosus (SLE)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

January 2007 (Actual)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

Collaborators

United States Department of Defense

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Milatuzumab will be given subcutaneously at different dose levels once (depending on the dose level) for 4 weeks to determine if milatuzumab helps to control lupus (SLE).

Detailed Description

Milatuzumab or placebo will be given subcutaneously once weekly for 4 weeks to determine if milatuzumab helps to control lupus (SLE). The treatment portion of the study lasts 4 weeks. Then patients are followed for disease activity for at least 12 weeks. If patients respond to the study drug, they may be eligible for one course of retreatment, again followed by 12 weeks of follow-up. Patients who showed a response will continue to be followed at timepoints up to one year after treatment to assess how long the response lasts.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic, Lupus Vasculitis, Central Nervous System, Lupus Nephritis

Keywords

systemic lupus erythematoses, lupus, SLE

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Milatuzumab SC 250 mg

Arm Type

Experimental

Arm Description

Milatuzumab 250 mg will be administered subcutaneously once weekly for 4 weeks.

Arm Title

Milatuzumab 150 mg SC

Arm Type

Experimental

Arm Description

Milatuzumab 150 mg will be administered subcutaneously once weekly for 4 weeks.

Arm Title

Placebo SC

Arm Type

Placebo Comparator

Arm Description

Placebo will be administered subcutaneously once weekly for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

milatuzumab

Other Intervention Name(s)

Milatuzumab is a Cd74 targeted humanized monoclonal antibody.

Intervention Description

Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered subcutaneously once weekly for 4 weeks.

Primary Outcome Measure Information:

Title

Safety and Tolerability

Description

Time Frame

up to 2 years

Title

Obtain preliminary evidence of efficacy for patients with active disease.

Description

Time Frame

up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female ≥ 18 years old Signed written informed consent before study entry Diagnosis of SLE by American College of Rheumatology revised criteria (meets ≥ 4 criteria) Positive ANA (titer ≥ 1:80) at study entry At least 1 BILAG A or 2 BILAG B scores in any organ/body system and ≥ 6 SELENA-SLEDAI score Receiving at least 5.0 mg/day oral prednisone (or equivalent) at stable doses for at least 4 weeks prior to study entry If receiving immunosuppressives or antimalarial agents, at stable doses for at least 4 weeks prior to study entry Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test. Women of childbearing potential and fertile men not practicing or unwilling to practice birth control during the study Rituximab, belimumab, other prior antibody, investigational or experimental therapy within 6 months Allergic to murine, chimeric, humanized or human antibodies Hematologic abnormalities not attributed to lupus: hemoglobin < 8.0 mg/dL, WBC < 2000/L, ANC < 1500/L, platelets < 50,000/L, AST, ALT or alkaline phosphatase > 3 times upper limit of normal and not attributed to lupus Serum creatinine > 2.5 mg/dL, proteinuria > 3.5 g/day Received live vaccine within 4 weeks Thrombosis, spontaneous or induced abortion, stillbirth or live birth within 4 weeks Antiphospholipid antibodies AND a history of thromboembolic events On oral anticoagulants (not including NSAIDs) within 4 weeks Active infection with antibiotics within 7 days Infection requiring hospitalization or herpes zoster treatment within 4 weeks Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years Malignancy (except squamous or basal cell carcinoma, cervical CIS) within 3 years (unless approved by the medical monitor) History of recurrent abortions (2 or more) Known HIV, hepatitis B or C, other immunosuppressive states Other concurrent medical conditions that, in the investigator's opinion, could affect the patient's ability to tolerate or complete the study will not be eligible for the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Wegener, PhD, MD

Organizational Affiliation

Gilead Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cedars Sinai Medical Center-Wallace Rheumatic Study Center

City

West Hollywood

State/Province

California

ZIP/Postal Code

90048

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22404985

Citation

Frolich D, Blassfeld D, Reiter K, Giesecke C, Daridon C, Mei HE, Burmester GR, Goldenberg DM, Salama A, Dorner T. The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression. Arthritis Res Ther. 2012 Mar 9;14(2):R54. doi: 10.1186/ar3767.

Results Reference

background

PubMed Identifier

22271448

Citation

Gupta P, Goldenberg DM, Rossi EA, Cardillo TM, Byrd JC, Muthusamy N, Furman RR, Chang CH. Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas. Blood. 2012 Apr 19;119(16):3767-78. doi: 10.1182/blood-2011-09-381988. Epub 2012 Jan 23.

Results Reference

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PubMed Identifier

22042694

Citation

Alinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, Mani R, Mao Y, Yu B, Quinion C, Towns WH, Chen CS, Goldenberg DM, Blum KA, Byrd JC, Muthusamy N, Praetorius-Ibba M, Baiocchi RA. FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. Blood. 2011 Dec 22;118(26):6893-903. doi: 10.1182/blood-2011-06-363879. Epub 2011 Oct 31.

Results Reference

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PubMed Identifier

1417823

Citation

Santana JM, Grellier P, Rodier MH, Schrevel J, Teixeira A. Purification and characterization of a new 120 kDa alkaline proteinase of Trypanosoma cruzi. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1466-73. doi: 10.1016/0006-291x(92)90467-y.

Results Reference

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PubMed Identifier

21228331

Citation

Alinari L, Yu B, Christian BA, Yan F, Shin J, Lapalombella R, Hertlein E, Lustberg ME, Quinion C, Zhang X, Lozanski G, Muthusamy N, Praetorius-Ibba M, O'Connor OA, Goldenberg DM, Byrd JC, Blum KA, Baiocchi RA. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma. Blood. 2011 Apr 28;117(17):4530-41. doi: 10.1182/blood-2010-08-303354. Epub 2011 Jan 12.

Results Reference

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PubMed Identifier

20574049

Citation

Hertlein E, Triantafillou G, Sass EJ, Hessler JD, Zhang X, Jarjoura D, Lucas DM, Muthusamy N, Goldenberg DM, Lee RJ, Byrd JC. Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells. Blood. 2010 Oct 7;116(14):2554-8. doi: 10.1182/blood-2009-11-253203. Epub 2010 Jun 23.

Results Reference

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PubMed Identifier

19968579

Citation

Berkova Z, Tao RH, Samaniego F. Milatuzumab - a promising new immunotherapeutic agent. Expert Opin Investig Drugs. 2010 Jan;19(1):141-9. doi: 10.1517/13543780903463854.

Results Reference

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PubMed Identifier

19351768

Citation

Stein R, Smith MR, Chen S, Zalath M, Goldenberg DM. Combining milatuzumab with bortezomib, doxorubicin, or dexamethasone improves responses in multiple myeloma cell lines. Clin Cancer Res. 2009 Apr 15;15(8):2808-17. doi: 10.1158/1078-0432.CCR-08-1953. Epub 2009 Apr 7.

Results Reference

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PubMed Identifier

19053886

Citation

Mark T, Martin P, Leonard JP, Niesvizky R. Milatuzumab: a promising new agent for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2009 Jan;18(1):99-104. doi: 10.1517/13543780802636162.

Results Reference

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PubMed Identifier

17875789

Citation

Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang CH, Burton J, Govindan S, Goldenberg DM. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5556s-5563s. doi: 10.1158/1078-0432.CCR-07-1167.

Results Reference

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Phase Ib Study of SC Milatuzumab in SLE

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