Phase Ib Study of SC Milatuzumab in SLE

NCT01845740 | Completed Phase 1

• 1 other identifier: IMMU-115-04
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

systemic lupus erythematoses; lupus; SLE

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 2 years

Study Arms (3)

Milatuzumab SC 250 mg

EXPERIMENTAL

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

Drug: milatuzumab

Milatuzumab 150 mg SC

EXPERIMENTAL

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

Drug: milatuzumab

Placebo SC

PLACEBO COMPARATOR

Placebo will be administered subcutaneously once weekly for 4 weeks.

Drug: Placebo

Interventions

milatuzumab DRUG

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.

Also known as: Milatuzumab is a Cd74 targeted humanized monoclonal antibody.

Milatuzumab 150 mg SC; Milatuzumab SC 250 mg

Placebo DRUG

Placebo will be administered subcutaneously once weekly for 4 weeks.

Placebo SC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead
• United States Department of Defense: collaborator

Study Sites (1)

Cedars Sinai Medical Center-Wallace Rheumatic Study Center

West Hollywood, California, 90048, United States

Location

Related Publications (10)

• 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.

  PMID: 22404985 BACKGROUND

• 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.

  PMID: 22271448 BACKGROUND

• 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.

  PMID: 22042694 BACKGROUND

• 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.

  PMID: 1417823 BACKGROUND

• 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.

  PMID: 21228331 BACKGROUND

• 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.

  PMID: 20574049 BACKGROUND

• 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.

  PMID: 19968579 BACKGROUND

• 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.

  PMID: 19351768 BACKGROUND

• 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.

  PMID: 19053886 BACKGROUND

• 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.

  PMID: 17875789 BACKGROUND

MeSH Terms

Conditions

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

Interventions

milatuzumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Autoimmune Diseases; Immune System Diseases; Meningoencephalitis; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Encephalitis; Neuroinflammatory Diseases; Meningitis; Vascular Diseases; Cardiovascular Diseases; Vasculitis; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• William Wegener, PhD, MD

  Gilead Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: May 3, 2013
• Study Start: January 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 19, 2021

Record last verified: 2021-02

Locations

US (1)