Baminercept, a Lymphotoxin-Beta Receptor Fusion Protein, for Treatment of Sjögren's Syndrome

NCT01552681 | Terminated Phase 2 Results DMC

• 1 other identifier: DAIT ASJ02
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of the study is to find out if the experimental study agent, baminercept, is effective in treating patients with Sjögren's syndrome. The study will also determine if the study agent can be safely given to patients with Sjögren's syndrome; examine how it affects symptoms of the disease; and attempt to understand how baminercept affects the underlying mechanisms of Sjögren's syndrome and the immune system.

Conditions

Primary Sjögren's Syndrome

Keywords

baminercept treatment

Outcome Measures

Primary Outcomes (1)

• Change From Screening in Stimulated Whole Salivary Flow at Week 24

  After an unstimulated salivary flow assessment the participant was administered a single 5-mg dose of pilocarpine to stimulate saliva production. One hour after the administration of pilocarpine the participant spit into a preweighed 50-cm centrifuge tube for 15 minutes. The sample was weighed to determine the volume (1 g = 1 mL) of saliva. The volume of saliva (mL) was divided by the duration of the test (minutes) to calculate the stimulated salivary flow rate (mL/min). Change from screening was computed as the value at Week 24 minus the screening value. A positive value in change from screening indicates an improvement and a negative value indicates worsening.

  Screening to Week 24

Secondary Outcomes (21)

• Change From Screening in Stimulated Whole Salivary Flow at Week 48

  Screening to Week 48

• Change From Screening in Unstimulated Whole Salivary Flow at Week 24

  Screening to Week 24

• Change From Screening in Unstimulated Whole Salivary Flow at Week 48

  Screening to Week 48

• Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 24

  Baseline to Week 24

• Percent of Subjects Classified as Responders According to the Patient Self-Assessment of Fatigue, Overall Dryness, and Joint Pain at Week 24

  Week 24

Study Arms (2)

Baminercept

EXPERIMENTAL

Subcutaneous injections of 100 mg every week for 24 weeks

Biological: Baminercept

Placebo

PLACEBO COMPARATOR

Subcutaneous injections of matched placebo every week for 24 weeks

Other: Placebo

Interventions

Baminercept BIOLOGICAL

Subjects randomized to baminercept (2:1) will receive 24 weekly injections of 100 mg administered subcutaneously starting at the Day 0 visit and ending at Week 23.

Also known as: lymphotoxin-beta receptor-immunoglobulin fusion protein

Baminercept

Placebo OTHER

Subjects randomized to placebo will receive 24 weekly injections of 100 mg administered subcutaneously starting at the Day 0 visit and ending at Week 23.

Also known as: baminercept placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent;
• Between the ages of 18-75 years (inclusive);
• Body weight ≥ 40 kg;
• Meets the revised European criteria proposed by the American-European Consensus Group for primary Sjögren's Syndrome at screening. These criteria include 3 of the following 4 items:
• ocular symptoms;
• oral symptoms;
• Schirmer's I test showing less than 6 mm of wetting per five minutes in at least one eye, or filamentary keratitis on slit lamp examination, or positive lissamine green staining; or
• diminished salivary production (unstimulated whole salivary flow rate ≤ 1.5 mL/15 min); PLUS, either:
• a positive test for serum SS-A and/or SS-B antibodies, or
• focal lymphocytic sialadenitis, with a focus score ≥ 1.0 per 4 millimeters \^2(mm\^2) on minor salivary biopsy.
• Stimulated salivary flow of ≥ 0.1 mL/minute (min) (at screening);
• Has one or more of the following systemic manifestations of Sjögren's Syndrome that are not life-threatening:
• fatigue (as measured by \> 50 mm on a 100 mm VAS);
• joint pain (as measured by \> 50 mm on a 100 mm VAS);
• peripheral neuropathy (documented by nerve conduction velocity study);

You may not qualify if:

• Has an active infection excluding superficial cutaneous fungal or viral infections;
• Has a chronic or persistent infection that might be worsened by immunosuppressive treatment (e.g., human immunodeficiency virus \[HIV\], hepatitis B, hepatitis C, or tuberculosis);
• History of TB or positive intradermal skin test for purified protein derivative (PPD); positive Mantoux test defined as 10 mm of induration (size of raised bump, not redness), or equivalent positive TB test result, as per country clinical standards, during the screening period. Subjects whose PPD induration is ≥ 5 mm but \< 10 mm are eligible for the study if they had a negative chest x-ray during the screening period. There must be no other clinical evidence of TB on physical examination of the subject. Note: Subjects who have had prior adequate prophylaxis treatment for latent TB with an appropriate course of isoniazid or equivalent, per country standards, are not excluded from study participation. PPD should not be administered within 6 weeks of a live-virus vaccine;
• History of recurrent significant infections or occurrence of a serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within twelve weeks prior to Day 0;
• Receipt of live vaccine within six weeks prior to Day 0;
• History or presence of primary or secondary immunodeficiency;
• History of any life-threatening allergic reactions;
• Is a pregnant or nursing female;
• Ongoing anticoagulant therapy, which is a contraindication for labial salivary biopsy or tonsil biopsy;
• Concurrent use of anticholinergic agents, such as tricyclic antidepressants, antihistamines, phenothiazines, antiparkinsonian drugs, anti-asthmatic medications, or gastrointestinal (GI) medications that cause xerostomia in more than 10% of patients;
• Treatment with any of the following within the defined period prior to Screening:
• years for rituximab;
• weeks for cyclophosphamide;
• weeks for azathioprine, cyclosporine, methotrexate, or mycophenolate mofetil;
• weeks for intravenous immunoglobulin;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator
• Biogen: collaborator

Study Sites (9)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

St. Francis Hospital and Medical Center

Hartford, Connecticut, 06105, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Medical Institute

Baltimore, Maryland, 21224, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Related Publications (1)

• St Clair EW, Baer AN, Wei C, Noaiseh G, Parke A, Coca A, Utset TO, Genovese MC, Wallace DJ, McNamara J, Boyle K, Keyes-Elstein L, Browning JL, Franchimont N, Smith K, Guthridge JM, Sanz I, James JA; Autoimmunity Centers of Excellence. Clinical Efficacy and Safety of Baminercept, a Lymphotoxin beta Receptor Fusion Protein, in Primary Sjogren's Syndrome: Results From a Phase II Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2018 Sep;70(9):1470-1480. doi: 10.1002/art.40513. Epub 2018 Jul 18.

  PMID: 29604186 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)

MeSH Terms

Interventions

baminercept

Limitations and Caveats

Randomization was prematurely stopped in July 2014 due to study product expiration. 52 of the 72 planned subjects were randomized.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• E. William St. Clair, MD

  Duke University

  STUDY CHAIR

• Judith A. James, MD

  Oklahoma Medical Research Foundation

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 13, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 14, 2019
• Results First Posted: March 23, 2016

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

US (9)