Safety and Preliminary Efficacy of Lipoxin Analog BLXA4-ME Oral Rinse for the Treatment of Gingivitis

NCT02342691 | Completed Phase 1 Results DMC

• 2 other identifiers: 16-085-EU01DE026934-01
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to evaluate the safety of an investigational compound, BLXA4-ME, topically applied as a daily oral rinse in adults with gingivitis. Safety will be assessed by the incidence of adverse events, including mucosal inflammation and irritancy and findings from safety labs. Subjects will be monitored for development of periodontitis, and oral flora will be analyzed to detect an increase in opportunistic organisms. The secondary objective is to assess preliminary efficacy of the oral rinse, by monitoring changes in the plaque index (PI), modified gingival index (MGI), bleeding on probing (BOP) and levels of interleukin -1β (IL-1β) in gingival crevicular fluid (GCF). The study comprises three groups in a randomized, placebo-controlled double-blind clinical trial design. The treatment group (1.0 μM BLXA4-ME oral rinse) and the placebo rinse group will each include 50 subjects. The no-rinse control group will consist of 25 subjects. Subjects in the treatment and placebo rinse groups will receive oral rinse (BLXA4-ME or placebo) to be applied once daily after morning teeth brushing. Safety parameters will be assessed before and after 3, 7, 14, 21, and 28 days of treatment. Efficacy parameters will be assessed before and after 14 and 28 days of treatment.

Conditions

Gingival Inflammation

Keywords

Safety and efficacy of BLXA4

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events

  Adverse events will be recorded throughout the study, and may include events reported by subjects or changes observed in oral cavity examinations or vital signs (assessed at baseline, Days 3, 7, 14, 21 and 28). Blood and urine will be collected for safety labs at Days 14 and 28 after product administration, and subjects will undergo close monitoring for mucosal inflammation and irritancy and development of periodontitis, using standard clinical periodontal measurements. Follow-up will also occur at 90 days to assess for adverse events.

  up to 90 days

Secondary Outcomes (3)

• Change in Mean MGI (Baseline and 28 Days)

  28 days

• Change in Percent Bleeding on Probing (Baseline and 28 Days)

  28 days

• Change in PI (Baseline and 28 Days)

  28 days

Study Arms (3)

BLXA4-ME oral rinse

EXPERIMENTAL

The topical oral rinse dosage form of BLXA4-ME (also known as ClinRinse-1) will consist of drug substance prepared at a concentration of 1.0 μM in an aqueous vehicle solution

Drug: BLXA4

Placebo oral rinse

PLACEBO COMPARATOR

The placebo preparation will consist of formulated oral rinse without BLXA4-ME and will be identical to the test rinse in color, appearance and taste

Drug: Placebo oral rinse

No Rinse Control

NO INTERVENTION

The no-rinse control group will use no oral rinse, in order to assess the effect of the rinsing action independent of the active ingredients

Interventions

BLXA4 DRUG

BLXA4-ME is a member of a new class of chemically and metabolically stable lipoxin analogs featuring a replacement of the tetraene unit of native lipoxin-A4 (LXA4) with a substituted benzo-fused ring system. The full chemical name of the BLXA4-ME drug substance is (5S, 6R, E)-methyl 5,6-dihydroxy-8-(2-((R,E)-3-hydroxyoct-1-enyl) phenyl) oct-7-enoate.

BLXA4-ME oral rinse

Placebo oral rinse DRUG

The placebo preparation will consist of formulated oral rinse without BLXA4-ME and will be identical to the test rinse in color, appearance and taste

Placebo oral rinse

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed consent form
• Good general health as evidenced by medical history
• Age 18 - 65
• Must have a stable address and be available for the duration of the study
• Must have a minimum of 20 natural teeth, excluding third molars
• Must have a mean full mouth MGI of at least 2.0
• Must be willing to use prescribed oral hygiene procedures and products
• Medications for chronic conditions must be stable for at least 3 months prior to enrollment
• Women of reproductive potential must use licensed hormonal contraception or double barrier methods
• Men of reproductive potential must agree to use condoms
• Liver function test (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase, and total bilirubin) levels equal to or less than 1.5 times the upper limit of normal
• Serum creatinine levels equal to or less than the upper limit of normal;
• Subjects with complete blood count levels within 10% of the normal laboratory range and erythrocyte sedimentation rate equal to or less than 2 times the upper limit of normal.

You may not qualify if:

• Presence of orthodontic appliances or removable partial dentures
• Presence of a soft tissue tumor of the oral cavity
• Presence of gross plaque or calculus (≥ 75% of tooth surfaces)
• Presence of extensive restorations that could affect the marginal gingiva (at the investigators' discretion)
• Preexisting oral pathology, including carious lesions requiring immediate treatment or ulcerations of the mucosa
• Current participation in another clinical trial or product test
• Pregnant or breast feeding
• Residence in the same household as a subject currently enrolled in the study (due to potential blinding and compliance issues)
• Concomitant endodontic therapy or periodontal therapy other than prophylaxis within the past 6 months
• History of early onset periodontitis or acute necrotizing ulcerative gingivitis
• Chronic disease with concomitant oral manifestations, such as autoimmune or immunosuppressive diseases (e.g., human immunodeficiency virus, severe combined immunodeficiency, neutropenia, juvenile arthritis, systemic lupus erythematosus, sickle cell anemia, Crohn's disease, rheumatoid arthritis, Sjögren's syndrome) or immunocompromised status due to cancer chemotherapy, hematopoietic stem cell or solid organ transplant, head and neck radiotherapy, splenectomy, chronic steroid usage
• Recent history of chronic alcohol consumption of more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer, or five 5 ounce servings of wine per day
• Tobacco use (former tobacco users may be enrolled, provided they have been tobacco-free for one year or more)
• Diabetes mellitus
• Medical conditions that the investigator considers significant and that may interfere with the examination or the safety of the subject

Sponsors & Collaborators

• The Forsyth Institute: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

The Forsyth Institute

Cambridge, Massachusetts, 02142, United States

Location

Related Publications (1)

• Hasturk H, Schulte F, Martins M, Sherzai H, Floros C, Cugini M, Chiu CJ, Hardt M, Van Dyke T. Safety and Preliminary Efficacy of a Novel Host-Modulatory Therapy for Reducing Gingival Inflammation. Front Immunol. 2021 Sep 13;12:704163. doi: 10.3389/fimmu.2021.704163. eCollection 2021.

  PMID: 34589083 DERIVED

MeSH Terms

Conditions

Gingivitis

Condition Hierarchy (Ancestors)

Infections; Gingival Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Results Point of Contact

• Title: Hatice Hasturk
• Organization: Forsyth

hhasturk@forsyth.org

617-892-8499

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 21, 2015
• Study Start: April 1, 2015
• Primary Completion: September 28, 2017
• Study Completion: August 30, 2019
• Last Updated: December 20, 2023
• Results First Posted: December 20, 2023

Record last verified: 2023-11

Locations

US (1)