A Study of the C3 Complement Inhibitor AMY-101 in Adults With Gingivitis

NCT03694444 | Completed Phase 1 FDA Drug

• 1 other identifier: AMY-101/perio1
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 2a Clinical Trial to Assess the Safety and Efficacy of Complement 3 Inhibitor Analog, AMY-101, in Adults with gingivitis. The study is a 3-month randomized, double-blind, split-mouth study of adults with existing chronic periodontal inflammation determined by the level of gingival index and bleeding on probing. The primary endpoint of change in gingival index will be evaluated at 21, 28 and 90 days after initial treatment (baseline treatment). Subjects will also be followed at Day 3, 7, 14, 21, 28 and 90 for safety evaluations. Change in bleeding on probing plaque index, pocket depth, clinical attachment level and GCF levels of pro-inflammatory cytokines and complement factors will be assessed as secondary outcome measures. Composition of subgingival biofilm will be assessed as an exploratory endpoint. Subjects who meet inclusion criteria will be enrolled in the study and sites will be randomized to treatment groups (AMY-101 or placebo) in split mouth design. After clinical assessments and sample collection at baseline, both test and placebo treatments will be administered to each of the interproximal papilla and will be repeated on Day 7 and 14.

Conditions

Gingivitis

Outcome Measures

Primary Outcomes (1)

• Change in mean gingival index (MGI)

  Assessed at 28 days after initial treatment

Secondary Outcomes (11)

• Gingival inflammation

  Assessed at baseline and Days 3, 7, 14, 21, and 28.

• Ulceration in the oral cavity

  Assessed at baseline and Days 3, 7, 14, 21, and 28.

• Oral infections

  Assessed at baseline and Days 3, 7, 14, 21, and 28.

• Changes in mean gingival index

  Assessed at Days 21 and 90

• Changes in mean bleeding on probing (BOP)

  Assessed at baseline and 21, 28 and 90 days

Study Arms (2)

AMY-101 treatment

ACTIVE COMPARATOR

Subjects who meet inclusion criteria will be enrolled in the study and sites will be randomized to treatment groups (AMY-101 or placebo) in split mouth design. In the AMY-101 treatment arm after clinical assessments and sample collection at baseline, test treatments will be administered to each of the interproximal papilla and will be repeated on Day 7 and 14.

Drug: AMY-101

Placebo

PLACEBO COMPARATOR

Subjects who meet inclusion criteria will be enrolled in the study and sites will be randomized to treatment groups (AMY-101 or placebo) in split mouth design. In the placebo arm, after clinical assessments and sample collection at baseline, placebo treatments will be administered to each of the interproximal papilla and will be repeated on Day 7 and 14.

Other: Water for injection

Interventions

AMY-101 DRUG

C3 complement inhibitor

AMY-101 treatment

Water for injection OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Age 18-65 years old.
• Equal to or greater than 18 natural teeth present (excluding third molars).
• Generalized periodontal inflammation determined by modified gingival index and percent bleeding on probing (MGI≥2.0, BOP ≥ 40%).
• In good general health as evidenced by medical history.
• For women of reproductive potential, use of licensed hormonal contraception or barrier methods or abstinence for at least 1 month prior to screening and agreement to use such a method during study participation.
• For men of reproductive potential, agreement to use condoms or other methods to ensure effective contraception with partner.

You may not qualify if:

• Presence of orthodontic appliances (including fixed lingual retainer).
• A soft or hard tissue tumor of the oral cavity.
• Carious lesions requiring immediate treatment.
• Participation in any other clinical study within 30 days of screening or during the study.
• Antibiotic therapy within the last 30 days.
• Chronic use (≥3 times/week) of anti-inflammatory medications \[e.g., non-steroidal anti-inflammatory drugs (NSAIDs), steroids\]. Low dose (\<325 mg) aspirin is allowed.
• Immune compromised subjects (e.g., subjects with HIV infection, neutropenia, complement deficiency, etc.).
• Any medical history or any concomitant medication that might affect the assessment of the study treatment or periodontal tissues, such as diabetes (irrespective of level of control), rheumatoid arthritis, Crohn's disease, nifedipine, phenytoin (Dilantin), anticoagulant medications (e.g., warfarin \[Coumadin\] etc.), ongoing cancer treatment either with radiation or chemotherapy.
• Involvement in the planning or conduct of the study.
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or interfere with interpretation of the subject's study results.
• Pregnancy or lactation.
• Uncontrolled chronic diseases (e.g., kidney disease, COPD, pulmonary fibrosis, Hepatitis C)
• Autoimmune disorders (Down's Syndrome, Sjogren's Disease, Psoriasis, Chediak-Higashi Syndrome)
• Conditions requiring antibiotic prophylaxis.
• Periodontal therapy within the past one year.

Sponsors & Collaborators

• Amyndas Pharmaceuticals S.A.: lead

Study Sites (1)

Forsyth Institute

Cambridge, Massachusetts, 02142, United States

Location

Related Publications (2)

• Hasturk H, Hajishengallis G; Forsyth Institute Center for Clinical and Translational Research staff; Lambris JD, Mastellos DC, Yancopoulou D. Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. 2021 Dec 1;131(23):e152973. doi: 10.1172/JCI152973.

  PMID: 34618684 DERIVED

• Hajishengallis G, Hasturk H, Lambris JD; Contributing authors. C3-targeted therapy in periodontal disease: moving closer to the clinic. Trends Immunol. 2021 Oct;42(10):856-864. doi: 10.1016/j.it.2021.08.001. Epub 2021 Sep 2.

  PMID: 34483038 DERIVED

MeSH Terms

Conditions

Gingivitis

Interventions

AMY-101; Water; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

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: September 23, 2018
• First Posted: October 3, 2018
• Study Start: July 22, 2019
• Primary Completion: August 30, 2020
• Study Completion: October 30, 2020
• Last Updated: February 21, 2021

Record last verified: 2021-02

Locations

US (1)