Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day
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|ClinicalTrials.gov Identifier: NCT03234465|
Recruitment Status : Terminated (No efficacy could be demonstrated, sponsor decided to prematurely end the study.)
First Posted : July 31, 2017
Results First Posted : November 23, 2020
Last Update Posted : November 23, 2020
The purpose of the study is to evaluate the efficacy, safety and tolerability of topically administered AG013 compared to placebo for reducing Oral Mucositis (OM) in patients undergoing chemoradiation for the treatment of head and neck cancer, as measured by the duration, time to development, and overall incidence of OM during the active treatment phase, beginning from the start of chemoradiation therapy (CRT) until 2 weeks following its completion.
The effect of AG013 on patient-reported symptoms and analgesic use during the active treatment phase, and on the cumulative radiation dose administered before the onset of OM will also be evaluated, as will biomarkers and, in a subset of subjects, the PK (pharmacokinetic) profile of AG013.
|Condition or disease||Intervention/treatment||Phase|
|Oral Mucositis||Biological: AG013 Other: Placebo||Phase 2|
This is a Phase 2, double-blind, placebo-controlled, 2-arm, multi-center trial in which subjects will be randomized in a 1:1 ratio to receive either placebo or AG013. AG013 is a mouth rinse formulation of Lactococcus lactis strain sAGX0085, deficient in the gene coding for thymidylate synthase and producing human TFF1 (Trefoil Factor 1).
Approximately 200 subjects will be enrolled in the study. To protect subjects from unanticipated safety risks, enrollment and treatment in the double-blind study will continue until 10 subjects on AG013 have been recruited. The Data Safety Monitoring Board (DSMB) will review safety data after these 10 subjects on AG013 have completed study treatment. If there are no safety signals identified, the study will continue to recruit the planned number of subjects.
There are 4 study periods as described below: screening, active treatment, short term follow-up and long term follow-up. The screening phase will be no longer than 4 weeks. The active treatment phase will be between 7 and 9 weeks depending on the subject's prescribed CRT (chemoradiation therapy) plan. The short term follow-up phase will be 4 weeks in duration. The long term follow-up will continue until 12 months post CRT. Oral mucositis (OM) assessments will begin at the start of CRT and continue until the subject has completed short term follow-up or until the OM resolves (as defined by a WHO (World Health Organization) score of ≤ 1), whichever comes first. Long term follow-up will continue for 12 months to assure that AG013 does not adversely impact the tumor response to anti-neoplastic therapy.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Topically-applied AG013 for the Attenuation of Oral Mucositis in Subjects With Cancers of the Head and Neck Receiving Concomitant Chemoradiation Therapy|
|Actual Study Start Date :||July 18, 2017|
|Actual Primary Completion Date :||March 31, 2020|
|Actual Study Completion Date :||July 13, 2020|
Experimental: AG013: three mouth rinses/day
Subjects will rinse three times per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
AG013 is made up of genetically modified (GM) bacteria called Lactococcus lactis (L. lactis). Wild type L. lactis are commonly used to produce dairy products including cheeses and milk. To make AG013, the DNA of L. lactis has been changed in the laboratory to secrete a protein called human Trefoil Factor 1 (hTFF1). hTFF1 is normally secreted in saliva and intestines. Trefoil factors have been shown to be important in protecting and healing mucosal tissues, such as the tissue in the mouth, when these tissues are damaged by cancer therapies such as chemotherapy and radiation therapy.
Placebo Comparator: Placebo: three mouth rinses/day
Subjects will rinse three times per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.
- Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4) [ Time Frame: From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT. ]Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03234465
|Study Director:||Alan Joslyn, Ph.D.||Sponsor GmbH|