Back to resultsAT1001 for the Treatment of COVID-19 Related MIS-C
Primary Purpose
Covid19, Multisystem Inflammatory Syndrome in Children
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Larazotide Acetate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- Pediatric patients with or without comorbidity
- Age ≥ 1 month to < 21 years
Confirmed MIS-C by signs and symptoms as detailed by the CDC Health Advisory (https://www.cdc.gov/mis-c/hcp/; May 14, 2020)
- Persistent fever/chills (>38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours); AND
- One or more laboratory parameters (evidence of inflammation); AND,
i) elevated C-reactive protein (CRP) ii) elevated erythrocyte sedimentation rate (ESR) iii) elevated ferritin iv) elevated lactic acid dehydrogenase (LDH) v) elevated d-dimer vi) elevated fibrinogen vii) elevated procalcitonin viii) elevated interleukin 6 (IL-6) ix) increased neutrophils x) reduced lymphocytes xi) low albumin c) Evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological)-MUST include GI symptoms, such as nausea, vomiting, diarrhea and/or abdominal pain; AND, d) No alternative plausible diagnoses; AND e) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test
- Subject (or legal authorized representative) capable of understanding and signing an informed consent form and assent form, when appropriate.
Exclusion Criteria:
- Female participants pregnant and/or lactating.
- Female participant has childbearing potential and is unwilling to use an acceptable method of birth control for the duration of the study.
- Participant has a significant co-morbid disease that by the Investigator's determination would make the participant unsuitable for enrollment, including unstable medical conditions.
- Participation in any other clinical investigation using an experimental drug within 30 days prior to screening or intends to participate in another clinical study while participating in AT1001 MIS-C 101 study.
- Have participated in a blood/plasma donation or blood loss greater than 400 mL within 90 days, or greater than 200 mL within 30 days prior to Screening.
- Known hypersensitivity to any of the formulation components of AT1001.
Sites / Locations
- Massachusetts General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Larazotide Acetate
Arm Description
Matching placebo will be administered orally four times a day (QID) to the standard of care for MIS-C.
AT1001 10 μg/kg/dose up to 500 μg/dose (rounded to the nearest 50 μg) will be administered orally four times a day (QID) to the standard of care for MIS-C.
Outcomes
Primary Outcome Measures
Evaluate the efficacy and safety of AT1001 versus placebo on mitigating symptoms of MIS-C
• To evaluate the efficacy and safety of AT1001 versus placebo in pediatric patients with SARS-CoV-2 infection who experience early signs of MIS-C and are at high risk of progression.
Determine proportion of participants with improvement in MIS-C related GI symptoms and no progression of disease
Improvement in GI symptoms is defined as:
Improvement in PedsQL GI Symptoms Scales score ≥48 hours, as determined by patient or caregiver response.
AND improvement in clinical manifestation of GI symptoms, as documented by complete physical exam or clinical assessment and clinical laboratory tests or imaging.
No Progression of MIS-C is defined as:
No involvement of additional organ involvement, as identified by clinical assessment and clinical laboratory tests or imaging.
AND no new onset of new or worsening GI symptoms for ≥48 hours including nausea, vomiting, diarrhea, loss of appetite, and/or abdominal pain, as determined by patient or caregiver symptom report or worsening PedsQL GI Symptoms Scales scores.
Secondary Outcome Measures
Determine the impact of AT1001 on infectious and inflammatory markers of MIS-C
Secondary aims of this study include determining the impact of AT1001 on infectious and inflammatory markers of MIS-C.
Determine the impact of AT1001 on improvement in MIS-C symptoms for ≥48 hours, as determined by patient or caregiver symptom report on MIS-C Symptom Questionnaire.
Determine the impact of AT1001 on length of stay in hospital (days from baseline to readiness to discharge).
Determine the impact of AT1001 on re-presentation to medical care for MISC-related symptoms after discharge.
Determine the impact of AT1001 on need for escalation of care (eg, transfer from hospital ward to ICU; supplemental oxygen; mechanical ventilation).
Determine the impact of AT1001 on change from baseline in additional organ system(s) involvement during acute presentation/hospitalization, as identified by clinical assessment and clinical laboratory tests.
Determine the impact of AT1001 on change from baseline in levels of IgM, IgG, and IgA antibodies against SARS CoV-2.
Determine the impact of AT1001 on change from baseline in levels of inflammatory markers (CRP, d-dimer, ferritin).
Determine the impact of AT1001 on normalization of SARS-CoV-2 Spike, S1 and nucleocapsid.
Determine the impact of AT1001 on change from baseline in levels of zonulin.
Determine the impact of AT1001 on change in mortality (all causes)
Full Information
NCT ID
NCT05022303
First Posted
August 9, 2021
Last Updated
October 6, 2021
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05022303
Brief Title
AT1001 for the Treatment of COVID-19 Related MIS-C
Official Title
A Phase 2a (Proof of Concept), Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AT1001 for the Treatment of COVID-19 Related Multisystem Inflammatory Syndrome in Children (MIS-C)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 2021 (Anticipated)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary aim of this study is to evaluate the efficacy and safety of AT1001 versus placebo in pediatric patients with SARS-CoV-2 infection who experience early signs of MIS-C and are at high risk of progression.
AT1001 10 μg/kg/dose up to 500 μg/dose (rounded to the nearest 50 μg) or matching placebo will be administered orally four times a day (QID) to the standard of care for MIS-C.
Detailed Description
This is a Phase 2a (Proof of Concept), randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of AT1001 for use in hospitalized pediatric patients diagnosed with MIS-C. Eligible participants (N=20) will be treated with AT1001 or matching placebo orally four times a day (QID) for up to 21 days as an add-on to standard of care.
The study includes three phases:
Screening/Baseline: The main purpose of this phase is to determine if the participant meets entry criterion after obtaining informed consent and obtain baseline assessments.
Treatment: Eligible participants will be treated with AT1001 or matching placebo 10 μg/kg/dose QID up to 500 μg/dose (rounded to the nearest 50 μg) for 21 days as an add-on to standard of care for MIS-C.
Follow-up through 24 weeks: The participant will return for a follow-up visits during weekly clinic visits during Week 1 through Week 3, with monthly telemedicine visits at Week 4, Week 8, Week 16 and Week 20, and clinic visits at Week 12 and Week 24.
Safety monitoring, including physical examination, vitals, and clinical laboratory testing will be performed during the screening phase, periodically during treatment phase and at the follow-up phase. Adverse events and concomitant medications will be recorded during the entire study.
Total duration of the participants' participation in the study is approximately 24 weeks (with 21 days treatment period). Total duration of the study is projected to be 12 months, dependent on enrollment timeline.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Multisystem Inflammatory Syndrome in Children
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Placebo and drug arm (10 μg/kg/dose up to 500 μg/dose)
Masking
ParticipantInvestigator
Masking Description
Participant and investigator blinded, Pharmacy unblinded.
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo will be administered orally four times a day (QID) to the standard of care for MIS-C.
Arm Title
Larazotide Acetate
Arm Type
Experimental
Arm Description
AT1001 10 μg/kg/dose up to 500 μg/dose (rounded to the nearest 50 μg) will be administered orally four times a day (QID) to the standard of care for MIS-C.
Intervention Type
Drug
Intervention Name(s)
Larazotide Acetate
Other Intervention Name(s)
AT1001
Intervention Description
AT1001 10 μg/kg/dose up to 500 μg/dose (rounded to the nearest 50 μg) will be administered orally four times a day (QID) to the standard of care for MIS-C.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered orally four times a day (QID) to the standard of care for MIS-C.
Primary Outcome Measure Information:
Title
Evaluate the efficacy and safety of AT1001 versus placebo on mitigating symptoms of MIS-C
Description
• To evaluate the efficacy and safety of AT1001 versus placebo in pediatric patients with SARS-CoV-2 infection who experience early signs of MIS-C and are at high risk of progression.
Time Frame
24 weeks
Title
Determine proportion of participants with improvement in MIS-C related GI symptoms and no progression of disease
Description
Improvement in GI symptoms is defined as:
Improvement in PedsQL GI Symptoms Scales score ≥48 hours, as determined by patient or caregiver response.
AND improvement in clinical manifestation of GI symptoms, as documented by complete physical exam or clinical assessment and clinical laboratory tests or imaging.
No Progression of MIS-C is defined as:
No involvement of additional organ involvement, as identified by clinical assessment and clinical laboratory tests or imaging.
AND no new onset of new or worsening GI symptoms for ≥48 hours including nausea, vomiting, diarrhea, loss of appetite, and/or abdominal pain, as determined by patient or caregiver symptom report or worsening PedsQL GI Symptoms Scales scores.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Determine the impact of AT1001 on infectious and inflammatory markers of MIS-C
Description
Secondary aims of this study include determining the impact of AT1001 on infectious and inflammatory markers of MIS-C.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on improvement in MIS-C symptoms for ≥48 hours, as determined by patient or caregiver symptom report on MIS-C Symptom Questionnaire.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on length of stay in hospital (days from baseline to readiness to discharge).
Time Frame
24 weeks
Title
Determine the impact of AT1001 on re-presentation to medical care for MISC-related symptoms after discharge.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on need for escalation of care (eg, transfer from hospital ward to ICU; supplemental oxygen; mechanical ventilation).
Time Frame
24 weeks
Title
Determine the impact of AT1001 on change from baseline in additional organ system(s) involvement during acute presentation/hospitalization, as identified by clinical assessment and clinical laboratory tests.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on change from baseline in levels of IgM, IgG, and IgA antibodies against SARS CoV-2.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on change from baseline in levels of inflammatory markers (CRP, d-dimer, ferritin).
Time Frame
24 weeks
Title
Determine the impact of AT1001 on normalization of SARS-CoV-2 Spike, S1 and nucleocapsid.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on change from baseline in levels of zonulin.
Time Frame
24 weeks
Title
Determine the impact of AT1001 on change in mortality (all causes)
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pediatric patients with or without comorbidity
Age ≥ 1 month to < 21 years
Confirmed MIS-C by signs and symptoms as detailed by the CDC Health Advisory (https://www.cdc.gov/mis-c/hcp/; May 14, 2020)
Persistent fever/chills (>38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours); AND
One or more laboratory parameters (evidence of inflammation); AND,
i) elevated C-reactive protein (CRP) ii) elevated erythrocyte sedimentation rate (ESR) iii) elevated ferritin iv) elevated lactic acid dehydrogenase (LDH) v) elevated d-dimer vi) elevated fibrinogen vii) elevated procalcitonin viii) elevated interleukin 6 (IL-6) ix) increased neutrophils x) reduced lymphocytes xi) low albumin c) Evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological)-MUST include GI symptoms, such as nausea, vomiting, diarrhea and/or abdominal pain; AND, d) No alternative plausible diagnoses; AND e) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test
Subject (or legal authorized representative) capable of understanding and signing an informed consent form and assent form, when appropriate.
Exclusion Criteria:
Female participants pregnant and/or lactating.
Female participant has childbearing potential and is unwilling to use an acceptable method of birth control for the duration of the study.
Participant has a significant co-morbid disease that by the Investigator's determination would make the participant unsuitable for enrollment, including unstable medical conditions.
Participation in any other clinical investigation using an experimental drug within 30 days prior to screening or intends to participate in another clinical study while participating in AT1001 MIS-C 101 study.
Have participated in a blood/plasma donation or blood loss greater than 400 mL within 90 days, or greater than 200 mL within 30 days prior to Screening.
Known hypersensitivity to any of the formulation components of AT1001.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lael Yonker, MD
Phone
617-726-8707
Email
lyonker@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Victoria A Kenyon, BA
Phone
617-643-4366
Email
vakenyon@partners.org
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lael Yonker, MD
Phone
617-726-8707
Email
LYONKER@MGH.HARVARD.EDU
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
AT1001 for the Treatment of COVID-19 Related MIS-C
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