The primary objective of this study is to evaluate the safety and efficacy of Larazotide(AT1001) versus placebo in children and adults 7 to ≤50 years of age who present withsymptoms of Long COVID in the presence of SARS-CoV-2 antigenemia. AT1001 (n=32) orplacebo (n=16) will be administered orally four times a day (QID) for 21 days.
This is a Phase 2a randomized, double-blind, placebo-controlled clinical trial to
evaluate the safety and efficacy of AT1001 for use in children and adults with symptoms
of Long COVID in the setting of SARS-CoV-2 antigenemia. Eligible participants (N= 48)
will be treated with AT1001 (n= 32) or matching placebo (n= 16) orally four times a day
(QID) for 21 days. The study will consist of three phases:
I. Baseline Screening Visit
After obtaining informed consent and before starting treatment with Larazotide or
placebo, an initial study visit will be conducted in person to confirm subject
eligibility. Subjects will be asked complete a baseline Symptom Burden Questionnaire™ for
Long COVID (SBQ™-LC) to assess organ involvement and symptom severity. During this
screening visit, a venous blood sample will be obtained to, among other things, assess
for Spike antigenemia and confirm subject eligibility. Additional study procedures
occurring during the baseline/screening phase of this study are outlined in Section 6 of
this protocol. Candidates who are found not to meet inclusion criteria, or those who meet
≥1 exclusion criteria will be terminated from the study and will therefore not be treated
with AT1001 or placebo.
II. Treatment phase
Patients who meet inclusion criteria as stated in Section 4 of this protocol will be
treated with AT1001 or matching placebo at a dose of 250 μg or 500 μg for 21 days. Drug
dose will be determined by weight: patients <25.0 kg will receive 250 μg of Larazotide or
Placebo, and patients ≥25.0 kg will receive 500 μg of Larazotide or Placebo.
Randomization and initial dosing will occur on Visit 1 (Day 1). Visits will then occur on
a weekly basis during the treatment phase and will consist of data and/or specimen
collection. Visit 2 (Week 1) and Visit 3 (Week 2) will take place virtually and will not
involve sample collection. Once the subject has completed 21 days of dosing, Visit 4
(Week 3) will take place in person and require the collection of blood, stool and nasal
swabs. Further detail of study procedures during the treatment phase is provided in
Section 6 of this protocol.
III. Follow-up phase Patients will have two additional virtual follow-up visits after
completing their 21-day course of treatment with the study drug. The first follow up
visit will occur one week after completing the study drug (ie. at week 4), and the second
will occur one month later (ie. at week 8). Week 8 visit will serve as the end of study
visit. Biospecimens will not be collected during the follow-up phase.
Safety monitoring, including physical examination, vitals, and clinical laboratory
testing will be performed during the screening phase and after completion of treatment.
Adverse events and concomitant medications will be recorded during the entire study.
Total duration of the participants' participation in the study is approximately 8 weeks
(with 21 days treatment period). Total duration of the study is projected to be 12-36
months, dependent on enrollment timeline.
Drug: Larazotide Acetate
AT1001 (Larazotide) is a locally acting, non-systemic, octapeptide inhibitor of the
zonulin receptor that has shown efficacy in a large variety of animal models of
inflammation. The effectiveness of AT1001 in controlling paracellular permeability as a
tight junction regulator has been widely demonstrated in animal models both in vitro and
in vivo. In MIS-C, prolonged presence of SARS-CoV-2 in the GI tract leads to release of
zonulin, a biomarker of intestinal permeability, with subsequent trafficking of
SARS-CoV-2 antigens into the bloodstream, leading to hyperinflammation (Yonker, et. al.
2021). Five children treated with AT1001 (through an Emergency Investigational New Drug
request authorized by the FDA) displayed a decrease in plasma SARS-CoV-2 Spike antigen
levels, inflammatory markers, and symptom improvement superior to that achieved with the
current standard of treatment for MIS-C (ie. immunoglobulin, systemic steroids) (Yonker,
et. al. 2021) (Yonker, et. al. 2022)
Other Name: AT1001
Drug: Placebo
Matching placebo will be administered orally four times a day (QID) to participants in
the placebo arm.
Inclusion Criteria:
- Age 7 to ≤50 years
- History of SARS-CoV-2 infection, documented by positive PCR and/or antigen test
- SARS-CoV-2 Antigenemia, defined as any detectable presence of full-length spike
protein, nucleocapsid, and/or Spike S1 subunit in plasma
- Ongoing, worsening, new, or recurrent symptoms present ≥4 weeks after SARS-CoV-2
infection.Symptoms include but are not limited to fatigue, malaise, headache,
cognitive impairment, neuropsychiatric symptoms, decreased exercise tolerance, post
exertional malaise, dyspnea, cough, chest pain, palpitations, tachycardia,
gastrointestinal symptoms, musculoskeletal symptoms, fever, lightheadedness,
insomnia and other sleep disturbances, anosmia or dysgeusia, pain, paresthesia,
menstrual cycle irregularities, erectile dysfunction.
Exclusion Criteria:
- Age ≤6 years or >50 years at time of enrollment
- Pregnancy and/or lactation
- Female participant of childbearing age unwilling to use an acceptable method of
birth control for the duration of the study
- Inability to tolerate drug
- Unstable medical conditions or significant co-morbid disease that, by the
investigator's determination would make the participant unsuitable for enrollment
- Participation in any other clinical investigation using an experimental drug within
30 days prior to screening
- Intent to participate in another clinical study while participating in this clinical
trial
- Blood/plasma donation and 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.
- Abnormal baseline liver function as indicated by AST or ALT ≥3 times the upper limit
of normal (ULN), or direct bilirubin ≥2x ULN for age
- Abnormal baseline renal function, defined as glomerular filtration rate ≤50
mL/min/1.73m2
Massachusetts General Hospital
Boston, Massachusetts, United States
Boston Children's Hospital
Boston, Massachusetts, United States
Lael M Yonker, MD
617-724-2890
lyonker@mgh.harvard.edu
Lauren Guthrie, MPH
6176437175
lauren.guthrie@mgh.harvard.edu
Not Provided