Clinical trial NCT05747534: AT1001 for the Treatment of Long COVID
Official title: Phase 2a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Larazotide (AT1001) for the Treatment of Long COVID in Children and Adults
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Long COVID
Long COVID-19
Post Acute COVID-19 Syndrome
Post Acute Sequelae of COVID-19
Keywords: SARS-CoV-2
Long COVID
Pediatrics
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2023-02-28
Enrollment: 48
Sex: ALL
Minimum age (years): 7
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Drug arm Placebo arm

Subjects \<25.0 kg will receive 250 µg of AT1001 or placebo, and subjects ≥25.0 kg will receive 500 µg of AT1001 or placebo
Primary purpose: TREATMENT

Brief summary: 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 with symptoms of Long COVID in the presence of SARS-CoV-2 antigenemia. AT1001 (n=32) or placebo (n=16) will be administered orally four times a day (QID) for 21 days.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Event Profiling and Time to Symptom Resolution
timeFrame: 8 weeks
Secondary outcomes:
measure: Cytokine profiling, Antigen Testing and Humoral and Cellular Responses
timeFrame: 21 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
References: