Clinical trial NCT06590324: A Study of Apabetalone in Subjects With Long -COVID
Official title: A Phase II, Multi-centre Open Label Study to Assess the Efficacy and Safety of Oral Apabetalone With Background Dapagliflozin in Subjects With Long -COVID-19 (Post-COVID-19 Conditions) and Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Post-Acute COVID-19 Syndrome
Lead sponsor: Resverlogix Corp
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label Study
Primary purpose: TREATMENT

Brief summary: This is an open label, multicentre, phase II clinical trial that aims to assess the efficacy and safety of oral Apabetalone with background dapagliflozin for up to 12 weeks in T2DM patients with a history of probable or confirmed SARS-CoV-2 infection, with symptoms within 3 months from the onset of COVID-19 that last for at least 2 months and cannot be explained by an alternative diagnosis.

Detailed description: This is an open label, multicentre, phase II clinical trial that aims to assess the efficacy and safety of oral Apabetalone with background dapagliflozin for up to 12 weeks in T2DM patients with a history of probable or confirmed SARS-CoV-2 infection, with symptoms within 3 months from the onset of COVID-19 that last for at least 2 months and cannot be explained by an alternative diagnosis. Subjects will be receiving background therapy with dapagliflozin 10 mg daily.

In-person clinic visits will be used to collect data to assess the primary and secondary and exploratory endpoints. There will be 7 in-person visits.

After signing the informed consent form (ICF), and after all screening procedures have been performed, subject data will be reviewed by the Principal Investigator to determine subject eligibility. Eligible subjects will return for Visit 2 (Day 1) and assessments will be performed per the Schedule of Events. Subjects will be enrolled and treatment with Oral Apabetalone 100mg will be initiated. Subjects will be dispensed study drug to be administered at home with meals, twice daily.

Eligibility criteria: Inclusion Criteria:

1. Able and willing to provide written (signed and dated) informed consent before participation in the study, and to comply with scheduled visits, treatment plan, and other study-related procedures to complete the study.
2. Male or female subjects who are ≥ 18 years of age at Screening.
3. Documented diagnosis of T2DM (one or more of the following criteria must be met):

   1. Documented history of T2DM
   2. History of taking diabetes medication
   3. HbA1c ≥6.5% at Screening
4. Must be taking dapagliflozin as part of their diabetes medication, or, based on the Principal Investigator's judgment and indication, be willing to commence sponsor-provided dapagliflozin 10 mg daily for the duration of the study.
5. History of Long-COVID symptoms within 3 months from the onset of COVID-19 that have lasted for at least 2 months. Symptoms are listed in Long Covid Symptom Tool (LCST).
6. A Long Covid Impact Tool (LCIT) score of ≥ 30 at the Screening Visit and at Visit 2 (Day 1)
7. A negative SARS-CoV-2 test at the Screening Visit and at Visit 2 (Day 1)
8. Female subjects of childbearing potential and nonsterile male subjects with female partners of childbearing potential must agree to either remain abstinent or use highly effective non-hormonal methods of contraception throughout the study and at least 30 days after the last dose of study drug has been taken. Subjects must adhere to contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies

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   Exclusion Criteria:
9. Subjects with chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) \<25 mL/min/1.73 m2
10. New York Heart Association Class IV congestive heart failure
11. Evidence of cirrhosis from liver imaging or biopsy, a history of hepatic encephalopathy, esophageal or gastric varices, active hepatitis, or prior porta-caval shunt procedure; chronic liver diseases such as primary biliary cholangitis, untreated hemochromatosis, and primary sclerosing cholangitis
12. Subject meets any of the following laboratory criteria at Screening:

    * Alanine transaminase (ALT) or aspartate transaminase (AST) values \> 1.5x the upper limit of normal (ULN)
    * Total bilirubin \>1.5 × ULN.
    * Evidence of an active hepatitis B virus or hepatitis C virus infection
    * History of a positive test for human immunodeficiency virus (HIV)
13. Subjects taking concomitant cytochrome P450 3A4 strong inducers and/or strong inhibitors, or corticosteroid use \>10 mg daily prednisone or equivalent.
14. Subjects who have received a COVID-19 vaccine or booster in the last 30 days prior to screening (Visit 1).
15. Subject who have participated in a clinical study and received any investigational medication within the last 30 days prior to screening (Visit 1).
16. Female subjects who are pregnant, planning to get pregnant, lactating/breastfeeding, or has a positive urine pregnancy test at the Screening Visit or prior to enrollment at the Day 1 visit.
17. Subjects whose safety may be compromised by study participation or are not, in the opinion of the investigator, able or willing to comply with the protocol.

Primary outcomes:
measure: patient acceptable symptom state (PASS)
timeFrame: 90 days
Secondary outcomes:
measure: Long COVID Symptom and Impact tools (LCST/LCIT)
timeFrame: 90 days
measure: Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a (SF-7a)
timeFrame: 90 days
measure: Baseline Dyspnea Index (BDI) & Transition Dyspnea Index (TDI)
timeFrame: 90 days
measure: Post-COVID-19 Functional Status (PCFS) Scale
timeFrame: 90 days
measure: DePaul Symptom Questionnaire - Post-Exertional Malaise Short Form (DSQ-PEM)
timeFrame: 90 days
Other outcomes:
measure: Biomarkers of inflammation
timeFrame: Days 1,14,30,60,90
measure: biomarkers associated with Post-COVID-19 Condition and Chronic Fatigue Syndrome
timeFrame: Days 1,14,30,60,90
measure: blood transcriptome and plasma proteome and metabolomics
timeFrame: baseline in blood cell transcriptome at Day 1, Day 14 and change from baseline in plasma proteome at Days 1,14,30,60,90
Locations:
city: Amman
country: Jordan
facility: The Speciality Hospital
city: Al Mubarraz
country: Saudi Arabia
facility: MNGHA- King Abdulaziz Hospital
city: Dubai
country: United Arab Emirates
facility: Al Kuwait Hospital
Study officials:
affiliation: Resverlogix Corp
name: Michael Sweeney, MD
role: STUDY_DIRECTOR
References: