A Study of Apabetalone in Subjects With Long -COVID

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Post-Acute COVID-19 Syndrome
• Intervention / Treatment: Drug: Apabetalone

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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Omar Hamed; Phone Number: (+971)429704901; Email: Omar.Hamed@pdc-cro.com
• Study Contact Backup: Name: Moaz Rashad; Phone Number: (+971)581154600; Email: moaz.rashad@pdc-cro.com

Study Locations

• Jordan
  • Amman, Jordan
    • Not yet recruiting
    • The Speciality Hospital
    • Contact: Mohammed Hasan Jafar, MD; Phone Number: (+962)795112543; Email: r.elayyan70@gmail.com
• Saudi Arabia
  • Al Mubarraz, Saudi Arabia
    • Not yet recruiting
    • MNGHA- King Abdulaziz Hospital
    • Contact: Maram Al Subaiee, MD; Phone Number: (+966)-542725431; Email: CTS_feasibility@MNGHA.MED.SA
• United Arab Emirates
  • Dubai, United Arab Emirates
    • Recruiting
    • Al Kuwait Hospital
    • Contact: Suad Hannawi, MD; Phone Number: +971 50 551 6624; Email: suadhannawi@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

   -

   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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apabetalone; apabetalone selectively binds to the second bromodomain [BD2] of bromodomain extra terminal (BET) proteins, curbing the transcription of multiple disease associated genes that promote vascular inflammation, complement, acute phase response (APR), fibrosis, dyslipidemia, and vascular calcification.	Drug: Apabetalone; 100-mg capsule, twice daily oral administration with meals; Other Names: RVX000222

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patient acceptable symptom state (PASS)	The PASS assessment will consist of a single question phrased verbally by the delegated administrator as " Taking into account all your symptoms in daily life and your functional impairment, do you consider that your current state is satisfactory?". The response options are "Yes" or "No".	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long COVID Symptom and Impact tools (LCST/LCIT)	These questionnaires will be presented to the subjects in paper format as a patient-reported instrument. Subjects indicate with a check mark which of the 53 symptoms they have experienced in the last 30 days. Symptoms are scored as the number checked by the subject (0-53) The disease's impact on their lives over the past 30 days is scored from the responses to 6 questions. Subjects will answer using a numeric scale ranging from 0 (no impact) to 10 (maximal impact)	90 days
Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form 7a (SF-7a)	The PROMIS F-7a SF consists of seven items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week (NIH, 2007).	90 days
Baseline Dyspnea Index (BDI) & Transition Dyspnea Index (TDI)	The BDI and TDI are Interviewer-administered ratings of severity of dyspnea	90 days
Post-COVID-19 Functional Status (PCFS) Scale	The PCFS is an ordinal scale of 5 steps ranging from Grade 0 (No functional limitations) to Grade 4 (Severe functional limitations). This scale will be self-administered by the patient	90 days
DePaul Symptom Questionnaire - Post-Exertional Malaise Short Form (DSQ-PEM)	Post-exertional malaise (PEM) is a key symptom of chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) will be used in this study to measure this symptom for patients with Post Covid Condition	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of inflammation	Change in biomarkers of inflammation from baseline. Assessed biomarkers will include Interferon (IFN): IFN-a, IFN-b, IFN-g, Interleukins (IL): IL-1a, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-10, IL-10Rb, IL-12b, IL-13, IL-17, IL-18, IL-33, IP-10 and Tumor Necrosis Factor (TNF): TNF-a, TNF-b	Days 1,14,30,60,90
biomarkers associated with Post-COVID-19 Condition and Chronic Fatigue Syndrome	Change in levels of Post-COVID-19 Condition and Chronic Fatigue Syndrome associated proteins. Assessed biomarkers will include: Immune system markers: CD4+, CD8+, CD27+, CD62L+, NKCD57+ and perforin+. Vascular biomarkers: Ang-2, D-dimer, Factor VIII:C, MMP-1, MMP-9, sICAM-1, sVCAM-1, VEGF, VWF:Ag, VWF:pp	Days 1,14,30,60,90
blood transcriptome and plasma proteome and metabolomics	Change in RNA expression attributable to Post-COVID-19 Condition. Micro-RNA's assayed will include hsa-miR146a-5p, hsa-miR-126-3p and hsa-miR-223-3p. SARS-CoV-2-related host RNAs (ACE2/TMPRSS2 receptors, DPP4/FURIN proteases) and RNAs prototypical for memory B-cells and platelets will also be evaluated	baseline in blood cell transcriptome at Day 1, Day 14 and change from baseline in plasma proteome at Days 1,14,30,60,90

Collaborators and Investigators

• Sponsor: Resverlogix Corp
• Investigators: Study Director: Michael Sweeney, MD, Resverlogix Corp

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: September 5, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: RVX222-CS-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No