Efficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS

Postural Orthostatic Tachycardia Syndrome Clinical Trial

— POTS  

Official title:

A Phase 2 Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of Efgartigimod IV in Adult Patients With Post-COVID-19 Postural Orthostatic Tachycardia Syndrome (POTS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05633407
• Other study ID #: ARGX-113-2104
• Status: Completed
• Phase: Phase 2
• Start date: September 23, 2022
• Est. completion date: April 18, 2024

Study information

• Verified date: May 2024
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to investigate the safety, tolerability, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod compared to placebo in participants with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) (post-COVID-19 POTS).

Description:

The study aims to investigate the safety, tolerability, efficacy, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of efgartigimod compared to placebo in participants with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) (post-COVID-19 POTS). Efgartigimod may be a viable treatment option for individuals diagnosed with post-COVID-19 POTS because it has been shown to reduce IgG levels, including IgG autoantibodies, which may underlie some of the autonomic disease manifestations in these patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: April 18, 2024
• Est. primary completion date: April 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Reached the age of consent when signing the informed consent form

2. Capable of providing signed informed consent and complying with protocol requirements

3. Diagnosed with new-onset POTS post-COVID-19 established by the following:

1. History of COVID-19 based on a previous positive test result from either laboratory-confirmed COVID-19 test (eg, a PCR test) or non-laboratory-confirmed COVID-19 test (eg, rapid antigen test); this positive result may be either documented or patient-reported

2. Tilt table or orthostatic vital sign measurements during screening consistent with consensus criteria: sustained HR increase of =30 bpm within 10 min of standing or head up tilt (=40 bpm for individuals aged 18 to 19 years) and/or HR reaching >120 bpm within 10 min; absence of sustained 20 mmHg decrease in systolic blood pressure (SBP)

3. Ongoing symptoms of POTS confirmed by the investigator with at least 3 symptoms in each of the following areas lasting longer than 12 weeks after either diagnosis of COVID-19 or after hospital discharge for COVID-19:

i. Vasomotor symptoms: fatigue, orthostatic intolerance, brain fog, exertional dyspnea, difficulty with concentration, venous pooling, and exercise intolerance ii. Sympathetic over-compensation symptoms: palpitation, heat intolerance, nausea with or without vomiting, insomnia, anxiety, lack of appetite, chest pain, and diaphoresis

4. COMPASS 31 =35 at screening

5. Agree to use contraceptives consistent with local regulations regarding the methods of contraception for those participating in clinical studies and the following:

Male participants: No male contraception is required Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP. Contraceptive requirements.

6. Body mass index (BMI) <35 kg/m2

Exclusion Criteria:

1. Diagnosis of or receiving treatment for the following conditions before COVID-19:

peripheral neuropathy, POTS, myalgic encephalomyelitis encephalitis/chronic fatigue syndrome, Ehlers Danlos syndrome confirmed by genetic testing, autonomic neuropathy, multiple sclerosis, stroke, spinal cord injury, or any known lesions in the central nervous system by imaging or neurological exam

2. History of or currently being treated for clinically significant ongoing cardiac arrythmia, heart failure, myocarditis, pulmonary embolism requiring anticoagulation, pulmonary fibrosis, or critical illness-related polyneuropathy or myopathy

3. Known autoimmune disease that, in the investigator's judgment, would interfere with an accurate assessment of clinical symptoms of post-COVID-19 POTS or puts the participant at undue risk

4. Known HIV disease or common variable immunodeficiency

5. History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for =3 years before the first administration of IMP. Adequately-treated participants with the following cancers may be included at any time:

1. Basal cell or squamous cell skin cancer

2. Carcinoma in situ of the cervix

3. Carcinoma in situ of the breast

4. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)

6. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection or positive SARS-CoV-2 PCR test at screening

7. Positive serum test at screening for an active infection with any of the following:

1. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless associated with a negative HB surface antigen (HBsAg) or negative HBV DNA test

2. Hepatitis C virus (HCV) based on HCV antibody assay unless a negative RNA test is available

3. HIV

8. A medical condition that could confound the results of the study or put the participant at undue risk in the investigator's judgment

9. Clinically significant disease, recent major surgery (within 3 months of screening), or intends to have surgery during the study; or any other condition that in the opinion of the investigator could confound the results of the study or put the participant at undue risk

10. Total IgG <4 g/L at screening

11. Received within 12 weeks or 5 half-lives (whichever is longer) before screening an investigational product

12. Received within 12 weeks before screening either intravenous immunoglobulin (Ig) IV or SC or plasmapheresis/plasma exchange (PLEX)

13. Received a live or live-attenuated vaccine less than 4 weeks before screening

14. Known hypersensitivity to IMP or 1 of its excipients

15. Previously participated in an efgartigimod clinical study and received at least 1 dose of IMP

16. Currently participating in another interventional clinical study

17. History (within 12 months of screening) of or current alcohol, drug, or medication abuse

18. Pregnant or lactating or intends to become pregnant during the study

19. Unwilling to remain on a stable regimen of medications during the study

20. Unwilling to avoid initiation of new physical rehabilitation or other physician-prescribed exercise programs during the 24-week treatment period

Related Conditions & MeSH terms

• Postural Orthostatic Tachycardia Syndrome
• Syndrome
• Tachycardia

Intervention

Drug:
• Efgartigimod
Efgartigimod IV 10 mg/kg infusion qw for 24 weeks. Participants will be randomized to receive efgartigimod IV 10 mg/kg or matching placebo in a 2:1 ratio, respectively
• Placebo
Receive a matching placebo during weekly infusions during a treatment period of 24 weeks. Participants will be randomized to receive efgartigimod IV 10 mg/kg or matching placebo in a 2:1 ratio, respectively

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Harvard Medical School, Brigham and Women's Hospital	Boston	Massachusetts
United States	Case Western Reserve University	Cleveland	Ohio
United States	Apex Trials Croup, LLC	Fort Worth	Texas
United States	Northshore University Health System	Glenview	Illinois
United States	University of California, San Diego Sulpizio Cardiovascular Center	La Jolla	California
United States	Texas Institute of Cardiology	McKinney	Texas
United States	Vandetbilt University Medical Center / Clinical Research Center	Nashville	Tennessee
United States	Stanford Movement Disorder Center	Palo Alto	California
United States	Pioneer Clinical Research	Rosharon	Texas
United States	Metrodora Institute	West Valley City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
argenx	Iqvia Pty Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the efficacy of efgartigimod in reducing the severity of post-COVID-19 POTS symptoms	Change from baseline to week 24 in the Composite Autonomic Symptom Score 31 (COMPASS 31).	Outcome measure is assessed at baseline and week 24.
Primary	Evaluate the efficacy of efgartigimod in reducing the severity of post-COVID-19 POTS symptoms	Change from baseline to week 24 in the Malmo POTS Symptom Score (MaPS).	Outcome measure is assessed at baseline and week 24.
Primary	Evaluate the safety and tolerability of efgartigimod in patients with post-COVID-19 POTS	Incidence and severity of adverse events (AEs), incidence of serious adverse events (SAEs), changes in laboratory test results, vital sign measurements, and electrocardiogram (ECG) results.	Up to 31 weeks
Secondary	Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue	Change from baseline to week 24 in the Patient Global Impression of Severity (PGI-S)	Change from baseline to week 24
Secondary	Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue	Change from baseline to week 24 in the Patient Global Impression of Change (PGI-C)	Change from baseline to week 24
Secondary	Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue	Change from baseline to week 24 in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a	Change from baseline to week 24
Secondary	Evaluate the efficacy of efgartigimod on patient global assessment of disease activity and fatigue	Change from baseline to week 24 in the PROMIS Cognitive Function Short Form 6a	Change from baseline to week 24
Secondary	Assess the pharmacodynamic (PD) effect of efgartigimod	Absolute values, changes from baseline, and percent reduction from baseline in total IgG levels	From Baseline to week 24
Secondary	Assess the pharmacokinetic (PK) profile of efgartigimod	Efgartigimod serum concentration-time profile	From Baseline to week 24
Secondary	Assess the immunogenicity of efgartigimod	Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod	From Baseline to week 24