Assessing the Safety and Efficacy of MYMD1 to Treat Depression in Patients With Post-Acute Sequelae of Coronavirus Disease-2019 (PASC)

Sponsor

Johns Hopkins University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05242003

Collaborator

MyMD Pharmaceuticals, Inc. (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

7.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II, Double-Blind, Randomized, Placebo-Controlled Study to evaluate the effects of the drug MYMD1, a novel Immuno-Metabolic Regulator, for its antidepressant and antianxiety properties, in addition to its anti-inflammatory effects, in patients with Post-Acute Sequelae of Coronavirus Disease-2019. The investigators' hope is that this drug will help treat the depressive and anxiety symptoms in post-COVID-19 patients and any post-COVID-19 inflammatory complications.

The total duration of the study will be a maximum of 40 days-involving enrollment (1 day), an active treatment phase (10 days) during which participants will either receive 300mg of MYMD1, 600mg of MYMD1, or a placebo, and a remote monitoring phase (28 days).

Condition or Disease	Intervention/Treatment	Phase
Depression, Anxiety Inflammation COVID-19	Drug: Placebo Drug: 300mg MYMD-1 Drug: 600mg MYMD-1	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Efficacy of MYMD1, a Novel Immuno-Metabolic Regulator, to Treat Depression in Patients With Post-Acute Sequelae of Coronavirus Disease-2019

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo The placebo will be visibly identical and will be administered by a researcher not involved in the clinical care or participant follow up. Use of placebo as a comparator in this study is justified due to the absence of a suitable approved treatment for the studied indication.	Drug: Placebo Oral tablet, placebo once/day for 10 days
Experimental: Lower Dose Treatment MYMD1 is an orally administered hydroxypropyl methylcellulose (HPMC) capsule containing 150 mg (135 to 165 mg, adjusted for purity) of the MYMD1 drug substance. The MYMD1 drug substance is filled into size 4, HPMC capsules. MYMD1 capsules are packaged into white, 30-cc, round, high-density polyethylene (HDPE) bottles with a size 33 mm polypropylene white child-resistant cap with induction seal.	Drug: 300mg MYMD-1 Two 150mg oral tablets, 300mg total once/day for 10 days Other Names: 88139462
Experimental: Higher Dose Treatment MYMD1 is an orally administered hydroxypropyl methylcellulose (HPMC) capsule containing 150 mg (135 to 165 mg, adjusted for purity) of the MYMD1 drug substance. The MYMD1 drug substance is filled into size 4, HPMC capsules. MYMD1 capsules are packaged into white, 30-cc, round, HDPE bottles with a size 33 mm polypropylene white child-resistant cap with induction seal.	Drug: 600mg MYMD-1 Four 150mg oral tablets, 600mg total once/day for 10 days Other Names: 88139462

Arm

Intervention/Treatment

Placebo Comparator: Placebo

The placebo will be visibly identical and will be administered by a researcher not involved in the clinical care or participant follow up. Use of placebo as a comparator in this study is justified due to the absence of a suitable approved treatment for the studied indication.

Drug: Placebo

Oral tablet, placebo once/day for 10 days

Experimental: Lower Dose Treatment

MYMD1 is an orally administered hydroxypropyl methylcellulose (HPMC) capsule containing 150 mg (135 to 165 mg, adjusted for purity) of the MYMD1 drug substance. The MYMD1 drug substance is filled into size 4, HPMC capsules. MYMD1 capsules are packaged into white, 30-cc, round, high-density polyethylene (HDPE) bottles with a size 33 mm polypropylene white child-resistant cap with induction seal.

Drug: 300mg MYMD-1

Two 150mg oral tablets, 300mg total once/day for 10 days

Other Names:

88139462

Experimental: Higher Dose Treatment

MYMD1 is an orally administered hydroxypropyl methylcellulose (HPMC) capsule containing 150 mg (135 to 165 mg, adjusted for purity) of the MYMD1 drug substance. The MYMD1 drug substance is filled into size 4, HPMC capsules. MYMD1 capsules are packaged into white, 30-cc, round, HDPE bottles with a size 33 mm polypropylene white child-resistant cap with induction seal.

Drug: 600mg MYMD-1

Four 150mg oral tablets, 600mg total once/day for 10 days

Other Names:

88139462

Outcome Measures

Primary Outcome Measures

Change in depressive symptoms as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) [Baseline and weekly, up to 1 month]
MADRS is a 10-item scale that is sensitive to antidepressant efficacy. The ten constituent questions respectively assess: apparent sadness, reported sadness, feelings of tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel emotions, pessimistic thoughts, and suicidal thoughts. Each component is rated by the patient on a scale of 0 (none at all) to 6 (very severe), providing a maximum total score of 60. 0-10: Remission, 11-19: Mild depression, 20-29 moderate depression, 30-60: Severe depression.
Change in depressive symptoms as assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) [Baseline, Weekly, up to 1 month]
The SHAPS consists of 14 confirmatory statements about enjoyable situations typically encountered in daily life cross-culturally. The scale is rated on a 4-point Likert scale: 0 = strongly disagree, 1 = disagree, 2 = agree, 3 = strongly agree, except for five reverse scored items. A score of 2 or less constitutes a "normal" score, while an "abnormal" score is defined as 3 or more.
Efficacy of MYMD1 at the proposed doses as assessed by number of serious complications [Up to 1 month]
Outcome measure will compare the number of participants with or without serious complications using Fisher's exact test.
Safety of MYMD1 at the proposed doses assessed by number of adverse events [Up to 1 month]
The analysis of safety will be done using a modified intention to treat approach considering all randomized and treated participants. Adverse events (AEs) experienced by treated participants in each study arm will be described separately. All the AEs that occur during the study will be included in the data lists and organized according to each patient. Events that are considered to be related to the treatment (possibly, probably, or definitely related to it) will also be included in a table. A table with the list of AEs according to maximum intensity will be provided.

Secondary Outcome Measures

Immunomodulatory role of MYMD1 in ameliorating pro-inflammatory biomarker tumor necrosis factor alpha (TNFα) as assessed by TNFα level [Up to 1 month]
TNFα is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis. Normal values are 75 +/- 15 picograms per milliliter (pg/mL).
Immunomodulatory role of MYMD1 in ameliorating pro-inflammatory biomarker interleukin 6 (IL-6) as assessed by IL-6 level [Up to 1 month]
IL-6 is a proinflammatory cytokine that is elevated during times of inflammation, infection, illness, and in patients with mood disorders. IL-6 is not present or is low in healthy individuals and exact reference ranges vary by lab, with an example normal reference range of 0.31 to 5.00 pg/mL.
Immunomodulatory role of MYMD1 in ameliorating pro-inflammatory biomarker c-reactive protein (CRP) as assessed by CRP level [Up to 1 month]
Most hospitalized patients with COVID-19 have elevated C-Reactive Protein (CRP). CRP increases when inflammation is present and can be measured with a high sensitivity-CRP (hs-CRP) test. Hs-CRP values <1 milligram per liter (mg/L) indicate no inflammation while values >10mg/L indicate inflammation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18+ years of age and able to provide informed consent
Post-acute phase COVID-19 patient with mild, moderate, severe or critical course.
Montgomery-Asberg Depression Rating Scale (MADRS) Scores > 20, indicating moderate to severe depression
Peripheral CRP level ≥5mg/L and/or phenotypic (e.g. comorbid inflammatory bowel disorder, rheumatologic disorder or metabolic syndrome) evidence of inflammatory activation

Exclusion Criteria:

Unable to give informed consent and have no legal representative
Prisoner/institutionalized patient
Under age 18
Female subjects who identify as pregnant, self-reported positive pregnancy testing, or who are breastfeeding during the study period
Inability to tolerate oral medications
Any concurrent treatments (e.g. Dexamethasone or Monoclonal Antibodies) that would make patients unsuitable for inclusion in the view of treatment team
Current smoker or smokeless tobacco user, no use of tobacco with 30 days of study entry