Phase 2 Trial to Evaluate Safety and Efficacy of CYTO-205 in Mild COVID-19

• ClinicalTrials.gov Identifier: NCT04708327
• Recruitment Status: Not yet recruiting
• First Posted: January 13, 2021
• Last Update Posted: January 13, 2021
• Sponsor: Cytocom, Inc.
• Information provided by (Responsible Party): Cytocom, Inc.

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled study. The aim of the study is to assess the safety and clinical efficacy of low-dose naltrexone in reducing the proportion of higher risk patients who progress from mild COVID-19 to a more severe disease category.

Male and female participants with a confirmed positive SARS-CoV-2 diagnostic test at screening, who are symptomatic with mild COVID-19 (as measured by WHO clinical progression scale, WHOb 2020) and are at high risk for COVID-19 progression will be enrolled. High risk is based on presence of one or more criteria which could include age ≥65 years, increased BMI ≥33 kg/m2, or the presence of certain comorbidities (refer to Section 4 for complete eligibility criteria).

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: Naltrexone Hydrochloride	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double-blind
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-controlled, Phase 2 Study to Evaluate Safety and Efficacy of CYTO-205 (Low-dose Naltrexone) in Adult Patients With Mild COVID-19 Infection Who Are at High Risk for Disease Progression
• Estimated Study Start Date: April 2021
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: April 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Naltrexone Hydrochloride; naltrexone hydrochloride capsules 4.5 mg each
Experimental: CYTO-205 22.5 mg	Drug: Naltrexone Hydrochloride; naltrexone hydrochloride capsules 4.5 mg each
Experimental: CYTO-205 45 mg	Drug: Naltrexone Hydrochloride; naltrexone hydrochloride capsules 4.5 mg each

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients who demonstrate progression of COVID-19 disease [ Time Frame: Day 1 to Day 30 ]
   Progression of COVID-19 disease based on the WHO clinical progression scale (WHOb2020)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age >18 at the time of informed consent
2. Able to understand and provide informed consent in either English or Spanish

3. At high risk for COVID-19 disease progression by fulfilling at least ONE of the following criteria at Screening:

   1. Age ≥65 years
   2. Has a diagnosis of chronic pulmonary disease requiring daily treatment (e.g. COPD, chronic persistent asthma, cystic fibrosis, chronic bronchitis)
   3. Has a diagnosis of chronic heart disease
   4. Has a diagnosis of diabetes (type 1 or type 2) requiring oral therapy and/or insulin therapy
   5. Has hypertension requiring at least one oral medication for treatment
   6. Has a body mass index (BMI) of ≥33 kg/m2
   7. Has an immunocompromising disease (e.g. HIV infection with CD4 count < 200 cells/mm3)
   8. Is immunocompromised due to daily treatment with ≥20 mg of prednisone or equivalent
   9. Has received a solid organ transplant
   10. Has any chronic condition that, in the opinion of the investigator, places the patient at increased risk for progression of COVID-19
4. Documentation of positive diagnostic test for SARS-CoV-2 (confirmed by PCR assay or other approved diagnostic test) performed with a sample from nares or saliva, collected within 7 days of the Screening visit.
5. Is symptomatic for COVID-19 for no more than 7 days prior to the Screening visit
6. Has a WHO Clinical Progression Scale (WHOb 2020) score of either '2' or '3' at Screening and Randomization

7. Has at least one of the following symptoms at the Screening visit that are new in onset, or if present by history, has worsened during the 7 days prior to Screening:

   · fever, chills, myalgia, arthralgia, headache, fatigue, cough, sore throat, nasal congestion, nausea, vomiting, diarrhea, anosmia or dysosmia, ageusia or dysgeusia

8. If female of child-bearing potential, must agree to use of 2 forms of contraception from Screening to end of the study. Males must agree to use 2 forms of contraception from screening to the end of the study if their partners are of childbearing potential. Acceptable methods of birth control which must be used together are:

   1. Oral or injectable contraceptive and condom, or
   2. IUD and condom, or
   3. Diaphragm with spermicide and condom.
9. Agrees to participate in all in-person visits and remote or home visits as required by the protocol and to provide updated contact information, as necessary.

Exclusion Criteria:

1. Has a WHO Clinical Progression Scale (WHOb 2020) score of '4' or higher at Screening or Enrollment
2. Previous hypersensitivity or allergic reactions to naltrexone
3. Women who are pregnant or lactating or expecting to become pregnant
4. Drugs of abuse screen positive for opiates
5. Patients with history of moderate to severe renal impairment (estimated creatinine clearance < 50 mL/min) or hepatic impairment (Child-Pugh C)
6. Serum ALT or AST value > 3 times the ULN at Screening
7. Serum creatinine value > 2 times the ULN at Screening, or requires renal dialysis
8. Hematology results at Screening showing any one of the following: WBC <2000 cells/mm3 or platelet count <100,000 cells/mm3 or hemoglobin <8.5 Gm/dL
9. Currently receiving chronic daily opioid therapy
10. Use of tocilizumab or other immunomodulator therapy directed to treatment or prevention of COVID-19
11. History of active substance abuse within the 2 years prior to Screening
12. Participation in another clinical trial investigating a treatment for COVID-19
13. Currently hospitalized or under immediate consideration for hospitalization (for any medical reason) at the Screening visit
14. At Screening, has new onset of dyspnea (shortness of breath) or, if previously diagnosed with a chronic lung condition, the severity of dyspnea has increased over patient's historical baseline condition (increased dyspnea should be present continually and not intermittent)
15. Measurement of oxygen saturation at Screening is < 94% on ambient room air
16. Shares a household with a patient currently enrolled in this protocol
17. Patients who refuse biomarker blood draws

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Cytocom, Inc.
• ClinicalTrials.gov Identifier: NCT04708327
• Other Study ID Numbers: CYTO-001
• First Posted: January 13, 2021
• Last Update Posted: January 13, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents