PATCH 2&3:Prevention & Treatment of COVID-19 (Severe Acute Respiratory Syndrome Coronavirus 2) With Hydroxychloroquine

NCT04353037 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2020-0003
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.

Conditions

Coronavirus; Corona Virus Infection

Outcome Measures

Primary Outcomes (2)

• Substudy 1 - Number of COVID-19+ PCR Patients in Self-quarantine Who Are Hospitalized

  Number of COVID-19+ PCR patients in self-quarantine who are hospitalized up to 31 days after beginning HCQ or Placebo

  Until completion of study, 29 to 31 days after beginning treatment.

• Sub Study 2:Number of Health Care Workers Testing Positive at 2 Months

  Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months

  Until completion of study, 2 months after start of treatment.

Secondary Outcomes (6)

• Sub Study 1 - Secondary Infection of Co-inhabitants of COVID-19 Positive PCR Patients in Self-quarantine

  Until completion of study, 29 to 31 days after beginning treatment.

• Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine

  15-17 days after completion of 14 day treatment

• Sub Study 1 - Rate of Negative Tests at End of Treatment for COVID-19 Positive PCR Patients in Self-quarantine

  1-3 days after completion of 14 day treatment

• Sub Study 2:Health Care Workers:Number of Shifts Missed

  up to ~60 days after enrollment

• Sub Study 2:Health Care Workers: Assessment of Any Medical Events That Occur During the ~60 Day Active Period

  Until completion of study, 2 months (~60 days) after start of treatment.

Study Arms (2)

Sub Study 1 Patients

EXPERIMENTAL

Patients tested for COVID-19 who meet symptomology and age requirements for eligibility

Drug: Group 1 HCQ; Drug: Group 2 Placebo

Sub Study 2 Health Care Workers

EXPERIMENTAL

Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months

Drug: Group 1 HCQ; Drug: Group 2 Placebo

Interventions

Group 1 HCQ DRUG

Enrolled participants randomized in Group 1 receive the HCQ drug

Also known as: HCQ Group

Sub Study 1 Patients; Sub Study 2 Health Care Workers

Group 2 Placebo DRUG

Enrolled participants randomized in Group 2 will receive a placebo drug

Also known as: Placebo Group

Sub Study 1 Patients; Sub Study 2 Health Care Workers

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give informed consent
• Subjects meeting the following criteria by Sub-Study:
• Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine.Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
• Sub-Study 2: Currently employed as a health care worker. Health care workers are defined as :
• Medical Doctor (MD)
• Doctor of Osteopathic Medicine (DO)
• Nurse Practitioner (NP)
• Physician's Assistant (PA)
• Registered Nurse (RN)
• other members of the medical care team with significant COVID-19 exposure;
• Health care workers meeting the following criteria:
• asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted);
• scheduled for an average of \>20 hours per week of clinical care over the next 2 months.
• Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
• Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).

You may not qualify if:

• Able to give informed consent
• Subjects meeting the following criteria by Sub-Study:
• Sub-Study 1: 50-75 years of age; self-reporting as having a fever within four days prior to time of enrollment; and not requiring hospitalization. Enrolled individuals will undergo testing for COVID-19 and sent home for self-quarantine. Participant must be willing and able to provide informed consent, agree to testing for COVID-19 at time of enrollment to confirm diagnosis and two weeks at the end of treatment.
• Sub-Study 2: Currently employed as a health care worker (Medical Doctor, MD; Doctor of Osteopathic Medicine, DO; Nurse Practitioner, NP; Physician's Assistant, PA; and Registered Nurse, RN or other members of the medical care team with significant COVID-19 exposure); asymptomatic and presumed negative for COVID-19 (no confirmatory testing conducted); scheduled for an average of \>20 hours per week of clinical care over the next 2 months. Participant must agree to standard clinical guidelines and undergo COVID-19 testing upon the presentation of symptoms indicative of an influenza like illness; if a confirmatory COVID-19 diagnosis is given, participant will be offered to cross-over to HCQ 600 mg qd.
• Willing to report compliance with HCQ in the form of a diary and participate in other forms of self-reporting (e.g., symptom tracker and experience log).
• Subjects are willing and able to go to designated areas for testing of COVID-19/SARS-CoV-2.
• Participant must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Participant must have adequate baseline organ function
• Allergy to hydroxychloroquine
• Pregnant or lactating or positive pregnancy test during pre-medication examination
• Receiving any trial treatment drug for 2019-ncov within 14 days prior to screening evaluation (off label, compassionate use or trial related).
• Known retinal disease including but not limited to macular degeneration, retinal vein occlusion, visual field defect, diabetic retinopathy
• History of interstitial lung disease or chronic pneumonitis unrelated COVID-19.
• Due to risk of disease exacerbation, participants with porphyria or psoriasis are ineligible unless the disease is well-controlled, and they are under the care of a specialist for the disorder who agrees to monitor the Participant for exacerbations.
• Participants with serious intercurrent illness that requires active intravenous therapy, intense monitoring, or frequent dose adjustments for medication including but not limited to infectious disease, cancer, autoimmune disease, cardiovascular disease.

Sponsors & Collaborators

• UnitedHealth Group: lead
• ProHealth Care Associates: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

ProHealth New York

New York, New York, 11042, United States

Location

Related Publications (17)

• Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.

  PMID: 32031570 BACKGROUND

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.

  PMID: 32091533 BACKGROUND

• Ong SWX, Tan YK, Chia PY, Lee TH, Ng OT, Wong MSY, Marimuthu K. Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a Symptomatic Patient. JAMA. 2020 Apr 28;323(16):1610-1612. doi: 10.1001/jama.2020.3227.

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• Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.

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• Zheng Y, Shang J, Yang Y, Liu C, Wan Y, Geng Q, Wang M, Baric R, Li F. Lysosomal Proteases Are a Determinant of Coronavirus Tropism. J Virol. 2018 Nov 27;92(24):e01504-18. doi: 10.1128/JVI.01504-18. Print 2018 Dec 15.

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• Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M, Maes P. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother. 2009 Aug;53(8):3416-21. doi: 10.1128/AAC.01509-08. Epub 2009 Jun 8.

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  PMID: 16115318 BACKGROUND

• de Wilde AH, Jochmans D, Posthuma CC, Zevenhoven-Dobbe JC, van Nieuwkoop S, Bestebroer TM, van den Hoogen BG, Neyts J, Snijder EJ. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84. doi: 10.1128/AAC.03011-14. Epub 2014 May 19.

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• Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

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• Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, DiPaola RS, Lotze MT, White E. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res. 2011 Feb 15;17(4):654-66. doi: 10.1158/1078-0432.CCR-10-2634.

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• Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, Schuchter LM, Torigian DA, Panosian JT, Troxel AB, Tan KS, Heitjan DF, DeMichele AM, Vaughn DJ, Redlinger M, Alavi A, Kaiser J, Pontiggia L, Davis LE, O'Dwyer PJ, Amaravadi RK. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014 Aug;10(8):1391-402. doi: 10.4161/auto.29119. Epub 2014 May 20.

  PMID: 24991838 BACKGROUND

• Rangwala R, Leone R, Chang YC, Fecher LA, Schuchter LM, Kramer A, Tan KS, Heitjan DF, Rodgers G, Gallagher M, Piao S, Troxel AB, Evans TL, DeMichele AM, Nathanson KL, O'Dwyer PJ, Kaiser J, Pontiggia L, Davis LE, Amaravadi RK. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. 2014 Aug;10(8):1369-79. doi: 10.4161/auto.29118. Epub 2014 May 20.

  PMID: 24991839 BACKGROUND

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MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Limitations and Caveats

No healthcare workers had a positive Covid test during the study period so the outcome for missed shifts due a positive Covid result was not measured. Due to low enrollment numbers, only a descriptive analysis was reported and we did not test any of the hypotheses described in the statistical analysis plan.

Results Point of Contact

• Title: Mike Lahm, Director Data Science
• Organization: UnitedHealth Group R&D / Optum Labs

MichaelLahm@uhg.com

302-379-0209

Study Officials

• Deneen Vojta, MD

  UnitedHealth Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: For PATCH 2: participant and care provider are blinded. For PATCH 3: Health care worker is blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Medical Officer, Research and Development

Model Details: Treatment and prevention study

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 20, 2020
• Study Start: April 7, 2020
• Primary Completion: July 11, 2020
• Study Completion: July 11, 2020
• Last Updated: October 19, 2021
• Results First Posted: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 1 year

Locations

US (1)