Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects
Condition: COVID-19; Infectious Disease; Symptomatic COVID-19 Infection Laboratory-Confirmed; SARS CoV 2 Infection
MeSH terms: Infections; Communicable Diseases; COVID-19; Laboratory Infection
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a first in human clinical study to evaluate the safety, pharmacokinetics (PK), and
      pharmacodynamics (PD) of RQ-01. Adult patients who have tested positive for SARS-CoV-2 virus,
      have mild symptom(s) of COVID-19 disease, and who are at low risk for developing moderate or
      severe COVID-19 disease are welcome to participate. The main questions this study aims to
      answer are:

        1. What is the safety profile of RQ-01?

        2. What is the reduction in SARS-CoV-2 ribonucleic acid (RNA) shedding after administration
           of RQ-01?

        3. How effective is RQ-01 versus placebo in reducing COVID-19 symptoms?

      After providing informed consent, subjects will be randomized to RQ-01 (high or low dose) or
      placebo and will be dosed for 3 consecutive days. Throughout the duration of the trial,
      subjects will participate in the following activities: perform rapid antigen and polymerase
      chain reaction (PCR) tests for COVID-19, answer questions about their medical history and
      medications, answer questions about their COVID-19 history and symptoms, conduct a physical
      exam, have their vitals measured, and have bloodwork done.
    

Detailed description: 
      This is a first in human study to evaluate the safety, PK, and PD of RQ-01 when administered
      to adult subjects who have tested positive for SARS-CoV-2 virus, have mild symptom(s) of
      COVID-19 disease, and who are at low risk for developing moderate or severe COVID-19 disease.
      Subjects will be exposed to RQ-01 after nasal administration with the Aptar Bidose nasal
      spray device (BDSI V3). The decrease in SARS-CoV-2 RNA shedding will be measured by reverse
      transcription-quantitative polymerase chain reaction (RT- qPCR) compared with placebo. There
      are currently no Food and Drug Administration (FDA) approved therapies for subjects with mild
      symptoms of COVID who are low risk for progression to moderate-severe disease. Safety of the
      subjects in this study is supported by the safety margin for local adverse events, lack of
      systemic exposure, and availability of antiviral therapies for COVID-19 should subjects'
      disease progress.

      The study may be conducted using traditional outpatient clinic sites or a hybrid model, using
      clinic sites and/or virtual sites, with provisions made to conduct aspects of the study via
      telehealth and/or within subjects' homes. The hybrid model will provide the flexibility
      required to offer the trial in areas with increased incidence of COVID-19 disease, to
      maximize access to trial participation, and to increase diversity of trial subjects.

      Potential study subjects will be identified for screening based on having at least one mild
      symptom consistent with COVID-19 disease. Potential study subjects may additionally present
      with a positive SARS-CoV-2 rapid antigen test (RAT), taken either at-home, or administered at
      a facility (e.g., urgent care testing site). As detailed within the inclusion criteria,
      different entry requirements apply depending on the source and timing of the positive rapid
      antigen test. For all subjects, the time from first positive SARS-CoV-2 rapid antigen test
      result to time of first dose must not exceed 3 days. Also, the first dose of study drug must
      be administered within 4 days of the estimated initial onset of symptoms of COVID-19 disease.

      Subjects who provide written informed consent and meet all eligibility criteria will be
      randomized in a 1:1:1 manner to RQ-01 (high or low dose) or placebo. On the day of
      randomization, all subjects must have at least one mild symptom of COVID-19 disease and a
      positive SARS-CoV-2 RAT result. After the first six subjects are enrolled (2 in each group)
      and have completed all study procedures through Day 7 an early interim safety analysis will
      be performed by the Data Monitoring Committee. Enrollment of new subjects will continue only
      after review by the Data Monitoring Committee and the decision to proceed communicated to the
      investigators.

      Prior to the first dose of study drug, all subjects must be trained by study staff on study
      drug self-administration with the Aptar Bidose nasal spray device, per the instructions
      provided within the Pharmacy Manual and/or subject-facing materials. Subjects will
      self-administer all doses of study drug while observed in-person by the Investigator or
      designee, who must be a trained healthcare professional. Subjects will then be followed for
      an additional 30 days for overall safety including COVID-19 disease symptoms.

      If at any point during the study a subject meets the treatment discontinuation criteria
      outlined within the protocol, including a worsening of COVID-19 disease symptoms, the subject
      will be immediately discontinued from study drug and will continue in follow-up as described
      within the protocol.
    

Intervention name(s): RQ-001; Placebo
Intervention type(s): Combination Product; Other
Intervention description(s): Drug product RQ-001 is the fully assembled device consisting of the vial containing RQ-01 and the actuator. Drug Product RQ-001 has been developed with an Aptar Bidose liquid nasal spray unit device (BDSI V3) capable of intranasally delivering a 200 uL total volume of drug product (specifically, 100 uL per nare, which delivers a 200 uL of total volume). The combination product comprises the drug constituent (RQ-01) and the assembly of commercially available, off-the-shelf device components.
Study staff will be responsible for assembling the drug product RQ-001 and subjects will self-administer under the supervision of study staff in the clinic.; Matching placebo will be manufactured just as RQ-01 drug substance, with the active ingredient addition step omitted. Placebo will appear similar to RQ-01 drug substance as a clear to hazy, colorless to yellowish liquid. Matching placebo will be administered the same way as RQ-01
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: There are 3 different treatment arms that subjects will be randomized in a 1:1:1 ratio. The arms will be evenly distributed with 22 subjects in each arm: 1) low dose of RQ-01; 2) high dose of RQ-01; 3) Placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: First in Human; Phase 1; COVID; Telemedicine