A Study to Examine the Duration of Effect of PrEP-001 in Healthy Subjects Challenged With HRV-16
Condition: Viral Upper Respiratory Tract Infection
MeSH terms: Respiratory Tract Infections
Intervention: PrEP-001; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blind
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Rhinovirus; Healthy volunteer; Outpatient; Cold virus; HRV-16

Summary:

      A study to examine the duration of effect of PrEP-001 in healthy subjects challenged with
      HRV-16
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged 18 to 55 years on the day of first dosing with Investigational Medicinal Product
             (IMP).

          2. In good health with no history of major medical conditions from the medical history,
             physical examination, and routine laboratory tests as determined by the Investigator
             at a screening evaluation. A subject with a history of Herpes type 1 or 2 infection
             may be included if there are no active lesions present and the subject is not taking
             active medication.

          3. A total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m2. If the BMI is more
             than 30 kg/m2, the subject may be included if the waist measurement is less than 102
             cm (male), or less than 88 cm (female).

          4. The following inclusion criteria are applicable to subjects who are in a heterosexual
             relationship and female subjects in a female same sex relationship (i.e. the criteria
             do not apply to those in a male same sex relationship):

               1. True abstinence - when this is in line with the preferred and usual lifestyle of
                  the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods] and withdrawal are not acceptable methods of
                  contraception).

                  Or

               2. Two forms of effective contraceptive methods among (between) the couple, which
                  are defined as:

                  • For males: i. Condom with spermicidal foam/gel/film/cream, sterilisation (with
                  the appropriate post-vasectomy documentation of the absence of sperm in the
                  ejaculate. This applies only to males participating in the study).

                  • For females: i. Women no longer of child bearing potential (post-menopausal
                  females are defined as having a history of amenorrhea for at least 2 years,
                  otherwise they should have documented status as being surgically sterile or post
                  hysterectomy. The latter applies only to female subjects participating in the
                  study).

                  ii. If of childbearing potential, then acceptable forms of contraception include:

                  o Established (a minimum of 2 weeks prior to first dosing with IMP) use of oral,
                  injected or implanted hormonal methods of contraception.

                    -  Placement of an intrauterine device (IUD) or intrauterine system (IUS).

                    -  Barrier methods of contraception or occlusive cap (diaphragm or
                       cervical/vault caps), both with one of the following - spermicidal
                       foam/gel/film/cream/suppository.

                       • The longevity of contraception is as follows: i. Male subjects must comply
                       with agreed contraception from the first IMP dosing, and continuing until 90
                       days after the date of the last IMP dosing or Viral Challenge which ever
                       happens later.

                  ii. Male subjects must not donate sperm following the first IMP dosing, and
                  continuing until 90 days after the date of the last IMP dosing or Viral Challenge
                  which ever happens later.

                  iii. Female subjects of childbearing potential must have a negative pregnancy
                  test at screening and just prior to the date of first dosing with IMP and must be
                  using contraception consisting of two forms of birth control (one of which must
                  be a barrier method) starting from at least 14 days prior to the first IMP dosing
                  and continuing until 90 days after the date of the last IMP dosing or Viral
                  Challenge whichever happens later.

          5. An informed consent document signed and dated by the subject and the Investigator.

          6. Sero-suitable for the Challenge Virus.

          7. Subjects must be willing to comply with the protocol visit schedule including both
             face to face and phone visits.

        Exclusion Criteria:

          1. Subjects who have a significant history of any tobacco use at any time (total ≥10 pack
             year history [10 pack years is equivalent to one pack of 20 cigarettes a day for 10
             years]).

          2. Females who:

               -  Are breastfeeding, or

               -  Have been pregnant within 6 months prior to the study, or

               -  Have a positive pregnancy test at any point during screening or prior to first
                  dosing with IMP

          3. Any history or evidence of any clinically significant cardiovascular, dermatological
             (including psoriasis), gastrointestinal, endocrinological, haematological, hepatic,
             immunological, metabolic, urological, neurological, renal, and/or other major disease
             that, in the opinion of the Investigator, may interfere with a subject completing the
             study. The following conditions apply:

               -  Subjects with clinically mild atopic eczema/atopic dermatitis may be included at
                  the Investigator's discretion (e.g., if there is no regular use of topical
                  steroids, no eczema in cubital fossa)

               -  Subjects with any history of significant psychiatric illness should be excluded
                  unless the illness resolved within 3 months, Subjects with a diagnosis of mild or
                  moderate depressive episode(s) which occurred 2 or more years ago, with good
                  evidence of preceding stressors and which resolved within approximately 3 months
                  may be included in the Investigator's opinion

               -  During screening, if subjects have a total cholesterol level > 6mmol/l they will
                  be excluded from the study.

               -  Any concurrent serious illness (e.g., COPD, history of malignancy) that may
                  interfere with a subject completing the study. Basal cell carcinoma within 5
                  years of initial diagnosis or with evidence of recurrence is also an exclusion

          4. Abnormal pulmonary function in the opinion of the Investigator as evidenced by the
             responses to the respiratory screening questions and/or clinically significant
             abnormalities in spirometry (forced expiratory volume in 1 second (FEV1) and forced
             vital capacity (FVC)).

          5. History or evidence of autoimmune disease or known immunodeficiency of any cause -
             with the exception of atopic eczema/atopic dermatitis as described in exclusion
             criterion number (3).

          6. Subjects with any history of COPD, pulmonary hypertension, asthma or chronic lung
             condition of any aetiology.

             A history of childhood asthma before the age of 12 years is acceptable provided the
             subject is asymptomatic without treatment. Subjects with a single episode of wheezing
             (lasting less than 8 weeks) after age 12 years can be included at the Investigator's
             discretion provided the episode was more than 4 years ago and did not require a
             hospital admission and/or oral/intravenous steroids.

          7. Positive HIV, active hepatitis A (HAV), B (HBV), or C (HCV) test.

          8. Any significant abnormality altering the anatomy of the nose or nasopharynx.

          9. Any clinically significant history of epistaxis (nosebleeds) within the last 12 months
             and/or a history of being hospitalized due to epistaxis on any previous occasion.

         10. Any nasal or sinus surgery within 6 months of first dosing (due to intranasal IMP).

         11. Recurrent history of fainting.

         12. Twelve-lead ECG recording with clinically relevant signs of pathology and conduction
             disturbances as judged by the Investigator.

         13. Confirmed positive test for drugs of abuse or cotinine deemed by the Investigator to
             be clinically significant.

         14. Venous access deemed inadequate for the phlebotomy and cannulation demands of the
             study.

         15. Any clinically significant allergies such as allergy to the excipients in the
             Challenge Virus inoculum as stipulated in the protocol.

         16. Evidence of vaccinations within the 4 weeks prior to the planned date of first dosing
             with IMP or an intention to receive any vaccination(s) before the last day of the
             study.

         17. Those employed, or immediate relatives of those employed, at hVIVO or the Sponsor.

         18. Receipt of blood or blood products, or loss (including blood donations) of 450 mL or
             more of blood during the 3 months prior to the planned date of first dosing with IMP
             (whichever occurs first) or planned during the 3 months after the final visit.

         19. Use within 7 days prior to the planned date of first dosing with IMP of any medication
             or product (prescription or over-the-counter), for symptoms of hay fever, rhinitis,
             nasal congestion or respiratory tract infections including the use of nasal steroids.

         20. Receipt of any investigational drug within 3 months prior to the planned date of first
             dosing with IMP or receipt of three or more investigational drugs within the previous
             12 months prior to the planned date of first dosing with IMP.

             Prior inoculation with a virus from the same virus-family as the Challenge Virus or
             prior participation in another Human Viral Challenge study with a respiratory virus in
             the preceding 12 months taken from the date of first dosing with IMP in the previous
             study to the date of expected first dosing in this study.

         21. Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral
             drugs within 6 months prior to the planned date of first dosing with IMP. History of
             chemotherapy of therapy with immunomodulators.

         22. History suggestive of respiratory infection within 14 days prior to first dosing or
             presence of significant respiratory symptoms on the day of first dosing with IMP

         23. Use or anticipated use during the conduct of the study of concomitant medications
             (prescription and/or non-prescription), including vitamins or herbal and dietary
             supplements within the specified windows, unless in the opinion of the Investigator
             and/or Sponsor's Medical Expert, the medication will not interfere with the study
             procedures or compromise subject safety. Specifically, the following are excluded:

               -  Herbal supplements within 7 days prior to the planned date of first dosing with
                  IMP

               -  Chronically used medications, vitamins or dietary supplements, including any
                  medication known to be an inducer or inhibitor of cytochrome P450 (CYP450)
                  enzymes, within 21 days prior to the planned date of dosing with IMP

               -  Over the counter medications (e.g., paracetamol or ibuprofen) where the dose
                  taken over the preceding 7 days prior to the planned date of first dosing with
                  IMP has exceeded the maximum permissible 24-hour dose (e.g., ≥4 g paracetamol
                  over the preceding week)

         24. Any other finding that, in the opinion of the Investigator, deems the subject
             unsuitable for the study.