Respiratory Syncytial Virus (RSV) infection MedDRA version: 16.1 Level: HLT Classification code 10038717 Term: Respiratory syncytial viral infections System Organ Class: 100000004862
Conditions
Interventions
Product Code: ALS-008176
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: ALS-008176
Other descriptive name: C12041850-E
Concentration uni
Sponsors
Alios BioPharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 to 45 years, inclusive. 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. 3. A total body weight =50 kg and a BMI of >18. If the BMI is above 30 the subject may be included if the waist measurement is less than 102 cm (male), or less than 88 cm (female). 4. Sexual history: •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 •The following criteria are applicable to partners in a relationship where the partners are of the opposite sex (i.e. the criteria do not apply to those in a same sex relationship): (a)Male subjects must use highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to quarantine, and continuing until 90 days after dosing with IMP. (b)In addition, male subjects must not donate sperm following discharge from quarantine until 90 days after dosing with IMP. (c)Female subjects must: - be post-menopausal females- defined as a history of amenorrhea for at least two years - or have documented status as surgically sterile or post hysterectomy, or, - if of childbearing potential, must have a negative blood pregnancy test at screening and must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to quarantine and continuing until 90 days after dosing with IMP. Acceptable forms of effective contraception include: - Established (i.e. a minimum of 2 weeks prior to admission) use of oral, injected or implanted hormonal methods of contraception. - Placement of an intrauterine device (IUD) or intrauterine system (IUS). - Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. - Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 5. An informed consent document signed and dated by the subject and the Investigator. 6. Sero-suitable for the challenge virus Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 66 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Screening/Day -2 or Day -1 laboratory result outside the reference range . •Hemoglobin and reticulocyte counts = the lower limit of normal for healthy subjects. •a creatinine clearance 1.5 X ULN 2. Use/anticipated use during the study of concomitant medications, including vitamins or herbal and dietary supplements within the specified windows: - Herbal supplements within 7 days before the first study drug dose - Chronically used medications, vitamins or dietary supplements, including any medication known to be an inducer or inhibitor of CYP450 enzymes, within 21 days before the first dose. - Over the counter medications (with the exception of infrequent use of NSAIDs (e.g., ibuprofen) or paracetamol) within 7 days before the first study drug dose (=3 g paracetamol or ibuprofen will be allowed prior to first study drug dose) 3. Subjects who are breastfeeding or who have been pregnant within 12 months prior to the study or who have a positive pregnancy test at any point during screening or prior to inoculation/dosing. 4. Any history or evidence of any clinically significant cardiovascular, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease. a) Eczema/atopic dermatitis except subjects with clinically mild symptoms may be included b) Psoriasis c) Mild or moderate depressive episode(s) which occurred two or more years ago, with good evidence of preceding stressors and which resolved within approximately three months, may be included •Any concurrent serious illness that may interfere with a subject completing the study. 5. Abnormal pulmonary function 6. History or evidence of autoimmune disease or known immunodeficiency of any cause – with the exception of eczema/atopic dermatitis 7. history of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung condition 8. 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 after age 12 years can be included provided the episode is more than four years ago and did not require a hospital admission and/or oral steroids. 9. Positive human immunodeficiency virus, active hepatitis A, B, or C test. 10. Any significant abnormality altering the anatomy of the nose or nasopharynx. 11. Any clinically significant history of epistaxis 12. Any nasal or sinus surgery within six months of inoculation. 13. Recurrent history of fainting. 14. Twelve lead ECG recording with clinically relevant signs of pathology and conduction disturbances. 15. Confirmed positive test for drugs of abuse to be clinically significant. 16. Venous access deemed inadequate for the demands of the study. 17. Any known allergies to the excipients in the challenge virus inoculum. 18. Health care workers who work in units with severely immuno-compromised patients 19. Presence of household member or close contact who: •has known immunodeficiency •is receiving immunosuppressant medication •is undergoing or soon to undergo cancer chemotherapy •has been diagnosed with emphysema, COPD, or other severe lung disease •has received a bone marrow or solid organ transplant •resides in a nursing home. 20. •Evidence of vaccinations within the four weeks prior to inoculation/dosing. •Intention to receive any vaccination(s) before the Day 28 Follow Up V
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antiviral effect of oral ALS-008176 compared to placebo after inoculation with RSV-A Memphis 37b virus.;Secondary Objective: To evaluate ALS-008176 compared to placebo in healthy volunteers inoculated with RSV in terms of: •Safety and tolerability •PK profile of ALS-008176 and its metabolites (e.g., ALS-008112, and ALS-008144) •Relationship between the PK and PD of ALS-008176 (and its metabolites) •Effect of on clinical symptoms of RSV infection •Development of viral resistance to ALS-008176 ;Primary end point(s): Reduction in AUC0-t of RSV-A Memphis 37b viral load as determined by quantitative PCR assay of nasopharyngeal wash.;Timepoint(s) of evaluation of this end point: Day 2-12 and follow up visit 1 & 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety data including, but not limited to, tabulation of adverse events (AEs), physical examinations, spirometry, vital signs, 12-lead ECGs and clinical laboratory results (including chemistry, haematology, and urine). 2. PK parameters of ALS-008176, ALS-008112 and ALS-008144 (and other metabolites as applicable) in plasma following repeat dose administration: Cmax, Cmin, Tmax, t1/2, CL/F and Vdss/F (excluding metabolites), AUC0-12h, AUC12-24h AUC0-24h, and AUC0-last 3. Reduction in total weight of mucus produced post viral inoculation, through last administration of IMP. 4. Relationship between various PK parameters (e.g., Cmax, Cmin, and AUC) and antiviral endpoints (e.g., viral load AUC, duration of shedding, symptom scores). 5. Change in total RSV-A symptoms after challenge until treatment cessation (using a composite of 10 self-reported symptoms on the symptom diary card). 6. Sequence analysis of the RSV polymerase region (amino acids 550-1100) of the RSV L protein.;Timepoint(s) of evaluation of this end point: 1. Days 1-12 & follow up visit 1 & 2 2. Day 12 3. Days 1-12 4. PK parameters Day 12 & antiviral endpoints Day 2-12 & follow up visit 1 & 2 5. Day 1-12 & follow up visit 1 6. pre-dose, all 5 dosing days and thereafter until virus is no longer detectable | — |
Countries
United Kingdom
Contacts
Public ContactJohn Fry
Alios BioPharma
Outcome results
None listed