Phase 2B Study on Safety and Therapeutic Efficacy of DAS181 in Adult Subjects With Naturally Acquired Influenza
Phase 2B Study on Safety and Therapeutic Efficacy of DAS181 in Adult Subjects With Naturally Acquired Influenza
This protocol will seek to enroll 372 adult otherwise healthy subjects presenting with
 influenza-like illness (ILI). Subjects will enter the study based on listed
 inclusion/exclusion criteria, including a positive Rapid Antigen Test (RAT) for influenza
 virus (IFV).

 Subjects will be randomized into one of three treatment groups: a DAS181 30 mg total dose
 group (DAS181-F02 formulation), a DAS181 60 mg total dose group (DAS181-F04 formulation) or a
 placebo group.

 The modified intent to treat (mITT) analysis set will include subjects with confirmed
 influenza as documented by qPCR or TCID50. The full analysis set will be used for activity
 analysis and will include all randomized subjects with baseline and treatment data. Per
 protocol, the safety analysis sets are described below in statistical methods.

 A subpopulation of 60 participants will also have additional PK and Immunogenicity blood
 samples collected. For this subgroup, PK and Immunogenicity samples will be collected at all
 study visits.
Inclusion Criteria:

 1. Male and female subjects in generally good health in the opinion of the investigator
 as determined by vital signs, medical history, and a physical exam based on medical
 history.

 2. Subjects must be able to verbalize understanding of the consent form, provide written
 informed consent and verbalize willingness to complete study procedures.

 3. Be 18 to 70 years of age (inclusive).

 4. Subjects must weigh at least 50 kg and must have a Body Mass Index (BMI) of no greater
 than 40.00.

 5. Febrile, oral temperature ≥100.4°F (≥38.0°C) in combination with symptoms

 6. At least one respiratory symptom:

 -  Cough

 -  Sore throat

 -  Wheezing

 -  Sneezing

 -  Shortness of breath

 -  Nasal congestion

 -  Earache

 -  Pleuritic chest pain

 7. At least one constitutional symptom:

 -  Headache

 -  Myalgia (body aches and pains)

 -  Fever or feverish (sweat/chills)

 -  Prostration (fatigue, tired, lacking energy)

 8. Positive rapid antigen test (RAT) for influenza performed using FDA-cleared and
 CLIA-waived commercially available rapid antigen test supplied by the sponsor.

 9. Blood pressure within normal limits (systolic 90-150 mmHg; diastolic 50-95 mmHg) and
 heart rate between 45 and 140 beats per minute.

 10. Onset of symptoms no more than 48 hours prior to diagnosis.

 Note: Time of onset of illness is defined as either:

 1. the time when the temperature was first measured as elevated (38 C) OR

 2. the time when the subject experienced the presence of at least one symptom, whichever
 occurs first 11. Female subjects must be post-menopausal (one year or greater without
 menses), surgically incapable of childbearing, or practicing two effective methods of
 birth control. Acceptable methods may include intrauterine device, spermicide, barrier
 and hormonal contraception. A female subject must agree to practice an acceptable
 method of birth control during the study period. All female subjects regardless of
 menopausal status or surgical history must have had a negative urine pregnancy test
 during the screening visit and prior to dosing.

 12. Male subjects must agree to use medically accepted form of contraception during the
 study period.

 Exclusion Criteria:

 1. Have received any investigational drug or investigational vaccine within 8 weeks prior
 to study drug dosing.

 2. Have had a serious adverse reaction or previous episode of anaphylaxis related to any
 drug.

 3. Have received blood products within 6 months of study enrollment.

 4. Have concurrent cystic fibrosis or emphysema.

 5. Have sickle cell disease.

 6. Known IGE mediated allergic response to lactose (not lactose intolerance).

 7. Any history of congenital or acquired bleeding abnormalities.

 8. Existence of any surgical, medical, or laboratory condition that, in the judgment of
 the clinical investigator, might interfere with the safety, distribution, metabolism
 or excretion of the drug.

 9. Use of antiviral influenza medications within 10 days prior to screening (Subjects
 will be prohibited from taking antiviral influenza medications during the course of
 the trial).

 10. Current clinical evidence of a recognized or suspected uncontrolled non-influenza
 infectious illness with onset prior to screening.

 11. Known hypersensitivity to DAS181.

 12. Women who are pregnant (urine pregnancy test), who are attempting to become pregnant,
 or who are breast-feeding.

 13. Uncontrolled seizure disorder or history of seizure activity within 12 months prior to
 study participation.

 14. Any significant findings in the subject's medical history or physical examination
 that, in the opinion of the investigator, would affect subject safety or compliance
 with the dosing schedule.

 15. Subjects with history of asthma or chronic obstructive pulmonary disease (COPD)
 requiring the use of acute or chronic medication in the past 3 years.

 16. Subjects with acute diagnosis of a chronic medical condition within the last 3 months.

 17. Subjects with a chronic medical condition that have initiated or changed dosing or
 regimen of prescription medications to treat the chronic medical condition within the
 last 3 months. (Any changes in chronic medications during the 28 day enrollment period
 will be captured in the source documentation under concomitant medications).

 18. Subjects with current or previous history of the following: systemic disorders,
 immunological disorders, hepatitis B virus (HBV), hepatitis C virus (HCV) or
 cirrhosis, transplant recipients, or other immunosuppressive illness.

 19. Subjects with cancer or history of hematologic malignancy. Cancer is defined as any
 active neoplastic diseases excluding noninvasive basal cell carcinoma.

 20. Subjects who have had or are scheduled to have surgery within 30 days of initiation of
 the study.

 21. Subjects who have donated or lost more than 500 mL of blood in the two months prior to
 screening.

 22. Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion
 of the principal investigator, would affect subject safety and/or compliance.

 23. Family members of site staff directly involved in study conduct are excluded from
 study participation.

 24. Subjects with an oxygen saturation (Sa02) level of <92% as measured by pulse oximeter.

 25. Subjects with a modified CURB-65 score of 2 or higher.