JPWO2021159027A5 - - Google Patents

Description

In certain embodiments, the treatment period (e.g., the first treatment period, the second treatment period and/or the third treatment period) is for a period of at least 1 week, such as at least 2 weeks, 3 weeks, 4 weeks or more. be. In certain embodiments, the treatment period (e.g., first treatment period, second treatment period, and/or third treatment period) is at least 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks. weeks, 28 weeks, 32 weeks, 36 weeks, 40 weeks, 44 weeks, 48 weeks or more . In certain embodiments, the treatment period is for a period of at least 8 weeks. In certain embodiments, the treatment period is up to about 4 weeks, or up to about 6 weeks, 8 weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks, 24 weeks, 28 weeks, 32 weeks, 36 weeks, 40 weeks, A period of 44 or 48 weeks. In certain embodiments, the treatment period is up to about 8 weeks. In certain embodiments, the treatment period is up to about 12 weeks.

Claims (48)

A medicament for the treatment of coronavirus infection comprising pegylated interferon lambda-1a , comprising: administering to a subject a therapeutically effective amount ;
Until a sustained reduction in the viral load of the coronavirus is achieved.
until reduction of coronavirus RNA to undetectable levels is achieved.
A drug that is administered subcutaneously until a reduction in viral shedding rate or amount is achieved or until an improvement in the subject's symptoms is achieved. The medicament of claim 1, wherein the medicament is administered for at least 1 week, 2 weeks, 3 weeks, 4 weeks, 1 to 12 weeks, 2 to 12 weeks, or 3 weeks to 24 weeks. Pegylated interferon lambda-1a 180 micrograms once weekly, 90 micrograms twice weekly, 80 micrograms twice weekly , 180 micrograms/week , 120 micrograms once weekly, 60 micrograms weekly 3. Medication according to claim 1 or 2, administered at a dose of 70 micrograms twice a week or 120 micrograms per week . ( i) 160-180 micrograms pegylated interferon lambda-1a/week for the first treatment period, then 150-170 micrograms/week for the second treatment period; or (ii) 180 micrograms/week for the first treatment period. , then 170-120 micrograms/week for the second treatment period, (iii) 120 micrograms/week for the first treatment period, then 80 micrograms/week for the second treatment period, or (iv) the first treatment period. of (i) and (ii) ; 3. Medicament according to claim 1 or 2, wherein the doses administered for each may be divided and administered more than once a week. 5. The medicament of claim 4 , wherein the first treatment period is longer than the second treatment period, or the second treatment period is longer than the first treatment period, or the first and second treatment periods are of the same duration. 5. The medicament of claim 4 , wherein the first treatment period is for a period of at least 1 week, at least 2 weeks, at least 6 weeks or at least 8 weeks. 2. The medicament of claim 1, wherein the treatment results in a reduction of the viral load of the coronavirus in the subject by at least 2.0 log ₁₀ coronavirus RNAIU/mL serum. 2. The medicament of claim 1, wherein the treatment results in an amelioration of the subject's symptoms. 2. The medicament of claim 1, wherein the improvement in the subject's symptoms includes a reduction in fever, a reduction in fatigue, a reduction in cough, a reduction or absence of shortness of breath, a reduction in sensations of tingling and pain, and a reduction or absence of diarrhea. 3. The medicament of claim 1, wherein the treatment results in a viral load of the coronavirus that is below the level of detection. 2. The medicament of claim 1 , co-administered with an antiviral . 12. The medicament of claim 11 , wherein the antiviral comprises one or more of remdesivir, chloroquine, tenofovir, entecavir, protease inhibitors (lopinavir/ritonavir). 2. The medicament of claim 1, wherein, prior to treatment, the subject has a baseline viral load of ^{up to 104} coronavirus RNA copies/mL sample. 2. The medicament of claim 1, wherein upon administration a sustained virological response (DVR) is observed in the subject. 2. The medicament of claim 1, wherein the subject has one or more of the following symptoms of pneumonia, fever, cough, shortness of breath, and myalgia. The medicament of claim 1, wherein the coronavirus is a zoonotic virus. The drug according to claim 1, which is administered at the beginning of coronavirus infection to shorten the duration of coronavirus infection and prevent the development of respiratory complications. The initial stage of coronavirus infection is 1 to 10 days after the initial viral load determination and before the subject experiences respiratory symptoms requiring hospitalization; the period during which the subject experiences mild to moderate respiratory symptoms; 18. The medicament of claim 17 , comprising one or more of a period of symptoms; or a period of mild symptoms of a respiratory infection in which the subject is not in respiratory distress. Mild symptoms of respiratory infection without respiratory distress include body temperature <39.0°C, respiratory rate <25, O ₂ % saturation >95% or P/F ratio >150 on room air or supplemental oxygen via nasal cannula. 19. The medicament of claim 18 , comprising: Subject had the following platelet count <90,000 cells/ ^mm3 ; white blood cell (WBC) count <3,000 cells/ ^mm3 ; absolute neutrophil count (ANC) <1,500 cells/mm3 in the 12 months prior to administration. ³ ; hemoglobin <11 g/dL in women and <12 g/dL in men; estimated creatinine clearance (CrCl) by Cockcroft-Gault formula <50 mL/min; ALT and/or ALT levels >10 times the upper limit of normal; bilirubin levels other than those due to Gilbert syndrome. ≥2.5 mg/dL; serum albumin level <3.5 g/dL; or one or more laboratory abnormalities of international normalized ratio (INR) ≥1.5 (unless the patient is continuing anticoagulation) 2. The medicament of claim 1, which does not exhibit. The medicament of claim 1, wherein the viral shedding rate or amount is determined by RT-PCR negativity or measurement of reduced amount of virus. 2. The medicament of claim 1, wherein the improvement in symptoms is determined by a clinical improvement in _O2 status. Subjects have mild symptoms and are not hospitalized; subjects have mild to moderate symptoms and are not hospitalized; subjects have mild to moderate symptoms and are hospitalized; subjects have mild to moderate symptoms and are hospitalized and require supportive _O2 or an asymptomatic exposed subject . RT-PCR was used to test viral load on days 7 and 14 of treatment, and subjects had a similar disease state at the start of treatment and received only standard supportive care on days 7 and 14. 2. The medicament of claim 1, which has a low viral load in the eye. 2. The medicament of claim 1, wherein the subject is mildly to moderately ill and the subject exhibits a decrease in viral shedding rate or amount. Oxygen status (ordinal scale) if the subject is a hospitalized subject with mild to moderate illness requiring supportive _O 2. The medicament of claim 1, which exhibits clinical improvement in ). 27. The medicament of claim 26 , wherein the medicament is administered to the subject twice, one week apart. The subject has mild to moderate disease, is not hospitalized or has been hospitalized, and is receiving pegylated interferon lambda-1a at a twice-weekly dose of 120 mcg or 180 mcg, and the subject is on treatment day 7 and 2. The agent of claim 1, which exhibits a low viral shedding rate as measured by RT-PCR negativity on day 14. An agent for preventing or reducing the incidence of SARS-CoV-2 infection in a subject , comprising interferon lambda , administered by subcutaneous injection at weekly or biweekly doses of 1 20 mcg or 180 mcg. and the subject is RT-PCR negative 14 days after the first dose of interferon lambda. 30. The medicament of claim 29 , wherein the subject has lower RT-PCR levels of SARS-CoV-2 than subjects receiving standard supportive care. an agent for preventing or reducing the incidence of SARS-CoV-2 infection in subjects exposed to SARS-CoV-2 , comprising interferon lambda , wherein a dose of 180 mcg interferon lambda is administered by subcutaneous injection; and the subject is in a similar disease state at the start of treatment 7 days after injection and has a lower viral load than a subject receiving standard supportive care . 32. The drug of claim 31 , wherein the subject is in a similar disease state at the start of treatment and has a lower rate of infection than a patient who does not receive interferon lambda. 33. The medicament of claim 31 or 32 , wherein the subject has been exposed to SARS-CoV-2 but infection has not been confirmed. A medicament comprising interferon lambda for the treatment of a subject having a SARS-CoV-2 infection or being exposed to SARS-CoV-2, wherein a therapeutically effective dose of interferon lambda is administered. . 35. The medicament of claim 34 , which is administered subcutaneously . 36. The medicament of claim 34 or 35 , wherein the interferon lambda is interferon lambda-1a. 35. The medicament of claim 34 , wherein the interferon lambda is pegylated interferon lambda. 35. The medicament of claim 34 , wherein the rate of hospitalizations includes emergency room admissions. 2. The agent of claim 1, wherein the subject has a viral load of 6 log ₁₀ copies/mL or more or 6 log ₁₀ IU/mL to 11 log ₁₀ IU/mL . A drug for treating coronavirus infection , including interferon lambda , administered subcutaneously to a subject at a dose of 120 mcg to 180 mcg, and the subject has 10 ⁶ SARS-CoV-2 RNA copies/mL or more or Drugs with a viral load greater than or equal to 6 log ₁₀ IU/mL. A dose of 120 mcg or 180 mcg of interferon lambda is administered and the subject exhibits a decrease in viral shedding as measured by a negative viral load on days 7, 14 and/or 28 of treatment compared to the start of treatment. , the medicament of claim 40 . 42. The agent of claim 40 or claim 41 , wherein the subject has a viral load of 6 log ₁₀ IU/mL to 1 log ₁₀ IU/mL. 41. The agent of claim 1 or claim 40 , wherein the time to cessation of elimination is faster in seropositive subjects than in seronegative subjects at baseline. 41. The medicament of claim 40 , wherein the subject has a greater reduction in SARS-CoV-2 RNA viral load reduction from baseline at day 5 of treatment compared to a control. 42. The agent of claim 41 , wherein the subject is 4.1 times or 95% more likely to be cleared of virus by day 7 of treatment compared to controls. 42. The medicament of claim 41 , wherein the subject has a viral load of 6 log ₁₀ IU/mL or greater and the subject is negative for virus by day 7 of treatment. 42. The medicament of claim 41 , wherein the subject clears the virus by day 7 of treatment. 42. The medicament of claim 41 , wherein the interferon lambda is pegylated interferon lambda-1a.