Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection (COVID-19)
Condition: COVID-19
MeSH terms: COVID-19; Pneumonia; Coronavirus Infections
Intervention: Duvelisib; Placebo
Intervention description: Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.; A placebo to match duvelisib will be taken orally twice per day for 14 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SARS-CoV-2

Summary:

      In this study, patients with severe coronavirus disease 2019 (COVID-19) infection will be
      randomized to receive duvelisib or a placebo. Participants will be enrolled at Emory
      University Hospital and will be identified and recruited by their treating physician and
      research team.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Hospitalized in participating facility.

          -  Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g.,
             chest x-ray or CT scan).

          -  Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction
             (PCR) or other authorized or approved assay in any specimen collected within 72 hours
             prior to enrollment. Note - An exception must be requested to the Sponsor if ≥72 hours
             since positive test.

          -  Symptoms suggestive of severe systemic illness with COVID-19, such as respiratory rate
             > 30 breaths per minute, heart rate >125 beats per minute, oxygen saturation (O2 sat)
             in the blood of <93% on room air at sea level or the ratio of arterial oxygen partial
             pressure to fractional inspired oxygen (PaO2/FiO2)< 300

          -  18 years of age or older

          -  Patients with hematological parameters at screening consistent with < grade 2 NCI
             CTCAE v5.0 toxicity: hemoglobin >8 g/dL, platelet count >50,000 K/mcl, an absolute
             neutrophil count (ANC) >1,000/mm3, and an absolute lymphocyte count (ALC) >500/mm3.

          -  Patients with laboratory measurements of liver function at screening consistent with <
             grade 2 NCI CTCAE v5.0 toxicity: alanine aminotransferase (ALT) < 5 times the upper
             limit of normal (ULN); aspartate aminotransferase (AST) < 5 times ULN; and bilirubin <
             3 times ULN.

          -  The effects of duvelisib on the developing human fetus are unknown. For this reason,
             women of child-bearing potential (WOCBP) must have a negative serum or urine
             pr5egnancy test prior to starting therapy. WOCBP and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) from
             enrollment into this study until at least 60 days after the first dose of duvelisib. A
             woman of childbearing potential (WOCBP) is a sexually mature woman who: 1) has not
             undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in
             the preceding 24 consecutive months. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 2 months after completion of duvelisib administration. WOCBP must
             have a negative pregnancy test within 24 hours of the first dose of duvelisib.

          -  The patient must be willing to comply with fertility requirements as below:

               -  Total abstinence (when this is in line with the usual practice and lifestyle of
                  the patient) will be accepted. Periodic abstinence (i.e., calendar, ovulation,
                  post-ovulation methods) and withdrawals are not acceptable forms

               -  If a female participant is of reproductive potential, the participant (and her
                  partner) must agree to use of one of the following combinations of birth control
                  during the study and for 2 months after the last dose of study drug (or tubal
                  ligation as a single method):

                    -  Use of a double-barrier method of contraception: condoms (male or female)
                       and a diaphragm or cervical cap with spermicide;

                    -  Use of an IUD and a barrier method: condoms (male or female, with or without
                       spermicide) or a diaphragm or cervical cap with spermicide;

                    -  Tubal ligation.

               -  Women who are post-menopausal, defined as age greater than 45 and no menses for
                  at least 24 consecutive months, or who have had a hysterectomy, are considered
                  not of reproductive potential.

               -  Males must agree to using contraception during the study and for 2 months after
                  the last dose of study drug or have undergone a male sterilization procedure (at
                  least 6 months prior to screening.

               -  Use of oral (estrogen and progesterone), injected or implanted hormonal methods
                  of contraception, or placement of an intrauterine device (IUD) or intrauterine
                  system (IUS) or other forms of contraception that comparable efficacy (failure
                  rate <1%). In case of oral contraception, the woman should be stable on the same
                  pill for a minimum of 3 months prior to enrollment on the study.

          -  Patients must agree not to donate blood, sperm/ova or any other organs while taking
             protocol therapy and for at least 2 weeks after stopping treatment.

          -  Willingness and ability of the patient to comply with scheduled visits, drug
             administration plan, protocol specified laboratory tests, other study procedures and
             study restrictions

          -  Evidence of personally signed informed consent indicating that the subject is aware of
             the life-threatening nature of the disease and has been informed on the procedures to
             be followed, the experimental nature of the therapy, alternative, potential risks and
             discomforts, potential benefits and other pertinent aspects of study participation.

        Exclusion Criteria:

          -  Patients requiring mechanical ventilation (intubation or Bi-PAP) at the time
             randomization.

          -  Patients receiving any investigational drugs other than drugs or therapies to treat
             COVID-19, with the exception of investigational immune-modulatory drugs as per section
             5.4.

          -  Pregnant women are excluded from this study because duvelisib is agent with the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with duvelisib, breastfeeding should be discontinued before starting study drug
             and breastfeeding should not be resumed until at least 1 month after last dose of
             study drug.

          -  Clinical suspicion that the etiology of acute illness (acute decompensation) is
             primarily due to a condition other than COVID-19

          -  Known contraindication to duvelisib

          -  Patients with hepatic cirrhosis as defined by symptomatic liver dysfunction; liver
             fibrosis by biopsy; ALT > 5 times ULN, AST> 5 times ULN, or bilirubin > 3 times ULN.

          -  Patients with autoimmune diseases or patients on chronic immunosuppressive medications
             at the time of hospital admission or screening.