Clinical trial NCT05371275: Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation
Official title: Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
moderate
hospitalized
Palbociclib
CDK4/6 inhibition
Lead sponsor: biotx.ai GmbH
Sponsor class: INDUSTRY
First posted: 2022-05-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a one-site, interventional, prospective, single-arm, open-label, controlled phase-IIa trial evaluating the safety and efficacy of palbociclib in hospitalized, moderate COVID- 19 cases.

Detailed description: The study will include hospitalized, moderate COVID-19 cases that have a risk of respiratory failure.

The study will generally consist of:

* A short screening phase (1 day) before enrollment and thus treatment decision.
* A 21 day treatment phase with one "cycle" of palbociclib
* An up to day 90 Safety Follow-Up Phase

The first three patients will be enrolled and treated one by one; the independent safety data review committee (ISRC) will review each patient after D21 before enrollment of the subsequent patient is permitted.

Eligibility criteria: Inclusion Criteria:

1. age \>= 18 years
2. positive PCR COVID-19 test (max. 72h old)
3. known vaccination status
4. ANC \>= 1,000/mm3 and platelets \>= 50,000/mm3
5. willingness to participate (written informed consent)
6. established risk factors for a severe course of COVID-19-disease, for example: adipositas, cardiovascular disease including arterial hypertension, advanced age \> 60, chronic lung disease including asthma, diabetis type I or II, chronic kidney disease, chronic liver disease
7. Oxygen supply: ≤ 2 liters/minute
8. Women of childbearing potential (WOCBP): must have a negative pregnancy test (ß- HCG urine or serum test) a. WOCBP is considered as i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile.

   b. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

   c. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
9. Use of highly effective contraception method

   1. All potentially fertile participants, or their male partners, must use an adequate, medically approved method of contraception or agree to abstinence during and at least 3 weeks (females) and 14 weeks (males) after treatment with Palbociclib.
   2. For females, highly effective birth control should be used, i.e., combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, or intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner. As there is no information available on the interaction of palbociclib with oral contraceptives, a double-barrier contraception is necessary in this case.
   3. Males must agree to use a condom for at least 14 weeks after the treatment phase.

Exclusion Criteria:

1. age \< 18 year
2. ECOG \>= 3
3. ANC \< 1,000/mm3 and platelets \< 50,000/mm3
4. intensive care patient
5. treatment with any other CDK4/6 Inhibitor
6. pregnant or breast-feeding women
7. patients receiving immunosuppressants for other diseases (e.g. rheumatoid arthritis)
8. known malignancy in the past 5 years other than basal cell carcinoma
9. baseline O2-Saturation \< 92%
10. participation in any other medical device or medicinal product study within the previous month

Primary outcomes:
measure: Rate of treatment-related treatment discontinuation after 21 days of palbociclib treatment
timeFrame: 21 days
Secondary outcomes:
measure: Time to freedom from oxygenation, measured in days after the first treatment dose.
timeFrame: 90 days
measure: Time to transfer to ICU
timeFrame: 90 days
measure: Course of neutrophil cell count during treatment
timeFrame: 21 days
measure: Course of D-dimer during treatment
timeFrame: 21 days
measure: Rate of thrombotic events during treatment
timeFrame: 21 days
measure: Course of O2 saturation during treatment
timeFrame: 21 days
measure: Rate of persisting symptoms after 3, 6, 9 and 12 months
timeFrame: Through completion of safety follow-up up to 12 month
measure: Dose reduction rate
timeFrame: 21 days
measure: Rate of (S)AEs at day 21
timeFrame: at day 21
Other outcomes:
Locations:
city: Brandenburg an der Havel
country: Germany
facility: Universitätsklinikum Brandenburg an der Havel
Study officials:
affiliation: Universitätsklinikum Brandenburg an der Havel
name: Mark Reinwald, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: