Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation (CDK6COV)

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Drug: Palbociclib

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Brandenburg an der Havel, Germany, 14770
    • Universitätsklinikum Brandenburg an der Havel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palbociclib; 125 mg of palbociclib once daily for 21 consecutive days	Drug: Palbociclib; 125 mg of palbociclib once daily for 21 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of treatment-related treatment discontinuation after 21 days of palbociclib treatment	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to freedom from oxygenation, measured in days after the first treatment dose.	90 days
Time to transfer to ICU	90 days
Course of neutrophil cell count during treatment	21 days
Course of D-dimer during treatment	21 days
Rate of thrombotic events during treatment	21 days
Course of O2 saturation during treatment	21 days
Rate of persisting symptoms after 3, 6, 9 and 12 months	Through completion of safety follow-up up to 12 month
Dose reduction rate	21 days
Rate of (S)AEs at day 21	at day 21

Collaborators and Investigators

• Sponsor: biotx.ai GmbH
• Investigators: Principal Investigator: Mark Reinwald, PD Dr. med., Universitätsklinikum Brandenburg an der Havel

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 12, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; hospitalized; moderate; Palbociclib; CDK4/6 inhibition
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: BXAI-001; 2021-006770-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No