A Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults With Complex Lymphatic Malformations

NCT ID: NCT04994002

Last Updated: 2022-03-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-03
• Study Completion Date: 2022-06-30

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of CERC-006 in adults (aged 18-31 years) with active, moderate to severe complex lymphatic malformations.

Conditions

Lymphatic Malformation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: CERC-006 (0.5 mg)

Approximately 5 participants will receive CERC-006 at a dose of 0.5 mg twice daily for 28 days.

Group Type: EXPERIMENTAL

CERC-006

Intervention Type: DRUG

Oral solution

Cohort 2: CERC-006 (1 mg)

Following a safety review, if there are no clinically important safety findings in Cohort 1, a second cohort of approximately 5 participants will be enrolled to receive CERC-006 at a dose of 1 mg twice daily for 28 days.

Group Type: EXPERIMENTAL

CERC-006

Intervention Type: DRUG

Oral solution

Interventions

CERC-006

Oral solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants must fulfill the following requirements to be eligible for the study:

1. Participant is 18 to 31 years of age (inclusive) at the time of consent.

2. Participant has a verified diagnosis of a complex lymphatic malformation. Other moderate to severe vascular anomalies with associated lymphatic involvement will be considered, with approval by the study medical monitor.

3. Participant's complex lymphatic malformation is considered, in the opinion of the investigator, to be moderate to severe.

4. Participant has adequate liver function defined as:

• Total bilirubin (sum of conjugated and unconjugated) ≤1.5 × upper limit of normal (ULN)
• Aspartate transaminase/Alanine aminotransferase (AST/ALT) <5 × ULN
• Serum albumin > 2 g/dL

5. Participant has fasting low-density lipoprotein (LDL) of <160 mg/dL.

6. Participant has adequate bone marrow function defined as:

• Peripheral absolute neutrophil count (ANC) > 1000/µL
• Hemoglobin > 8.0 g/dL
• Platelet count ≥ 50,000/µL

7. Participant has adequate renal function defined as:

• Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance of > 50 mL/min according to the Cockcroft-Gault equation

8. Participant has agreed to and met the washout period as follows:

• At least 14 days prior to initiation of CERC-006 if receiving sirolimus (also known as rapamycin), mitogen-activated protein kinase (MEK) inhibitors, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibitors, interferon alfa 2b, vascular endothelial growth factor receptor 3 (VEGFR-3) inhibitors, and/or other systemic agents targeting lymphatic malformation
• At least 7 days prior to initiation of CERC-006 if receiving topical agents targeting lymphatic malformation

9. Participant has a Karnofsky performance status of ≥50%.

Exclusion Criteria

The presence of any of the following criteria excludes a participant from the study:

1. Participant has a concurrent severe or uncontrolled medical disorder, which could compromise participation in the study.

2. Participant has significant impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of CERC-006.

3. Participant has taken any medication that is a strong cytochrome P450 3A4 (CYP3A4) enzyme inducer or inhibitor within 2 weeks prior to first dose of study drug, or in the opinion of the Investigator, subject may require such medication during the study

4. Participant is receiving chronic treatment with systemic steroids or another immunosuppressive agent, or in the opinion of the Investigator, subject may require such medication during the study

5. Participant has undergone myelosuppressive chemotherapy within 2 weeks, or radiation within 4 weeks prior to first dose of study drug.

6. Participant has a known history of uncontrolled hypertension, cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, heart failure, exercise-related cardiac events including syncope and pre-syncope, or a known family history of sudden cardiac death or ventricular arrhythmia.

7. Participant has received treatment with a medication that has the potential to prolong the QT interval within 1 week prior to the first dose of study drug, or in the opinion of the Investigator, subject may require such medication during the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 31 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Avalo Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's Hospital Colorado

Aurora, Colorado, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

CERC-006-LM-101

Identifier Type: -

Identifier Source: org_study_id