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

NCT04994002 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: CERC-006-LM-101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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

Keywords

Lymphatic Malformation; Complex Lymphatic Malformations; CERC-006

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of CERC-006 in Adults (Aged 18-31 Years) with Active, Moderate to Severe Complex Lymphatic Malformations

  Safety and tolerability will be assessed by incidence of adverse events (AEs). Clinically significant changes from baseline in vital signs, ocular exams, cardiology tests including echocardiogram (ECHO) and electrocardiogram (ECG), and clinical laboratory results will be recorded as AEs.

  Up to approximately 6 weeks

Secondary Outcomes (6)

• Serum Concentrations of CERC-006

  Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)

• Change from Baseline in Levels of mTOR Related Pathway Biomarkers

  Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)

• Change from baseline to end of treatment in radiologic assessment, if clinically indicated and/or clinical signs/symptoms of disease

  Baseline (Screening) up to 3 days after last dose of study drug (up to approximately 8 weeks)

• Change from Baseline in 36-Item Short Form Health Survey (SF-36) Score

  Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)

• Change from Baseline in Karnofsky Performance Status Score

  Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)

Study Arms (2)

Cohort 1: CERC-006 (0.5 mg)

EXPERIMENTAL

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

Drug: CERC-006

Cohort 2: CERC-006 (1 mg)

EXPERIMENTAL

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.

Drug: CERC-006

Interventions

CERC-006 DRUG

Oral solution

Cohort 1: CERC-006 (0.5 mg); Cohort 2: CERC-006 (1 mg)

Eligibility Criteria

• Age: 18 Years - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must fulfill the following requirements to be eligible for the study:
• Participant is 18 to 31 years of age (inclusive) at the time of consent.
• 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.
• Participant's complex lymphatic malformation is considered, in the opinion of the investigator, to be moderate to severe.
• 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
• Participant has fasting low-density lipoprotein (LDL) of \<160 mg/dL.
• 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
• 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

You may not qualify if:

• The presence of any of the following criteria excludes a participant from the study:
• Participant has a concurrent severe or uncontrolled medical disorder, which could compromise participation in the study.
• Participant has significant impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of CERC-006.
• 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
• 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
• Participant has undergone myelosuppressive chemotherapy within 2 weeks, or radiation within 4 weeks prior to first dose of study drug.
• 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.
• 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.

Sponsors & Collaborators

• Avalo Therapeutics, Inc.: lead

Study Sites (3)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Lymphatic Abnormalities

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: August 6, 2021
• Study Start: September 3, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: March 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)