Clinical trial NCT04994002: A Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults With Complex Lymphatic Malformations
Official title: A Phase 1b, Open-Label, Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults (Aged 18-31 Years) With Complex Lymphatic Malformations
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Lymphatic Malformation
Keywords: Lymphatic Malformation
Complex Lymphatic Malformations
CERC-006
Lead sponsor: Avalo Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 31
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety and Tolerability of CERC-006 in Adults (Aged 18-31 Years) with Active, Moderate to Severe Complex Lymphatic Malformations
timeFrame: Up to approximately 6 weeks
Secondary outcomes:
measure: Serum Concentrations of CERC-006
timeFrame: Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)
measure: Change from Baseline in Levels of mTOR Related Pathway Biomarkers
timeFrame: Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)
measure: Change from baseline to end of treatment in radiologic assessment, if clinically indicated and/or clinical signs/symptoms of disease
timeFrame: Baseline (Screening) up to 3 days after last dose of study drug (up to approximately 8 weeks)
measure: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Score
timeFrame: Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)
measure: Change from Baseline in Karnofsky Performance Status Score
timeFrame: Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)
measure: Change from Baseline in Pain Scale Assessment
timeFrame: Baseline (Day 1) up to 3 days after last dose of study drug (up to approximately 4 weeks)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
References: