Clinical trial NCT04256655: Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
Official title: A Phase 1, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 After Multiple Ascending Oral Dose Administration to Patients With Phenylketonuria (PKU).
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Phenylketonurias
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is of this Phase 1 study is to evaluate the safety and tolerability of daily, multiple, oral doses of CDX-6114 when administered to patients with PKU for 14 days. The aim is to check if administration of daily, multiple, oral doses of CDX-6114 to patients with PKU for 14 days shows a clinically acceptable safety and tolerability profile.


Eligibility criteria: Inclusion Criteria

1. Male and female patients between the ages of 18 and 65 years, with a diagnosis of classical PKU
2. Patients with a blood phenylalanine concentration \> 600mol/L at screening as an indicator of sub-optimal dietary management
3. Body mass index (BMI) between 18 and 35 kg/m2 at screening.
4. Male patients must agree not to donate sperm starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration
5. Female patients of childbearing potential and their spouse/partner
6. Female patients of non-childbearing potential:
7. Female patients must agree not to breastfeed. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
8. Female patients must agree not to donate ova. This includes the period starting at screening and continuing throughout the clinical study period up to 90 days after last study drug administration.
9. Patients must be deemed competent to understand the nature of the study and capable of giving written informed consent. Patients must also be willing to attend scheduled study visits in person and to reliably communicate to study personnel on adverse events and concomitant medication use.
10. Patients must agree not to participate in another interventional study while participating in the present clinical study.

Exclusion Criteria

1. Presence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease/condition (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma).
2. Presence or history of gastrointestinal illness or conditions interfering with normal gastrointestinal anatomy. Examples include gastrointestinal bypass surgery, cholecystectomy, partial or total gastrectomy, gastric band surgery, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or coeliac disease.
3. Active treatment with any platelet aggregation inhibitor and/or active treatment (or within the last 4 weeks) with anticoagulant medication.
4. Presence or history of specific food intolerance. Examples include coeliac disease, severe lactose or dairy food intolerance.
5. Positive result for serum hepatitis B surface antigen (HBsAg), hepatitis A virus antibodies (HAV), hepatitis C virus antibodies (HCV), or antibodies to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2) at Screening.

Primary outcomes:
measure: Change in the incidence of Treatment-Emergent Adverse Events (AEs) will be measured
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in the serum levels of CDX-6114 will be summarized descriptively over time
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values of Weight measurements will be summarized over time for each treatment using a weighing scale in Kg or pounds over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute blood composition values from baseline to the last post-dose time-point will be summarized for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Any change in the incidence of treatment-Emergent Antibodies will be assesed
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
Secondary outcomes:
measure: Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in the peak Phe concentration in Plasma will be summarized by treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in the peak CA concentration in Plasma will be summarized by treatment
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Phe Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: CA Area under the plasma concentration versus time curve (AUC) , over a 24 hour period, following dosing and the standardized meal
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Serum concentrations of CDX-6114 over a 24 hour period, following dosing and thestandardized meal
timeFrame: Within 0.25min , 0.5min , 1hours, 2hours, 5hours (immediately prior to starting lunch), 7.5hours, 11.5 hours(immediately prior to starting the evening meal), 14hours and 16 hours after the first dose of study medication on both day 1 and day 14
measure: Change in attention
timeFrame: The questionnaire will be completed at home by the patient on Day -1 and on Day 13 before each in-house period
measure: Change in mood
timeFrame: The questionnaire will be completed at home by the patient on Day -1 and Day 13 before each in-house period. The POMS-2 questionnaire used is the full-length adult (18+ years) version (POMS 2-A).
Other outcomes:
Locations:
Study officials:
affiliation: Global Development Lead - GI care
name: Tiago Nunes, MD PhD
role: STUDY_DIRECTOR
References: