Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of CDX-6114 in Patients With Phenylketonuria (PKU)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT04085666
• Date of registration: 03/08/2019
• Prospective Registration: No
• Primary sponsor: Nestlé
• Public title: Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of CDX-6114 in Patients With Phenylketonuria (PKU)
• Scientific title: A Phase 1, Multi-center, Randomized, Double-blind, Placebo-controlled, Cross-over Study to Evaluate the Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of a Single Oral Dose of CDX-6114 in Patients With Phenylketonuria (PKU).
• Date of first enrolment: June 1, 2019
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT04085666
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Other. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Australia, Germany

Contacts

• Name: Damon Bell
• Affiliation: Linear Clinical Research

• Name: Tim Heise
• Affiliation: Profil Institut für Stoffwechselforschung GmbH

Key inclusion & exclusion criteria

- Inclusion criteria

1. Male and female patients between the ages of 18 and 55 years (inclusive) with a
diagnosis of classical PKU by either a historical blood Phe concentration of >
1200 mol/L at any time or a genetic diagnosis of PKU.

2. Patients capable of following dietary instructions to maintain protein intake
stable throughout the study duration based on principal investigator and
dietician assessment.

3. Patients with a blood Phe concentration < 1200mol/L at screening.

4. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at
least 50 kg and no more than 100 kg inclusive.

5. Patients must be in good general health, as determined by the PI or delegate,
based on a medical evaluation including detailed medical history, full physical
examination, including blood pressure and pulse rate measurement, 12-lead
electrocardiogram (ECG) and clinical laboratory tests.

6. Male patients (unless surgically sterilised) and their female spouse/partner(s)
who are of childbearing potential:

1. Must agree to stay abstinent (where abstinence is the preferred and usual
life-style of the patient), starting at screening and continuing throughout
the clinical study period, and for 90 days after last study drug
administration.

Or

2. Must be using highly effective contraception starting at screening and
continuing throughout the clinical study period, and for 90 days after last
study drug administration. Highly effective contraception is defined as
follows:

i. Injectable or implantable hormones ii. Intrauterine device iii. Surgical
sterilisation iv. Sterilisation implant device v. Combined oral contraceptives
vi. Use of a condom plus oral or injectable or implantable or intrauterine
contraception

c. These requirements do not apply to participants in a same sex relationship.

7. Male patients must agree not to donate sperm starting at screening and continuing
throughout the clinical study period, and for 90 days after last study drug
administration.

8. Female patients of childbearing potential and their spouse/partner(s):

1. Must agree not to become pregnant during the clinical study period and for
30 days after last study drug administration.

2. Must have a negative serum pregnancy test at screening.

3. If heterosexually active, must agree to consistently use a form of highly
effective contraception, starting at screening and continuing throughout the
clinical study period, and for 30 days after last study drug administration.
Highly effective contraception is defined as follows:

i. Injectable or implantable hormones ii. Intrauterine device iii. Surgical
sterilisation iv. Sterilisation implant device v. Surgical sterilisation of the
male partner vi. Combined oral contraceptives vii. Use of a condom plus oral or
injectable or implantable or intrauterine contraception

Or

d. Must agree to stay abstinent (where abstinence is the preferred and usual
life-style of the patient), starting at screening and continuing throughout the
clinical study period, and for 30 days after last study drug administration.

e. These requirements do not apply to participants in a same sex relationship.

9. Female patients of non-childbearing potential:

1. Must have a confirmed clinical history of sterility (e.g. the patient is
without a uterus).

Or

2. Must be postmenopausal as defined as amenorrhea for at least 1 year prior to
screening and a laboratory confirmed serum follicle stimulating hormone
(FSH) level = 40mIU/mL or similar value considered to be in the menopausal
range.

10. Female patients must agree not to breastfeed from screening, throughout the
clinical study period, and until 90 days after last study drug administration.

11. Female patients must agree not to donate ova from screening, throughout the
clinical study period, and until 90 days after last study drug administration.

12. Patient must be competent to understand the nature of the study and capable of
giving written informed consent. Be willing to report for the scheduled study
visits and communicate to study personnel about adverse events and concomitant
medication use.

13. Patient agrees not to participate in another interventional study while
participating in the present clinical study.

Exclusion criteria

1. Female patient who has been pregnant within the 6 months prior to screening or
breastfeeding within the 3 months prior to screening.

2. Evidence or history of clinically significant haematological, renal, endocrine,
pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
(including drug allergies, but excluding untreated, asymptomatic, seasonal allergies
and childhood asthma) at time of screening.

3. Current or chronic history of gastrointestinal illness or conditions interfering with
normal gastrointestinal anatomy or motility. Examples include gastrointestinal bypass
surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption,
Crohn's disease, ulcerative colitis, irritable bowel syndrome (IBS) or celiac sprue.

4. Evidence or history of gastrointestinal symptoms that could lead to the assumption of
an underlying gastrointestinal impairment.

5. Treatment with any anti-platelet and/or anticoagulant medication.

6. Evidence or history of specific food intolerance. Examples include coeliac disease,
severe lactose or dairy food intolerance or a severe intolerance to any
food/ingredient included in the standard breakfast.

7. Any positive result, on screening, for serum hepatitis B surface antigen (HBsAg),
hepatitis C virus antibodies (HCV) or antibodies to human immunodeficiency virus type
1 (HIV-1) and/or type 2 (HIV-2).

8. A positive drug/alcohol result.

9. Patient has a history of exceeding > 21 units of alcohol/week for male patients or >
14 units of alcohol/week for female patients within the 3 months prior to screening.
One unit of alcohol is equivalent to 5 ounces (150 mL) of win


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Drug: CDX 6114

Other: Matching Placebo

Primary Outcome(s)

Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment [Time Frame: Within 30 minutes, within 10 minutes and immediately prior to dosing, and then at 15 minutes, 30 minutes, 1hours, 1.5, 2,4 and 5hours after dosing on both Day 1 and Day 8]

Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment [Time Frame: Within 30 minutes, within 10 minutes and immediately prior to dosing, and then at 15 minutes, 30 minutes, 1hours, 1.5, 2,4 and 5hours after dosing on both Day 1 and Day 8]

CA Area under the plasma concentration versus time curve (AUC) , over a 5-hour period, following dosing and the standardized breakfast [Time Frame: Within 30 minutes, within 10 minutesand immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Phe Area under the plasma concentration versus time curve (AUC) , over a 5-hour period, following dosing and the standardized breakfast [Time Frame: Within 30 minutes, within 10 minutesand immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Change in the peak CA concentration in Plasma will be summarized by treatment [Time Frame: Within 30 minutes, within 10 minutesand immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Change in the peak Phe concentration in Plasma will be summarized by treatment [Time Frame: Within 30 minutes, within 10 minutesand immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Secondary Outcome(s)

Assesment of the incidence of Treatment-Emergent Antibodies [Time Frame: Assesments will be done on day 1 and day 8. Blood will be collected for analysis within 30 minutes prior to dosing on Day 1 and Day 8 and again at the End of Study Visit ( through study completion , an avearge of 8 to 10 weeks)]

Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

Absolute values of Weight measurements will be summarized over time for each treatment using a weighing scale in Kg or pounds [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1hr, 1.5hr, 2hr, 4hr and 5hr after dosing on both Day 1 and Day 8.]

Absolute blood composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

Absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

Absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

Absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

The serum levels of CDX-6114 will be summarized descriptively over time [Time Frame: Within 30 minutes, within 10 minutes and immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

Incidence of Treatment-Emergent Adverse Events (AEs) will be measured [Time Frame: Within 30 minutes, within 10 minutes and immediately prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8]

Absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1, 1.5, 2, 4 and 5hours after dosing on both Day 1 and Day 8.]

absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches [Time Frame: Within 30 minutes prior to dosing, and then at 15 minutes, 30 minutes, 1hr, 1.5hr, 2hr, 4hr and 5hr after dosing on both Day 1 and Day 8.]

Secondary ID(s)

CDX6114-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors