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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04085666




Registration number
NCT04085666
Ethics application status
Date submitted
3/08/2019
Date registered
11/09/2019
Date last updated
14/09/2020

Titles & IDs
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).
Secondary ID [1] 0 0
CDX6114-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phenylketonuria 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - CDX 6114
Other interventions - Matching Placebo

Experimental: 1st Confinement Period in Unit - Randomized to treatment with either CDX-6114 or matching Placebo

Experimental: 2nd Confinement Period in Unit - Randomized to treatment with either CDX-6114 or matching Placebo


Treatment: Drugs: CDX 6114
CDX-6114 for oral administration is formulated in phosphate buffer, which also includes mannitol and poloxamer.The vehicle solution provided is identical to the CDX-6114 oral solution except for the active drug.

Other interventions: Matching Placebo
The placebo oral dosing solution will also be supplied as an approximately 240 mL oral solution and will be made up of the phosphate buffer diluent and the caramel flavoring.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in concentration of post parandial plasma level of Phe will be summarized over time for each treatment
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Change in concentration of post parandial plasma level of CA will be summarized over time for each treatment
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
Change in the peak Phe concentration in Plasma will be summarized by treatment
Timepoint [3] 0 0
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
Primary outcome [4] 0 0
Change in the peak CA concentration in Plasma will be summarized by treatment
Timepoint [4] 0 0
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
Primary outcome [5] 0 0
Phe Area under the plasma concentration versus time curve (AUC) , over a 5-hour period, following dosing and the standardized breakfast
Timepoint [5] 0 0
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
Primary outcome [6] 0 0
CA Area under the plasma concentration versus time curve (AUC) , over a 5-hour period, following dosing and the standardized breakfast
Timepoint [6] 0 0
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 [1] 0 0
Incidence of Treatment-Emergent Adverse Events (AEs) will be measured
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
The serum levels of CDX-6114 will be summarized descriptively over time
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Absolute values and changes from baseline in blood pressure measurements will be summarized over time for each treatment
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Absolute values and changes from baseline in Heart rate measurements will be summarized over time for each treatment
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Absolute values and changes from baseline in Respiratory rate measurements will be summarized over time for each treatment
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Absolute values and changes from baseline in body temperature (in Fahrenheit or Celsius) measurements will be summarized over time for each treatment
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Absolute values and changes from baseline in 12 lead Electrocardiogram (ECG) measurements will be summarized over time for each treatment
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Absolute values of Weight measurements will be summarized over time for each treatment using a weighing scale in Kg or pounds
Timepoint [8] 0 0
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 outcome [9] 0 0
Absolute blood composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Absolute urine composition values and changes from baseline to the last post-dose time-point will be summarized for each treatment
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
Assesment of the incidence of Treatment-Emergent Antibodies
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
absolute values of height measurements will be summarized over time for each treatment using length measurement scale in centimeters or inches
Timepoint [12] 0 0
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.

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 wine or 12 ounces (360 mL)
of beer or 1.5 ounces (45 mL) of spirits.

10. Patient has a history of regular smoking (daily or most days in a week) or the use of
nicotine products (3 or more nicotine-containing products) who would be unable to
abstain from smoking during the confinement periods in the Phase 1 Unit.

11. Patient has used any recreational drugs of abuse within the 3 months prior to
screening.

12. Patient has a pulse rate = 50 or = 100 bpm; mean systolic blood pressure (SBP) > 140
mmHg; mean diastolic blood pressure (DBP) > 90 mmHg at screening (excluding white-coat
hypertension; therefore, a repeat test showing results within range will be
acceptable).

13. Patient has any clinically significant abnormalities at screening in rhythm,
conduction or morphology of the resting ECG and any clinically significant
abnormalities in the 12-lead ECG, as considered by the PI or delegate, which may
interfere with the interpretation of QTc interval changes including abnormal ST-T wave
morphology.

14. Patient has prolonged QTcF (QT interval corrected for heart rate using Fridericia's
formula) > 450 ms for male patients or > 470 ms for female patients, or a shortened
QTcF < 300 ms or a family history of prolonged QT syndrome, at screening.

15. Patient has any clinically significant abnormalities in clinical chemistry,
haematology, or urinalysis at screening as judged by the PI or delegate, including:
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase
(ALP), gamma glutamyl transferase (GGT) or Total bilirubin (TBL) more than 2.0 times
above the Upper Limit of Normal (ULN).

16. Plasma donation within the 14 days prior to screening or any whole blood
donation/significant blood loss > 500 mL during the 3 months prior to screening.

17. Treatment with any Investigational Drug or Device/Treatment within the 30 days prior
to the first administration of study drug.

18. Use of any prescribed or non-prescribed medication including herbal medicines,
antacids and analgesics (other than anti-hypertensive drugs, oral contraceptives,
paracetamol or multi-vitamins) for the two weeks prior to the initial administration
of the study medication or up to a minimum of 5 times the half-life of the medication
if it has a long half-life.

19. Known allergy or adverse reaction history to any of the oral dose formulation
components e.g. mannitol.

20. Use of Sapropterin (KUVAN) or pegylated phenylalanine ammonia lyase (Palinzyk) or
SYNB1618 or any Phenylalanine-lowering drug within the last 4 weeks.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/08/2020
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Neuss

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Société des Produits Nestlé (SPN)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is an international, multi-center, randomized, double-blind, placebo-controlled,
two-treatment, two-period cross-over study to evaluate the pharmacodynamics, safety,
tolerability and pharmacokinetics of a single oral dose of CDX-6114 in patients with
phenylketonuria (PKU).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04085666
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Damon Bell
Address 0 0
Linear Clinical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04085666