CompletedPhase 2ACTRN12618001031257

A Phase 2, Randomized, Double Crossover, Open-Label, Active-Controlled Proof-of-Concept Study of CNSA-001 in Phenylketonuria Patients

Sponsor

Censa Pharmaceuticals Australia Pty Ltd

Enrollment

30 participants

Start Date

Oct 24, 2018

Study Type

Interventional

Conditions

Phenylketonuria

Summary

CNSA-001 represents the first viable formulation of sepiapterin intended for the treatment of hyperphenylalaninemia (HPA) in PKU patients. This Phase 2 study will assess 2 doses of CNSA-001 in comparison to the maximum recommended dose of Kuvan. This is a proof-of-concept (PoC) study that will help to establish dose selection and support the design of future Phase 2/3 studies in PKU patients.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria13

Informed consent
Male or female patients greater than or equal 18 and less than or equal to 60 years of age
Blood Phe level greater than or equal to 450 µmol/L anytime during Screening, or blood Phe level great than or equal to 450 µmol/L when taking the average of the 3 most recent Phe levels from the patient’s medical history (inclusive of the Screening value)
Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least 1 blood Phe measurement greater than or equal to 360 µmol/L
Females must be either postmenopausal for great than or equal to 1 year or surgically sterile (having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months or, if of childbearing potential and not abstinent, willing to use a highly effective method of contraception throughout the study such as 1 of the following:
Hormonal contraception (stable dose for 3 months)
Intrauterine device/Intrauterine Hormone-releasing System
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom)
Females who are abstinent will not be required to use a contraceptive method unless they become sexually active.
Males (if sexually active and nonsterile) with female partners of childbearing potential must be using highly effective birth control measures when sexually active (e.g., less than 1% failure rate/year barrier protection method such as condom), and willing to continue to use such highly effective birth control measures while participating in the study (and for 90 days following participation in study). Males must also refrain from sperm donations during this time period.
Willing and able to comply with the protocol and study procedures
Willing to continue current diet unchanged while participating in the study
Have not used tobacco (e.g., cigarettes, e-cigarettes, cigars, smokeless tobacco, nicotine replacement) for 2 weeks prior to Day -8 and willingness to abstain from these products through EOS.

Exclusion Criteria13

The individual, in the opinion of the Investigator, is unwilling or unable to adhere to the requirements of the study
Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, peptic ulcer disease, etc.) that could affect the absorption of study drug
History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy
Inability to tolerate oral medication
History of allergies or adverse reactions to tetrahydrobiopterin (BH4) or related compounds, or to any excipients in the study drug formulation
Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to Screening
Any clinically significant laboratory abnormality. In general, each laboratory value from Screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range, unless deemed not clinically significant by the Investigator
A female who is pregnant or breastfeeding, or considering pregnancy
Serious neuropsychiatric illness (e.g., major depression) not currently under medical control, that in the opinion of the Investigator or Sponsor, would interfere with the patient’s ability to participate in the study or increase the risk of participation for that patient
Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate)
Clinical diagnosis of primary BH4 deficiency
Major surgery within the prior 90 days
History of alcohol or drug abuse within 6 months prior to Screening or current evidence of substance dependence as determined by the Investigator

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Interventions

Study PKU-002 is a Phase 2, randomized, double crossover, open-label, active-controlled Proof of Concept study of CNSA-001 (sepiapterin) powder for suspension in patients with PKU. This is an outpatient study in which approximately 30 patients will be enrolled at approximately 5 centers. All eligible patients will be randomized to 1 of 6 sequence groups consisting of up to 5 patients each (4 minimum, 5 maximum). Each sequence group will include 3 treatment periods in which patients will receive each of the following open-label treatments for 7 days in random order: CNSA-001 20 mg/kg/day, CNSA-001 60 mg/kg/day, and Kuvan 20 mg/kg/day. The following are the six assigned Sequence Groups, where Treatment A receives CNSA-001 20mg/kg/day, Treatment B receives CNSA-001 60mg/kg/day and Treatment C recieves Kuvan 20mg/kg/day. All treatments will be administered daily for 7 days. Sequence Group 1 will receive Treatment C in Week 1, Washout in Week 2, Treatment A in Week 3, Washout in Week 4 and Treatment B in Week 5. Sequence Group 2 will receive Treatment A in Week 1, Washout in Week 2, Treatment B in Week 3, Washout in Week 4 and Treatment C in Week 5. Sequence Group 3 will receive Treatment B in Week 1, Washout in Week 2, Treatment C in Week 3, Washout in Week 4 and Treatment A in Week 5. Sequence Group 4 will receive Treatment C in Week 1, Washout in Week 2, Treatment B in Week 3, Washout in Week 4 and Treatment A in Week 5. Sequence Group 5 will received Treatment A in Week 1, Washout in Week 2, Treatment C in Week 3, Washout in Week 4 and Treatment B in Week 5. Sequence Group 6 will received Treatment B in Week 1, Washout in Week 2, Treatment A in Week 3, Washout in Week 4 and Treatment C in Week 5. Dosing will take place daily on Days 1-7 of the treatment periods. Study compliance will be documented in the eCRF and in the participant dosing diary. The dosage, date and time of each oral administration and if the entire dose was taken will be recorded. Kuvan 20mg/kg/day will be provided in tablet form, which the patients will take orally with water. CNSA-001 will be prepared by a pharmacist and provided to the patient as a powder reconstituted in Medisca® Oral Mix (which is commercially available, with microcrystalline cellulose, colloidal silicon dioxide, croscarmellose, ascorbic acid and colorant.)