Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000568415
Ethics application status
Approved
Date submitted
19/04/2016
Date registered
3/05/2016
Date last updated
15/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A multiple dose study to investigate the safety of ACH-0144471 in healthy volunteers
Scientific title
A Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACH-0144471 in Healthy Volunteers
Secondary ID [1] 288647 0
ACH471-002
Universal Trial Number (UTN)
U1111-1181-8776
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complement-mediated diseases. 297825 0
Condition category
Condition code
Inflammatory and Immune System 298000 298000 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive either active (ACH-0144471) or placebo.
A total of 46 subjects in four separate dose cohorts are planned. ACH-0144471 will be administered as multiple doses over a 14-day period. The dosing interval will be determined based on emerging data, and there will be flexibility to explore different dosing frequencies. In order to ensure sufficient placebo subjects for comparison at the first dose level, the first dose cohort will include 16 subjects, randomized 1:1 to active drug and placebo; the remaining dose cohorts will enroll 10 subjects per cohort, randomized 4:1 (8 active drug and 2 placebo).

The dose for the first cohort will be determined based on the data from at least 2 doses in the currently ongoing SAD study (ACTRN12616000082404p) (clinical safety, observed PK/PD relationships). The dosing for the next cohort will proceed at a new dose level/regimen, based on the acceptability of available safety and PD results. This procedure will be repeated for all doses in this study. The maximum dose for this study will be calculated so that the predicted Cmax and AUC0-24 do not exceed the NOAELs observed in nonclinical studies, and may be adjusted upward or downward based on emerging nonclinical and clinical safety, PK, and PD data.

All doses of ACH-0144471 or placebo will be administered orally. Dosing should be at the same time each day. All doses should be administered within 5 minutes of the scheduled time.

All dosing is to occur during subject housing optimizing subject compliance.
Intervention code [1] 294062 0
Treatment: Drugs
Comparator / control treatment
The placebo for ACH-0144471 liquid filled capsules (LFCs) dosage forms will be extemporaneously prepared by the clinical site and/or an alternative approved site. The excipients used in the placebo for ACH-0144471 LFCs will be the same as the excipients used in the active ACH-0144471 LFCs. All excipients will be precedented and have regulatory acceptance. The number of capsules required will be adjusted based on the final doses chosen for each group.
Control group
Placebo

Outcomes
Primary outcome [1] 297516 0
To evaluate the safety and tolerability of multiple, ascending oral doses of ACH-0144471 in healthy volunteers.

This outcome is assessed using the following tests and assessments:
Assessment of AEs/SAEs, recording concomitant medications, obtaining vitals, ECGs and collection of blood and urine samples. Previous Human Experience with ACH-0144471 is limited, not allowing for examples of known/possible adverse reactions/events
Timepoint [1] 297516 0
Days -1 through 14, then approximately weekly through Day 42
Secondary outcome [1] 321279 0
To evaluate the pharmacokinetic (PK) profile of ACH-0144471 in healthy volunteers following administration of multiple ascending oral doses.
This outcome is assessed using the following tests:
Pharmacokinetic Assessments: Serial blood samples will be collected to determine plasma
concentrations of ACH-0144471 and any potential metabolites.
Timepoint [1] 321279 0
Daily for Days 2-3, 6, 8-9, 13, 15-17 & Day 21. For Days, 1, 7, and 14: Serial draws approximately every half hour for 4 hours, then approximately every 2-4 hours through Hour 16, dependent on dose
Secondary outcome [2] 321280 0
To investigate the pharmacodynamic (PD) profile of ACH-0144471 in healthy volunteers following administration of multiple ascending oral doses.
This outcome will be assessed using AP Wieslab and other tests of the complement system
Timepoint [2] 321280 0
Daily for Days 2-3, 6, 8-9, 13, 15-17 & Day 21. For Days, 1, 7, and 14: Serial draws approximately every half hour for 4 hours, then approximately every 2-4 hours through Hour 16, dependent on dose
Secondary outcome [3] 321281 0
To evaluate the relationship between ACH-0144471 multiple-dose pharmacokinetics and pharmacodynamics effects through inhibition of alternative pathway (AP) activity (PK/PD).
This outcome is assessed using the following tests: AP Wieslab and Pharmacokinetic Assessments
Timepoint [3] 321281 0
Daily for Days 2-3, 6, 8-9, 13, 15-17 & Day 21. For Days, 1, 7, and 14: Serial draws approximately every half hour for 4 hours, then approximately every 2-4 hours through Hour 16, dependent on dose

Eligibility
Key inclusion criteria
1. Healthy male and female subjects of any ethnic origin between the ages of 25 and 55 years, inclusive
2. Body mass index (BMI) of 18 to 30 kg/m2 with a minimum body weight of 50 kg
3. Female subjects must be of non-childbearing potential
4. Male subjects must agree to abstinence or use a condom when engaged in sexual activity
Minimum age
25 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or clinically relevant evidence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease in the opinion of the Principal Investigator (PI)
2. Any condition possibly affecting drug absorption (including gastrectomy or cholecystectomy)
3. Subjects with C3 complement protein (C3) or C4 complement protein (C4) >110% of the upper limit or <90% of the lower limit of the reference ranges at Screening
4. Subjects with alternative pathway hemolysis (AH50), or classical pathway hemolysis (CH50) assay results outside the reference ranges at Screening
5. Body temperature greater than or equal to 38 degrees C on Day – 1 or Day 1, Hour 0
6. History of febrile illness, or other evidence of infection, within 14 days prior to first study drug administration
7. History of meningococcal infection, or a first-degree relative with a history of meningococcal infection
8. Current tobacco users and smokers (defined as the use of any tobacco or nicotine-containing product within 3 months prior to first study drug administration) or a positive cotinine test at Screening or Day -1
9. History of hypersensitivity reactions to beta-lactams, penicillin, aminopenicillins, flouroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Study drug components will be shipped to the study center in open-label fashion. An unblinded pharmacist and the associated pharmacy staff at the study site will be responsible for dispensing according to the randomization schedule provided. The unblinded pharmacy staff will affix a blinded, unitdose label to the drug identifying which study subject should receive which dose. All doses will be administered by blinded site staff.
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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/05/2016
Actual
7/06/2016
Date of last participant enrolment
Anticipated
Actual
14/12/2016
Date of last data collection
Anticipated
Actual
4/05/2017
Sample size
Target
46
Accrual to date
Final
45
Recruitment outside Australia
Country [1] 7631 0
New Zealand
State/province [1] 7631 0
Auckland

Funding & Sponsors
Funding source category [1] 293006 0
Commercial sector/Industry
Name [1] 293006 0
Achillion Pharmaceuticals, Inc.
Country [1] 293006 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Achillion Pharmaceuticals, Inc.
Address
300 George Street
New Haven, CT 06511
Country
United States of America
Secondary sponsor category [1] 291784 0
Commercial sector/Industry
Name [1] 291784 0
Clinical Network Services (CNS) Ltd
Address [1] 291784 0
PO Box 78312
Grey Lynn
Auckland 1245
Country [1] 291784 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294515 0
Central Health and Disability Ethic Comittee (HDEC)
Ethics committee address [1] 294515 0
Ethics committee country [1] 294515 0
New Zealand
Date submitted for ethics approval [1] 294515 0
14/04/2016
Approval date [1] 294515 0
20/05/2016
Ethics approval number [1] 294515 0
16/CEN/53

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63982 0
Dr Roderick Ellis-Pegler
Address 63982 0
Auckland Clinical Studies Ltd
Ground Floor
MEDACS House
3 Ferncroft Street
Auckland 1010
Country 63982 0
New Zealand
Phone 63982 0
+6493733474
Fax 63982 0
Email 63982 0
[email protected]
Contact person for public queries
Name 63983 0
Glenn Schulman
Address 63983 0
Achillion Pharmaceuticals, Inc.
300 George Street
New Haven, CT 06511
Country 63983 0
United States of America
Phone 63983 0
+12037525510
Fax 63983 0
Email 63983 0
[email protected]
Contact person for scientific queries
Name 63984 0
Roderick Ellis-Pegler
Address 63984 0
Auckland Clinical Studies Ltd
Ground Floor
MEDACS House
3 Ferncroft Street
Auckland 1010
Country 63984 0
New Zealand
Phone 63984 0
+6493733474
Fax 63984 0
Email 63984 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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