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Trial registered on ANZCTR


Trial ID
ACTRN12613000651785
Ethics application status
Approved
Date submitted
31/05/2013
Date registered
12/06/2013
Date last updated
12/06/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RPH-203 Following a Single Dose in Healthy Male Volunteers
Scientific title
Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RPH-203 Following a Single Dose in Healthy Male Volunteers
Secondary ID [1] 282605 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone Metastasis 289298 0
Osteoporosis 289352 0
Condition category
Condition code
Cancer 289628 289628 0 0
Bone
Musculoskeletal 289629 289629 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RPH-203 is the active solution stored in 10ml glass vials which contains 40mg RPH-203 in 4ml.

There will be 6 cohorts in this study and will follow the dosing regimen below:

Single dose of 10mg RPH203 administered subcutaneously
Single dose of 30mg RPH203 administered subcutaneously
Single dose of 60mg RPH203 administered subcutaneously
Single dose of 60mg RPH203 administered intravenously
Single dose of 120mg RPH203 administered intravenously
Single dose of 180mg RPH203 administered intravenously

Up to 48 healthy male participants (8 participants per cohort) will be enrolled and assigned to 6 sequential dose cohorts of RPH-203 (10.0mg, 30.0mg, 60.0mg administered subcutaneously and 60.0mg, 120.0mg, 180.0mg administered intravenously) or matching placebo (dummy drug with no active substance). Each participant will have 3 out of 4 chance of receiving the active RPH-203 drug and 1 out 4 chance of receiving the placebo. The assignment will be random, similar to the toss of a coin. As this is a dose escalation study, the first group will receive the lowest dose and when it is determined safe, the second group will receive a higher dose. The same procedure will be performed for each dosing group aside from the route of administration which can be either subcutaneous or intravenous. Participants will be told which group they will take part in and what the dose level will be. As this is the first time this drug is being given in humans, 2 participants from the first dosing group will be given the drug first. 1 will be receiving the active drug and the other will receive the placebo. The assignment will be done at random. The remaining 6 participants will be given the drug at least 48 hours later when the drug is deemed safe. Participants will be advised if they are intended to be the first 2 participants before they come to the unit for dosing. All 8 participants will be dosed together for all other dosing groups. Participants will be admitted and be required to stay in the study unit for 3 days and be required to attend outpatient visits on 5 occasions. This study is being conducted at the Centre for Clinical Studies.

This study will only involve a single dose of the investigational product RPH203 or placebo however the entire duration of the study including screening period is up to 55 days.
Intervention code [1] 287275 0
Treatment: Drugs
Comparator / control treatment
Placebo (sodium chloride) will also be used in each of the treatment cohort and will be administered subcutaneously or intravenously depending on the treatment cohort.
Control group
Placebo

Outcomes
Primary outcome [1] 289716 0
The primary endpoint for this study is the safety and tolerability of RPH-203 which will be assessed using the following:
1. Incidence, nature, relatedness, and severity of adverse events.
2. Change in vital signs and physical examination from baseline.
3. Change in clinical laboratory results and 12-lead ECG results.

As this is the first in human study for RPH-203, there were no previously recorded adverse reactions observed in human. However, based on animal studies in monkeys that were administered with much higher dose levels (more than 10 fold higher) of RPH-203, the following are the most common side effects that have been observed: *Increase in liver enzymes *Increase in creatinine kinase, which is an enzyme that releases energy in your cells *Skin reactions (reddening, bruising)
Timepoint [1] 289716 0
1. The monitoring of adverse events will be performed throughout the study and when reported by the participants.

2. Vital signs will be monitored at screening, the day before dosing (Day -1), Day 1,2,3,7,12,20 and 27. Physical examination will be performed at screening and on the Day 27.

3. ECGs will be monitored at screening, Day 1,2,3,7,12,20 and 27. Clinical laboratory results will be monitored at screening, the day before dosing (Day -1), Day 2,3,7,12,20 and 27.
Secondary outcome [1] 303101 0
the secondary enpoint is PK parameters which will be derived from the serum concentration-time profile of RPH-203 following administration:
*Total exposure (AUC)
*Maximum serum concentration (Cmax)
*Clearance (CL)
*Volume of distribution (Vd)
Other parameters, such as accumulation ratio, elimination half-life, and dose proportionality will also be assessed.
Timepoint [1] 303101 0
PK samples will be collected for analysis at the following timepoints: Predose, 30mins, 1, 2, 4, 8, 9, 10, 11, 12, 16, 24, 48hrs post dose and on Day 7, 12, 20 and 27.

Eligibility
Key inclusion criteria
*Healthy male volunteers age between 18 and 45 years
*Body mass index between 19 and 30 kg/m2
*No clinically significant findings in the medical history and physical examination
*No clinically significant laboratory values and urinalysis, unless the investigator considers any abnormality to be clinically irrelevant
*Normal ECG, blood pressure and heart rate, unless the Investigator considers any abnormality to be Not Clinically Significant (NCS)
*Negative Quantiferon (Registered Trademark) test
*Informed consent obtained in writing for all volunteers at enrolment into the study
Minimum age
18 Years
Maximum age
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Family history of premature Coronary Heart Disease (CHD)
*Any condition requiring the regular use of any medication
*Exposure to prescription medications or to drugs known to interfere with metabolism of drugs within 14 days prior to screening
*Exposure to any other medication, including over-the counter medications, herbal remedies and vitamins 14 days prior to randomization
*Participation in another study with any investigational product within 30 days or 5 half-lives of the investigational product, whichever is greater, before Day 1 of study treatment
*Treatment in the previous 3 months with any drug known to have a well defined potential for toxicity to a major organ
*Current smoker of more than 10 cigarettes or equivalent / day prior to commencing the study, unable to completely stop smoking during the study
*Be in the exclusion period of any previous study with investigational drugs
*Symptoms of a clinically significant illness in the 3 months before the study
*History of significant allergic disease (e.g. medications) and acute phase of allergic rhinitis in the previous 2 weeks before randomization or any food allergy.
*History of autoimmune diseases, such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, etc.
*History of any disease that is known to affect bone, excluding history of bone fracture more than 12 months before the study
*History of renal insufficiency or hepatic insufficiency
*Hypocalcaemia or relevant medical history predisposing volunteers to hypocalcaemia
*Blood or plasma donation of more than 500 ml during the previous 2 months before randomization and/or more than 50 ml in the 2 weeks prior to screening
*Current or history of malignancy disease
*Volunteers at risk for tuberculosis (TB), specifically volunteers with:
*Current clinical, radiographic or laboratory evidence of active TB
*History of active TB unless there is documentation that the prior anti-TB treatment was appropriate in duration and type
*Latent TB which has not been successfully treated
*A positive Quantiferon (Registered Trademark) test at screening or within 6 months prior to Day 1
*Positive test for HIV or prior positive test as confirmed by history
*Positive test for hepatitis B (antigens HBs, antibody HBc) or C, unless caused by immunization
*Current evidence of drug abuse or history of drug abuse within one year prior to screening
*History of alcohol abuse or active alcoholism within 1 year prior to screening i.e. consumption of more than 3 standard drinks per day
*Positive alcohol or urine drug screen at screening
*Mental condition rendering the volunteer incapable to understand the nature, scope, and possible consequences of the study
*Adults under guardianship and people with restriction of freedom by administrative or legal decisions
*Unlikely to comply with the clinical study protocol; e.g. uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study
*Volunteer is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.

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)
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

Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 287387 0
Commercial sector/Industry
Name [1] 287387 0
R-Pharm
Address [1] 287387 0
The North Tower
10 Testovsky str, entr 1, fl 26
123154, Moscow, Russia
Country [1] 287387 0
Russian Federation
Primary sponsor type
Other Collaborative groups
Name
Nucleus Network Limited
Address
Level 5, Burnet Building,
89 Commercial Road
Melbourne 3004 VICTORIA
Australia
Country
Australia
Secondary sponsor category [1] 286132 0
None
Name [1] 286132 0
Address [1] 286132 0
Country [1] 286132 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289359 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 289359 0
55 Commercial Road
Melbourne 3004
VICTORIA
Australia
Ethics committee country [1] 289359 0
Australia
Date submitted for ethics approval [1] 289359 0
27/05/2013
Approval date [1] 289359 0
Ethics approval number [1] 289359 0
265/13

Summary
Brief summary
This study is evaluating the safety, tolerability and pharmacokinetics of RPH-203 following a single dose in health male volunteers as a potential treatment for secondary cancer of the bone. Who is it for? You may be eligible to join this study if you are aged between 18 and 45 years old, have a body mass index between 19kg/m2 and 30kg/m2, have a negative Quantiferon (Registered Trademark) test, male and healthy. Trial details Participants in this study will be randomly (by chance) divided into 6 sequential dose cohorts to receive 10.0mg, 30.0mg, 60.0mg, 120.0mg, 180.0mg of RPH-203 or matching placebo. Cohorts will receive a single dose of 10.0mg, 30.0mg or 60.0mg of RPH-203 subcutaneously, or a single dose of 60.0mg, 120.0mg or 180.0mg intravenously. As this is a dose escalation study, the first group will receive the lowest dose and when it is determined safe, the second group will receive a higher dose. Participants will be told which group they will take part in and what the dose level will be. As this is the first time this drug is being given in humans, 2 participants from the first dosing group will be given the drug first. 1 will be receiving the active drug and the other will receive the placebo. The assignment will be done at random. The remaining 6 participants will be given the drug at least 48 hours later when the drug is deemed safe. Participants will be advised if they are intended to be the first 2 participants before they come to the unit for dosing. All 8 participants will be dosed together for all other dosing groups. Participants will be admitted and be required to stay in the study unit for 3 days and be required to attend outpatient visits on 5 occasions for monitoring and assessment. This study is being conducted at the Centre for Clinical Studies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40462 0
Dr Jason Lickliter
Address 40462 0
Nucleus Network
Level 5, Burnet Building
89 Commercial Road
Melbourne 3004
VIC
Country 40462 0
Australia
Phone 40462 0
+613 9076 8906
Fax 40462 0
Email 40462 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 40463 0
Mr Jeffery Wong
Address 40463 0
Nucleus Network
Level 5, Burnet Building
89 Commercial Road
Melbourne 3004
VIC
Country 40463 0
Australia
Phone 40463 0
+613 9076 8909
Fax 40463 0
Email 40463 0
j.wong@nucleusnetwork.com.au
Contact person for scientific queries
Name 40464 0
Mr Jeffery Wong
Address 40464 0
Nucleus Network
Level 5, Burnet Building
89 Commercial Road
Melbourne 3004
VIC
Country 40464 0
Australia
Phone 40464 0
+613 9076 8909
Fax 40464 0
Email 40464 0
j.wong@nucleusnetwork.com.au