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Trial registered on ANZCTR


Registration number
ACTRN12615000891527
Ethics application status
Approved
Date submitted
10/08/2015
Date registered
26/08/2015
Date last updated
22/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A First in Human study assessing the safety, tolerability and pharmacokinetics (blood levels) of gerilimzumab against placebo.
Scientific title
A Phase I, Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of Gerilimzumab when Administered Subcutaneously to Healthy Adult Participants
Secondary ID [1] 287011 0
N/A
Universal Trial Number (UTN)
U1111-1171-556
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 295476 0
Condition category
Condition code
Inflammatory and Immune System 295730 295730 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involves 4 cohorts:

Cohort 1: single subcutaneous dose of 1 mg of gerilimzumab or placebo
Cohort 2: single subcutaneous dose of 5 mg of gerilimzumab of placebo
Cohort 3: single subcutaneous dose of 15 mg of gerilimzumab or placebo
Cohort 4: single subcutaneous dose of 30 mg of gerilimzumab of placebo
Intervention code [1] 292217 0
Treatment: Drugs
Comparator / control treatment
Placebo (10 mM acetate, 9% (w/v) sucrose, 0.006% (w/v) polysorbate 20)
Control group
Placebo

Outcomes
Primary outcome [1] 295799 0
Safety and tolerability of a single dose of gerilimzumab by evaluating physical exams, ECGs, vital signs, clinical laboratory results, and adverse events
Timepoint [1] 295799 0
Day 1 (pre-dose, hours 1, 2, 4, 6, 8, 10, 12 hours post dose), Day 2, 3, 4, 7, 14, 21, & 30.
Secondary outcome [1] 316544 0
Pharmacokinetic profile of a single dose of gerilimzumab by evaluating pK blood samples
Timepoint [1] 316544 0
Day 1 (pre-dose, hours 4, 6, 8, 10, 12 hours post dose), Day 2, 3, 4, 7, 14, 21, & 30
Secondary outcome [2] 316545 0
Immunogenicity profile as determined by concentration of anti-gerilimzumab antibodies in a serum assay.
Timepoint [2] 316545 0
Screening, Day 7, 14, 30
Secondary outcome [3] 316687 0
Measure changes in the pharmacodynamics marker, c-reactive protein, over the course of 30 days in a serum assay.
Timepoint [3] 316687 0
Screening, Day 7, 14, 30

Eligibility
Key inclusion criteria
1. Adult male and/or females, 18 to 45 years of age (inclusive) at the time of screening.
2. Medically healthy with clinically insignificant screening results (e.g. laboratory profiles, medical history, ECGs, physical exam) as judged by the Principal Investigator.
3. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 29.9 (kg/m2) .
4. Must agree to abstain from alcohol intake 48 hours before administration of study agent and during the inpatient period of the study.
5. Negative urine drug screen /alcohol breath test prior to Day -1.
6. Voluntary consent to participate in the study.
7. Participants using highly effective, double barrier contraception (both male and female partners) during the study and for 4 months following the dose of gerilimzumab.
Males must not donate sperm for at least 4 months post-dose of the last study treatment. Male partners of female patients and female partners of male patients must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle stimulating hormone (FSH) level greater than 40 mIU/mL.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Positive testing for TB, HIV, HBsAg, or HCV.
2. Have any known malignancy or history of malignancy, except basal cell skin cancer that has been treated with no evidence of recurrence for at least 3 months before Day 1.
3. Have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
4. Have any underlying physical or psychological medical condition that, in the opinion of the investigator, would make it unlikely that the participant will complete the study
5. Have evidence of any chronic medical condition (eg, hypertension, elevated cholesterol/triglycerides, asthma, or diabetes).
6. Use of any prescription or over-the counter medication (with the exception of paracetamol) within 7 days of randomization.
7. Have a history of or current elevations in triglycerides that required treatment.
8. Any clinically significant laboratory abnormality
9. Absolute neutrophil count less than 1500/microliter
10. AST or ALT greater than upper limit of normal.
11. History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
12. Blood donation or significant blood loss within 60 days prior to the first study drug administration.
13. Plasma donation within 7 days prior to the first study drug administration.
14. Administration of IP in another clinical trial within 30 days prior to the first study drug administration.
15. Females who are pregnant or lactating. Females should not breast feed for 6 months after the dose of gerilimzumab.
16. Surgery within the past three months prior to the first study drug administration determined by the PI to be clinically relevant.
17. History of cerebrovascular disease, coronary artery disease, seizures, or unexplained syncope.
18. Regular alcohol consumption in males greater than 21 units per week and females greater than 14 units per week (1 unit = 1/2 pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
19. Failure to satisfy the PI of fitness to participate for any other reason.
20. Active infection.
21. History of recurrent infections.
22. Serious local infection or systemic infection within 3 months requiring antibiotic treatment.
23. Any acute illness within 30 days prior to Day 1.

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)
In each cohort of 8, 6 participants will receive gerilimzumab and 2 participants will receive placebo. Each participant will be randomly assigned according to the blinded randomization plan.

The first 8 participants enrolled will be allocated to Cohort 1 and will be randomized to receive a single 1 mg subcutaneous dose of gerilimzumab or placebo.

The second set of 8 participants enrolled will be allocated to Cohort 2 and will be randomized to receive a single 5 mg subcutaneous dose of gerilimzumab or placebo.

The third set 8 participants enrolled will be allocated to Cohort 3 and will be randomized to receive a single 15 mg subcutaneous dose of gerilimzumab or placebo.

The last set of 8 participants enrolled will be allocated to Cohort 4 and will be randomized to receive a single 20 mg subcutaneous dose of gerilimzumab or placebo.

A randomisation list will be generated by an Unblinded Statistician at CNS and will be transferred electronically to the Investigational Site at least 2 days prior to enrolment of participants for each cohort.

Eligible subjects enrolled into the study will be assigned a randomisation number by the Nucleus Network Unblinded Pharmacist in accordance with the Randomization List generated by CNS.

The Randomisation List details the randomisation numbers and the associated treatment.

Each subject will receive the treatment which corresponds to their randomisation number (as assigned in the Randomisation List).

The Randomisation List will be available only to clinic pharmacy staff preparing the drug who are not involved in any other aspect of the study. The Randomisation List will not be made available to the Sponsor, subjects, or members of the staff responsible for the monitoring and evaluation of safety assessments (i.e. all blinded study members) until study completion and database lock, unless a full unblinding of the study is required.

The first two eligible participants will be dosed at least 24 hours before the remaining 6 in cohort 1 & 2.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The generation of the Randomisation List for each cohort will be performed by a CNS Unblinded Biostatistician using the computer program SAS (registered trademark) v9.4 or later.
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
Parallel
Other design features
Single ascending dose
Dose escalation only occurs after safety review by safety monitoring committee
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Safety population: All participants who are dosed will be included in the safety population.

Pharmacokinetc population: The pharmacokinetic population will include all participants having sufficient serum concentration-time data to determine at least 1 pharmacokinetic parameter.

The sample size chosen for this study was selected without statistical considerations. It has been determined adequate to meet the study objectives

No formal inferential statistics will be performed on safety assessments. Listings and summaries for all safety data will be presented using the Safety Population.

Descriptive statistics (mean, SD, median, minimum and maximum) will be calculated for summaries of continuous safety data and frequency counts and percentages (where appropriate) will be calculated for summaries of discrete/categorical safety data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/08/2015
Actual
18/08/2015
Date of last participant enrolment
Anticipated
14/10/2015
Actual
14/10/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4417 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 10083 0
3181 - Prahran

Funding & Sponsors
Funding source category [1] 291819 0
Commercial sector/Industry
Name [1] 291819 0
RuiYi Inc
Country [1] 291819 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
Level 4, 88 Jephson St, TOOWONG QLD 4066
Country
Australia
Secondary sponsor category [1] 290482 0
Commercial sector/Industry
Name [1] 290482 0
RuiYi Inc
Address [1] 290482 0
505 Coast Blvd S.
Suite 300
La Jolla, CA 92037
Country [1] 290482 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293337 0
Alfred Health Human Ethics Committee
Ethics committee address [1] 293337 0
Commercial Road
Prahran, VIC 3181
Ethics committee country [1] 293337 0
Australia
Date submitted for ethics approval [1] 293337 0
22/06/2015
Approval date [1] 293337 0
05/08/2015
Ethics approval number [1] 293337 0
330/15

Summary
Brief summary
This is a first in human trial testing the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of gerilimzumab. Four doses (1 mg, 5 mg, 15 mg, and 30 mg) will be tested in a sequential manner. After the completion of Day 7 at each dose level, a safety monitoring committee will meet and review blinded data to date. They will decide if the study should continue as planned. Only at that time will the next dose level be enrolled.

This is a randomized, double-blind, placebo-controlled, single ascending dose study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58486 0
Dr Jason Lickliter
Address 58486 0
Nucleus Network
L5; Burnet Institute
AMREP Precinct
89 Commercial Road
Prahran, VIC 3181
Country 58486 0
Australia
Phone 58486 0
+61 3 9076 8960
Fax 58486 0
Email 58486 0
[email protected]
Contact person for public queries
Name 58487 0
Anke Kretz-Rommel, PhD
Address 58487 0
RuiYi Inc
505 Coast Blvd S.
Suite 300
La Jolla, CA 92037
Country 58487 0
United States of America
Phone 58487 0
+1 858 587 4815
Fax 58487 0
Email 58487 0
[email protected]
Contact person for scientific queries
Name 58488 0
Anke Kretz-Rommel, PhD
Address 58488 0
RuiYi Inc
505 Coast Blvd S.
Suite 300
La Jolla, CA 92037
Country 58488 0
United States of America
Phone 58488 0
+1 858 587 4815
Fax 58488 0
Email 58488 0
[email protected]

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No Supporting Document Provided



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