Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615001141538
Ethics application status
Approved
Date submitted
6/10/2015
Date registered
27/10/2015
Date last updated
18/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The second healthy volunteer study assessing the safety, tolerability, and pharmacokinetics (blood levels) of gerilimzumab against placebo.
Scientific title
A Phase I, Randomised, Double-Blind, Placebo-Controlled, Multiple Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Gerilimzumab when Administered Subcutaneously to Healthy Adult Participants
Secondary ID [1] 287346 0
N/A
Universal Trial Number (UTN)
U1111-1173-6339
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 295999 0
Condition category
Condition code
Inflammatory and Immune System 296284 296284 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A total of 18 participants will receive three single subcutaneous doses of gerilimzumab (5 mg or 20 mg) or placebo at Day 1, Day 28, Day 56 .

Each dose will be administered by a train site staff (i.e. nurse) and will be documented in the clinic notes.
Intervention code [1] 292682 0
Treatment: Drugs
Comparator / control treatment
Placebo (10 mM acetate, 9% (w/v) sucrose, 0.006% (w/v) polysorbate 20) subcutaneous injection.
Control group
Placebo

Outcomes
Primary outcome [1] 295936 0
Safety and tolerability of gerilimzumab administered as 3 subcutaneous doses at 4 weekly intervals .

Outcomes are measured by evaluating physical exams, ECGs, vital signs, clinical laboratory results, and adverse events

This is the first time gerilimzumab will be given to humans in multiple doses. Therefore, the risks to human participants have not yet been fully evaluated. Gerilimzumab is a “monoclonal antibody” and while nothing in the non-human drug development data suggest it, it is likely based on other human studies with monoclonal studies, you may experience symptoms of apparent allergic reaction, also known as “cytokine release syndrome”. Symptoms of this can vary but can include:

*Mild to moderate fever, chills, headache, nausea, and vomiting
*Moderate to severe symptoms such as swelling of the skin, low blood pressure, and pulmonary infiltrates (e.g. blood and mucus in the lung).

Although nothing in pre-clinical and preliminary clinical testing of gerilmzumab to date indicates that an allergic reaction is likely, a reaction to any drug is possible. Some symptoms of allergic reactions are:
* Rash
* Wheezing, or difficulty breathing
* Dizziness or fainting (also a possible outcome of a drop in blood pressure)
* Swelling around the mouth, throat or eyes
* A fast pulse
* Sweating

Participants will be closely monitored with regular assessment of vital signs, physical examinations, ECGs, and safety blood results. The study doctor will be looking out for side effects.
Timepoint [1] 295936 0
Day 1 (pre-dose, hours 1, 2, 4, 8, 12, 24 hours post dose), Day 7, 14, 21, 28 (pre-dose, hours 1, 2, 4, 8, 12, 24 hours post dose), 42, 56 (pre-dose, hours 1, 2, 4, 8, 12, 24 hours post dose), 70, and 84
Secondary outcome [1] 316959 0
Pharmacokinetic profile of gerilimzumab administered as 3 subcutaneous doses at 4 weekly intervals

Outcome measured by evaluating pK blood serum samples
Timepoint [1] 316959 0
Day 1 (pre-dose, hour 4, 8, 12, 24 post-dose), Day 7, 14, 21, 28 (pre and post-dose, hour 1, 2, 4, 8, 12, 24 post-dose), 42, 56 (pre-dose, hour 4, 8, 12, 24 post-dose. 70, and 84
Secondary outcome [2] 316960 0
Immunogenicity profile of gerilimzumab administered as 3 subcutaneous doses at 4 weekly intervals

Outcome determined by concentration of anti-gerilimzumab antibodies in a serum assay.
Timepoint [2] 316960 0
Screening, Day 14, 28 (pre-dose), 42, 56 (pre-dose), 84
Secondary outcome [3] 316961 0
Measure changes in the pharmacodynamic marker, C-reactive protein (CRP) over the 12-week dosing and follow-up period

Outcome measured by concentration of c-reactive protein in a serum assay.
Timepoint [3] 316961 0
Screening, Day 14, 28 (pre-dose), 42, 56 (pre-dose, 24 hour post-dose),and 84

Eligibility
Key inclusion criteria
1. 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 PI.
3. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 29.9 (kg/m2) (inclusive).
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 at Day -1.
6. Non-smokers who have not smoked any cigarettes within 6 months prior to screening. No current use of any nicotine containing product. Cotinine levels less than or equal to 5ng/mL.
7. Voluntary consent to participate in the study.
8. Participants using highly effective, double barrier contraception (both male and female partners) during the study and for 4 months following the last 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. One repeat test may be allowed within 7 days at the discretion of the investigator.
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 last 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 >21 units per week and females greater than 14 units per week (1 unit = 0.5 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)
A total of 18 participants will be enrolled into 2 cohorts. Each cohort has 9 participants with 6 randomized to received gerilmzumab ( cohort 1: 5 mg; cohort 2: 20 mg) and 3 participants to receive 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.

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 participant 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.
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
Multiple-dose
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.

Pharmacokinetic 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
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
20/10/2015
Date of last participant enrolment
Anticipated
25/10/2015
Actual
2/11/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4264 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 10207 0
3181 - Prahran

Funding & Sponsors
Funding source category [1] 291908 0
Commercial sector/Industry
Name [1] 291908 0
RuiYi Inc
Country [1] 291908 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] 290576 0
Commercial sector/Industry
Name [1] 290576 0
RuiYi Inc
Address [1] 290576 0
505 Coast Blvd S.
Suite 300
La Jolla, CA 92037
Country [1] 290576 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293415 0
Alfred Health Human Ethics Commitee
Ethics committee address [1] 293415 0
Ethics committee country [1] 293415 0
Australia
Date submitted for ethics approval [1] 293415 0
22/06/2015
Approval date [1] 293415 0
05/08/2015
Ethics approval number [1] 293415 0
330/16

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

Contacts
Principal investigator
Name 59830 0
Dr Jason Lickliter
Address 59830 0
Nucleus Network L5; Burnet Institute AMREP Precinct 89 Commercial Road
Prahran, VIC 3181
Country 59830 0
Australia
Phone 59830 0
+61 3 9076 8960
Fax 59830 0
Email 59830 0
[email protected]
Contact person for public queries
Name 59831 0
Anke Kretz-Rommel, PhD
Address 59831 0
RuiYi Inc
505 Coast Blvd S. Suite 300
La Jolla, CA 92037
Country 59831 0
United States of America
Phone 59831 0
+1 858 587 4815
Fax 59831 0
Email 59831 0
[email protected]
Contact person for scientific queries
Name 59832 0
Anke Kretz-Rommel, PhD
Address 59832 0
RuiYi Inc
505 Coast Blvd S. Suite 300
La Jolla, CA 92037
Country 59832 0
United States of America
Phone 59832 0
+1 858 587 4815
Fax 59832 0
Email 59832 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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