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Trial registered on ANZCTR


Registration number
ACTRN12621001571864
Ethics application status
Approved
Date submitted
7/10/2021
Date registered
18/11/2021
Date last updated
25/07/2024
Date data sharing statement initially provided
18/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
First-in-Human Study of RLYB116 in Healthy Participants
Scientific title
Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RLYB116 in Healthy Participants
Secondary ID [1] 305326 0
IPC2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
complement mediated diseases 323694 0
Condition category
Condition code
Blood 321184 321184 0 0
Haematological diseases
Inflammatory and Immune System 321228 321228 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
RLYB116 is being developed for administration for the treatment of complement mediated diseases. RLYB116 is a small protein composed of an Affibody® Z-domain that binds with high affinity to C5, inhibiting terminal complement activation, and an albumin binding domain (ABD) that extends the effective plasma half-life of the protein by targeting serum albumin.

The study consists of two parts:
Part A (Single Ascending Dose): The participant will be randomized in 3:1. The total of 5 ascending dose cohorts are planned to be dosed in a sequential manner in Part A of the study.
Total of 8 participants will be enrolled in each dose level and the 6 participants will receive RLYB116 per dose level and 2 participants will receive matching placebo in each dose level.
Dose level 1: 2mg administered subcutaneously once on Day 1
Dose level 2: 10 mg administered subcutaneously once on Day 1
Dose level 3: 30 mg administered subcutaneously once on Day 1
Dose level 4: 100 mg administered subcutaneously once on Day 1
Dose level 5: 300 mg administered subcutaneously once on Day 1

Each cohort will be administered to a distinct group of subjects and escalation to the next higher dose level will occur only after completion of a review of clinical safety and available pharmacokinetic data by the Safety Review Committee.

Part B (Multiple Ascending Dose): The participant will be randomized 5:1. Four cohorts will be executed sequentially.
Total of 12 participants will be enrolled in each dose level and the 10 participants will receive RLYB116 per dose level and 2 participants will receive matching placebo in each dose level.
The multiple dose phase may initiate after the Safety Review Committee review of the safety data from the fifth cohort of the single dose phase and agreement on the study proceeding. 
Dose level 1 (B1): 100 mg administered subcutaneously once on Day 1, Day 8, Day 15, Day 22, Day 29
Dose level 2 (B4):  100 mg administered subcutaneously once on Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29
Dose level 3 (B2):  Less than or equal to 150mg administered subcutaneously once on Day 1, Day 8, Day 15, Day 22, Day 29
Dose level 4 (B7):  Less than or equal to 125 mg administered subcutaneously once on Day 1, Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, Day 25, Day 29

The planned multiple dose cohorts may be adjusted for the dose selected or the number of cohorts based on emergent safety, tolerability, pharmacokinetic, or pharmacodynamic data from the study for both the part A and B.

In both the Part A and Part B, the RLYB116 will be administered in the unit at the specified times under supervision by principal investigator and intervention adherence will be monitored by study staff.
Intervention code [1] 321736 0
Treatment: Drugs
Comparator / control treatment
Placebo is sodium chloride injection, 0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 328975 0
Part A/Part B: To assess the safety and tolerability of RLYB116 in healthy participants following single and repeated administration adverse events
• Incidence and severity of adverse events (AE) (Adverse events will be coded using the Medical Dictionary for Regulatory Activities)
• vital signs (Tympanic temperature, pulse rate, respiratory rate via pulse oximeter and blood pressure by sphygmomanometer)
• clinical laboratory values (Hematology, clinical chemistry and Coagulation) measured using blood samples
• electrocardiogram (ECG)
Timepoint [1] 328975 0
Part A: From baseline to Day 1, Day 2, Day 3, Day 4, Day 5, Day 8, Day 15, Day 29, Day 43, Day 57, and Day 71 post-intervention administration.

Part B: From baseline to Day 1, Day 2, Day 3, Day 4, Day 5, Day 8, Day 9, Day 11 (B7 only), Day 15, Day 16, Day 18 (B7 only), Day 22, Day 23, Day 25 (B7 only), Day 29, Day 30, Day 32, Day 33, Day 36, Day 43, Day 57, Day 71 and Day 99 post-intervention administration.
Secondary outcome [1] 401172 0
Part A/Part B: To assess the pharmacokinetic (PK) profile of RLYB116 following subcutaneous administration.
The following parameters are used for the pharmacokinetic assessment:
1. half-life (t1/2)
2. maximum serum concentration (Cmax)
3. time to maximum serum concentration (Tmax)
4. clearance (CL)
5. volume of distribution (Vd)
6. area under the concentration time curve (AUC)
Timepoint [1] 401172 0
Part A: Blood samples for PK will be collected pre dose, and then at 2hrs, 4hrs, 12hrs, 24hrs, 36hrs, 48hrs, 60hrs, 72hrs, 84hrs, 96hrs, 8 days, 15 days, 29 days, 43 days, 57 days, and 71 days post dose.

Part B: Blood samples for PK will be collected pre dose, and then at 2hrs, 4hrs, 12hrs, 24hrs, 36hrs, 48hrs, 60hrs, 72hrs, 84hrs, 96hrs, 8 days, 11 days (B7 only), 15 days, 18 days (B7 only), 22 days (B2 and B7 only), 25 days (B7 only), 29 days, 36 days (B2 and B7 only), 43 days, 57 days, 71 days, and 99 days post dose. On Day 29, samples are collected pre dose and then at 2hrs, 4hrs, 12hrs, 24hrs, 72hrs, and 96hrs post dose.
Secondary outcome [2] 402426 0
Part A/ Part B: To characterize the pharmacodynamic (PD) properties of RLYB116 following single and repeated administration to healthy participants
The pharmacodynamic analysis will include assessment of the impact of RLYB116 administration on serum concentration of components of the complement system by measurement of free C5 concentrations and total C5 concentrations.
Blood sample will be collected for pharmacodynamic analysis
Timepoint [2] 402426 0
Part A: Blood sample will be collected at pre dose and 2, 4, 12 hours post dose and Day 1, Day 2, and Day 4 post-first dose.

Part B: Blood sample will be collected at pre dose and 12 hours post dose and Day 1, Day 2, Day 8, Day 11 (B7 only), Day 15, Day 18 (B7 only), Day 22 (B2 and B7 only), Day 25 (B7 only), Day 29, Day 30, Day 32, Day 33, Day 36 (B2 and B7 only), Day 43, Day 57, Day 71, and Day 99 post-first dose.

Eligibility
Key inclusion criteria
1. Males and females age 18 to 55 years.
2. Able to provide written informed consent.
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2.
4. Must have been vaccinated against N. meningitidis and S. pneumoniae with approved vaccine according to product label. All participants considered eligible for enrollment will be vaccinated according to the following:
a. Vaccination with Meningococcal Group A, C, W135, and Y conjugate vaccine (Menveo®) + Pneumococcal Polysaccharide Vaccine (Pneumovax® 23) at least 28 days prior to receiving the first dose of RLYB116.
b. Vaccination with Meningococcal Group B (Bexsero®) at least 14 days prior to receiving the first dose of RLYB116.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participants that smoke more than 10 cigarettes per week.
2. Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus.
3. Pregnant or nursing.
4. Donation or loss of greater than 400 mL of blood within 56 days of study enrollment.
5. History of severe hypersensitivity to any drug, including penicillin or ciprofloxacin, or to N. meningitidis or S. pneumoniae vaccines.

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)
The participants will be assigned a unique number (randomization number) in ascending numerical order at each study site.
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 design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/02/2022
Actual
22/02/2022
Date of last participant enrolment
Anticipated
31/12/2023
Actual
4/08/2023
Date of last data collection
Anticipated
31/03/2024
Actual
25/01/2024
Sample size
Target
88
Accrual to date
Final
89
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 23958 0
Nucleus Network - Melbourne
Recruitment hospital [2] 20566 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 35348 0
4007 - Herston
Recruitment postcode(s) [2] 39447 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 309693 0
Commercial sector/Industry
Name [1] 309693 0
IPC Research, LLC
Country [1] 309693 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
IPC Research, LLC
Address
234 Church Street
Suite 1020,
New Haven, CT 06510
Country
United States of America
Secondary sponsor category [1] 310717 0
None
Name [1] 310717 0
Address [1] 310717 0
Country [1] 310717 0
Other collaborator category [1] 281986 0
Commercial sector/Industry
Name [1] 281986 0
Novotech (Australia) Pty Limited
Address [1] 281986 0
Level 3, 235 Pyrmont street, Pyrmont NSW 2009
Country [1] 281986 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309462 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 309462 0
Ethics committee country [1] 309462 0
Australia
Date submitted for ethics approval [1] 309462 0
06/10/2021
Approval date [1] 309462 0
29/10/2021
Ethics approval number [1] 309462 0
590/21 (HREC/80188/Alfred-2021)

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

Contacts
Principal investigator
Name 114238 0
Dr Richard Friend
Address 114238 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 114238 0
Australia
Phone 114238 0
+61 7 3707 2700
Fax 114238 0
Email 114238 0
r.friend@nucleusnetwork.com.au
Contact person for public queries
Name 114239 0
Jackie Schumacher
Address 114239 0
IPC Research LLC
234 Church Street, Suite 1020
New Haven, CT 06510
Country 114239 0
United States of America
Phone 114239 0
+1 203 859 3820
Fax 114239 0
Email 114239 0
regulatory@rallybio.com
Contact person for scientific queries
Name 114240 0
Jackie Schumacher
Address 114240 0
IPC Research LLC
234 Church Street, Suite 1020
New Haven, CT 06510
Country 114240 0
United States of America
Phone 114240 0
+1 203 859 3820
Fax 114240 0
Email 114240 0
regulatory@rallybio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.