To assess the safety and tolerability of MHS552 of single i.v./s.c. doses. Cohort 1-5 will be i.v. and cohort 6-8 will be s.c. In addition, in each of the 5 first cohorts, a sentinel group is included.
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
All safety endpoints (including physical examination findings, vital signs, ECG
parameters, safety laboratory, adverse events)
Secondary outcome
PK parameters of MHS552 after i.v. and s.c. single doses such as Cmax, Tmax,
AUClast, AUCinf, T1/2, Vz, CL and other PK parameters as appropriate
Background summary
The investigational compound MHS552 consists of (IL-2) molecules harboring a
single point mutation (D49A) into the heavy chain complement determining
region1 (CDR1). This therapeutic Ab has been designed to selectively expand T
regulatory cells (Tregs) and thus restore Treg-mediated immune regulation of T
effector (Teff) responses. MHS552 is in early clinical development for the
treatment of Teff-driven autoimmune and inflammatory diseases, such as
graft-versus-host disease (GvHD), type 1 diabetes (T1D) and vitiligo. The
purpose of this FIH study is to assess the safety and tolerability, PK,
immunogenicity (IG) and PD of single ascending doses (SAD) of MHS552 given by
i.v. infusion and s.c. injection in healthy subjects. The results are intended
to support further clinical development of MHS552 by guiding the dosing
regimens for the assessment of safety, tolerability, PK and PD in future
studies.
Study objective
To assess the safety and tolerability of MHS552 of single i.v./s.c. doses.
Cohort 1-5 will be i.v. and cohort 6-8 will be s.c. In addition, in each of the
5 first cohorts, a sentinel group is included.
Study design
This is a randomized, placebo-controlled, subject-blinded FIH study in healthy
subjects.
Intervention
MHS552, 2 different routes of administration; i.v. and s.c.
Study burden and risks
MHS552 has not yet been administered to human subjects, the in vitro and in
vivo pharmacology of MHS552 has been carefully characterized in primary human
cells and murine models of T1D and GvHD. The toxicology and pharmacokinetics
were also extensively studied in the rat and cynomolgus monkeys, cross reactive
species. Given the limited clinical data on the administration of Treg
selective IL-2 muteins with half-life extension to humans (AMG592 and
RO7049665), the potential risks associated with human use of MHS552 are
inferred from biological understanding of the IL-2 pathway, relevant
non-clinical findings, the general risks associated with therapeutic Ab
administration and, extensive historical clinical experience with the high and
low dose Proleukin® treatment regimens. Based on the data acquired in
non-clinical toxicology studies, potential toxicities to be considered for
MHS552 include reversible hematological effects, skin rashes and lymphocytic or
mixed cellular infiltrates.There is no benefit expected for healthy subjects
participating in this study. The risk to subjects in this trial will be
minimized by adherence to the eligibility criteria, sentinel dosing, close
clinical monitoring, frequent follow-up, minimal duration of the study (single
dose) and prespecified
study stopping rules. The absence, in these healthy subjects, of co-morbid
disease and concomitant immunosuppressive treatment allows for an unbiased
assessment of the safety and tolerability of MHS552 . Based on the clinical
experience with low-dose Proleukin® and from SAD FIH trials of the long-lived
IL-2 muteins AMG592 and RO7049665 in healthy subjects where no class-specific
risks were reported, the risk with single low doses of MHS552 is considered to
be acceptable for healthy subjects.
Lichtstrasse 35
Basel 4056
CH
Lichtstrasse 35
Basel 4056
CH
Listed location countries
Age
Inclusion criteria
Healthy female and male subjects 18 to 45 years of age included, and in good
health as determined by past medical history, physical examination, vital
signs, electrocardiogram, and laboratory tests at screening and/or baseline.
Exclusion criteria
- Women of child-bearing potential, defined as all women physiologically
capable of becoming pregnant
- A history of ongoing, chronic or recurrent infectious disease, or evidence of
tuberculosis infection
- Receipt of live/attenuated vaccine within a 3-month period before first dose
- Active, known, or suspected autoimmune disease or documented history of
autoimmune disease
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004233-33-NL |
| CCMO | NL71107.056.19 |