The primary objective of the study is:• To evaluate the clinical efficacy of rozanolixizumab as a treatment for subjects with CIDPThe secondary objectives of the study are:• To evaluate the safety and tolerability of rozanolixizumab sc infusion in…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the change from Baseline to Week 13 (Day 85)
in iRODS score.
Further variables include values and change from Baseline in maximum grip
strength score recorded by site personnel at each scheduled assessment during
the Treatment and Observation Periods; values and change from Baseline in daily
maximum grip strength score recorded by the subject each day during the
Treatment and Observation Periods; additional patient-reported outcomes (PROs);
values and change from Baseline in Rasch-built, modified interval Medical
Research Council scale (RT-MRC) sum score at each scheduled assessment during
the Treatment and Observation Periods; and subjects receiving rescue medication
and time to rescue medication administration.
Secondary outcome
• Subject experienced CIDP relapse (iRODS) up to Week 13 (Day 85) after first
treatment and time to CIDP relapse (iRODS) at each scheduled assessment during
the Treatment Period, where CIDP relapse (iRODS) is defined as a clinically
important deterioration from Baseline in iRODS score, ie, a minimum clinically
important differences-standard error (MCID-SE) of <= 1.96. Values and change
from Baseline in iRODS scores at each scheduled assessment during the Treatment
and Observation Periods will be assessed.
• Subject experienced CIDP relapse up to Week 13 (Day 85) after first treatment
and time to CIDP relapse during the Treatment Period will be determined using
the adjusted INCAT disability score where CIDP relapse is defined as an
increase from Baseline of at least 1 point in the adjusted INCAT score. Values
and change from Baseline in adjusted INCAT score at each scheduled assessment
during the Treatment and Observation Periods will be assessed.
• Subject experienced CIDP relapse up to Week 13 (Day 85) after first treatment
and time to CIDP relapse during the Treatment Period will be determined using
maximum grip strength assessed by the site personnel, where CIDP relapse is
defined as a clinically important deterioration from Baseline in grip strength,
ie, a decline of >14kPa.
Other and exploratory variables include: safety and tolerability variables,
pharmacokinetic (PK), pharmacodynamic (PD), immunologic variables, exploratory
pharmacogenetics variables, and exploratory ribonucleic acid (RNA), proteins,
and metabolites biomarkers. Plasma concentration of rozanolixizumab over time
will be assessed as the PK variable. The PD variables are minimum and maximum
decrease from Baseline in total IgG concentration during the study; value and
change from Baseline in IgG concentrations at each scheduled assessment during
Treatment and Observation Periods; value and change from Baseline in IgG
subclass concentrations at each scheduled assessment during Treatment and
Observation Periods; and value and change from Baseline in neurofilament light
chain (NF-L) levels at each scheduled assessment during Treatment and
Observation Periods. Immunological variables will also be assessed.
Safety and tolerability variables will include occurrence of treatment-emergent
adverse events (TEAEs); TEAEs leading to withdrawal of IMP; vital sign values
and changes from Baseline (systolic and diastolic blood pressure [BP],
temperature, pulse rate, and body weight) at each scheduled assessment during
Treatment and Observation Periods; 12 lead electrocardiogram (ECG) parameters
and change from Baseline at each scheduled assessment during Treatment and
Observation Periods; laboratory values and changes from Baseline at each
scheduled assessment during Treatment and Observation Periods (hematology,
clinical chemistry, and urinalysis); tuberculosis (TB) evaluation; and values
and change from Baseline in concentrations of total protein, albumin, α and β
globulins at each scheduled assessment during the Treatment and Observation
Periods.
Background summary
Production of pathogenic auto-antibodies is a major feature of a number of
autoimmune diseases
often associated with a specific pathomechanism. Cellular and humoral immune
mechanisms are
thought to be involved in the pathogenesis of CIDP resulting in inflammatory
lesions in the
spinal roots, proximal nerve trunks, and along the peripheral nerves. The
essential role of the
autoimmune antibodies in mediating this pathology is supported by the
improvement seen after
PLEX and IA. Identification of the specific antigenic target(s) of the
autoimmune antibodies in
CIDP is expanding with recent immunological techniques. Treatments aimed at
reducing the
quantity of circulating IgG auto-antibodies are being used for primary and
secondary therapy of
autoimmune diseases, particularly where corticosteroid-based immune suppression
is not or no
longer effective. The therapeutic approach of these treatments is based on
lowering levels of
pathogenic auto-antibodies, which represents rational and effective treatment
modalities of
autoimmune diseases.
Rozanolixizumab is a humanized IgG4 monoclonal antibody that is being developed
as an
inhibitor of the activity of FcRn. The FcRn recycles IgG and albumin and
transports it
bidirectionally across epithelial barriers. Recent studies have shown that FcRn
rescues both IgG
and albumin from intracellular lysosomal degradation by recycling it from the
sorting endosome
to the cell surface (Anderson et al, 2006). Rozanolixizumab has been
specifically designed to
block IgG binding to FcRn without blocking the binding and recycling of
albumin. By blocking
the activity of FcRn, rozanolixizumab accelerates the catabolism of IgG
antibodies, including
IgG auto-antibodies. The aim is to reduce the concentration of pathogenic IgG
in patients with
autoimmune diseases mediated by the action of IgG auto-antibodies.
Study objective
The primary objective of the study is:
• To evaluate the clinical efficacy of rozanolixizumab as a treatment for
subjects with CIDP
The secondary objectives of the study are:
• To evaluate the safety and tolerability of rozanolixizumab sc infusion in
subjects with CIDP
• To assess the PD effect of rozanolixizumab as measured by the total IgG
concentrations in serum
Exploratory objectives are:
• To evaluate the effects of rozanolixizumab on the concentration of total
protein, albumin, α and β globulins, IgG subclasses, IgM, IgA, and IgE, serum
and plasma complement levels
• To evaluate the incidence and emergence of anti-drug antibody (ADA) with
respect to immunogenicity and PK and PD
• To evaluate the effect of rozanolixizumab on complement and cytokines
• To assess the plasma concentrations of rozanolixizumab administered by sc
infusion
• To assess the PD effect of rozanolixizumab as measured by NF-L in serum
• To assess the effect of rozanolixizumab on gene and protein expression, and
explore the relationship between DNA, RNA, protein, and metabolite biomarkers
and cause, progression, and appropriate treatment of CIDP
• To assess the effect of rozanolixizumab on CIDP-specific auto-antibody levels
• To assess the effect of rozanolixizumab on vaccine antibody levels (influenza
A and tetanus)
Study design
CIDP01 is a Phase 2A, multicenter, randomized, subject-blind,
investigator-blind, placebo controlled, parallel-group study with the primary
objective of evaluating the clinical efficacy of rozanolixizumab (UCB7665) as a
treatment for subjects with chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP). Secondary objectives include evaluating the
safety and tolerability of rozanolixizumab subcutaneous (sc) infusion in
subjects with CIDP, and assessing the effect of rozanolixizumab as measured by
the total immunoglobulin G (IgG) concentrations in serum.
Intervention
Subjects will be randomized to 1 of 2 treatment arms: rozanolixizumab 10mg/kg
sc or placebo sc in a ratio of 1:1. Subjects will receive 12 weekly doses of
investigational medicinal product (IMP). The maximum duration of the study per
subject is approximately 28 weeks (up to maximum 40 weeks), consisting of a
Screening Period of between 2 and 5 weeks duration, an 11-week Treatment
Period, and an Observation Period of 12 weeks (up to 24 weeks). The study is
planned to be conducted in approximately 24 sites globally. Approximately 34
subjects will be randomized to ensure at least 30 subjects are evaluable for
the primary efficacy analysis.
All subjects completing the Treatment Period (ie, all visits performed without
relapse) will be offered the possibility to enter in the Open-Label Extension
(OLE) study, CIDP04, and be treated with rozanolixizumab. If they enter in the
OLE, Visit 17 will be the last study visit in CIDP01. If the subjects wish to
test whether they still need treatment, they will continue the Observation
Period without standard of care (SOC) treatment (ie, Ig treatment; subcutaneous
immunoglobulin [SCIg] and intravenous immunoglobulin [IVIg]). The subjects have
also the opportunity to return immediately to SOC for the duration of the
Observation Period.
Study burden and risks
The study load includes:
Visits to research doctor: 21 visits
Blood collection: 19 times
Urine sampling: 12 times
IMPD infusion (SC): 12 times
X-Thorax: 1 time
ECG: 11 times
Physical examination: 11 times
Questionnaires about the ability to perform daily and social activities, and
about signs and symptoms of tuberculosis.
The subject may experience physical or psychological discomfort with the
aforementioned tests, procedures and questionnaires.
The subject may get side effects from the study medication.
Allée de la Recherche 60
Brussels 1070
BE
Allée de la Recherche 60
Brussels 1070
BE
Listed location countries
Age
Inclusion criteria
- Subject is >= 18 years of age at Visit 1 (Screening)
- Subject has a documented definite or probable diagnosis of Chronic
Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) according to the
European Federation of Neurological Societies (EFNS)/ Peripheral Nerve Society
(PNS) criteria 2010
- Subject has an immunoglobulin-dependency confirmed by clinical examination
during therapy or upon interruption or reduction of therapy within 18 months
prior to Screening and documented in medical history
- Subject is on a stable dosage (not more than ±20% deviation) for subcutaneous
immunoglobulin (SCIg) or intravenous immunoglobulin (IVIg) and a fixed interval
for at least 4 months of either treatment
- Female subjects of childbearing potential must agree to use a highly
effective method of birth control, during the study and for a period of 3
months after their final dose of IMP
- Male subjects with a partner of childbearing potential must be willing to use
a condom when sexually active during the study and for 3 months after the final
administration of IMP
Exclusion criteria
- Previously received treatment in this study or subject has previously been
exposed to rozanolixizumab- Current diagnosis or has a history of Type 1 or
Type 2 diabetes mellitus and/or hemoglobin A1c level >6.0%
- Known immunoglobulin M (IgM)
-mediated neuropathy
- Clinical or known evidence of associated systemic diseases that might cause
neuropathy or treatment with agents that might lead to neuropathy
- History of clinically relevant ongoing chronic infections
- Family history of primary immunodeficiency
- Received a live vaccination within 8 weeks prior to the Baseline Visit; or
intends to have a live vaccination during the course of the study or within 7
weeks following the final dose of IMP
- Received any experimental biological agent within or outside of a clinical
study in the past 3 months or within 5 half-lives prior to Baseline
- Prior treatment with rituximab, ofatumumab, or ocrelizumab in the 6 months
prior to the Baseline Visit or subject has had prior treatment with rituximab,
ofatumumab, or ocrelizumab in the 12 months prior to Baseline and B cells are
not within the normal range
- Female subject who is pregnant or lactating
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 | EUCTR2016-002411-17-NL |
| ClinicalTrials.gov | NCT03861481 |
| CCMO | NL61913.018.19 |