|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|Chronic inflammatory demyelinating
|E.1.1.1||Medical condition in easily understood language ||
|E.1.1.2||Therapeutic area ||Diseases [C] - Nervous System Diseases [C10]
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10077384
|E.1.2||Term ||Chronic inflammatory demyelinating polyneuropathy
|E.1.2||System Organ Class ||100000004852
|E.1.3||Condition being studied is a rare disease || No
|E.2 Objective of the trial
|E.2.1||Main objective of the trial ||
|- Part A: Efficacy of BIVV020 across three subpopulations of CIDP patients: standard of care
(SOC)-Treated, SOC-Refractory and SOC-Naive
- Part B:Long-term safety and tolerability of BIVV020 in CIDP
|E.2.2||Secondary objectives of the trial ||
- Safety and tolerability of BIVV020 in CIDP
- Immunogenicity of BIVV020
- Efficacy of BIVV020 with overlapping SOC (SOC-Treated group)
• Part B:
- Durability of efficacy during long-term treatment with BIVV020 in CIDP
- Long-term immunogenicity of BIVV020 in CIDP
|E.2.3||Trial contains a sub-study || No
|E.3||Principal inclusion criteria ||
|- Adults ≥18 years of age at the time of signing the informed consent.
- Documented definite or probable diagnosis of CIDP (typical CIDP, pure motor
CIDP, or Lewis-Sumner Syndrome) according to the European Federation of Neurological
Societies (EFNS)/Peripheral Nerve Society (PNS) Task Force first revision.
- Belonging to one of the following three groups: standard-of-care (SOC)-Treated,
SOC-Refractory or SOC-Naïve, as defined below.
- SOC-Treated (all criteria a-c must be met): a) Documented evidence of
objective response to SOC, with clinically meaningful improvement. Clinically meaningful
improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT
score, ≥4 points increase in RODS total score, ≥3 points increase in MRC Sum score, ≥8
kilopascal improvement in mean grip strength (one hand), or an equivalent improvement
based on information documented in medical records and per the PI’s judgement. b) Must
be on stable SOC therapy, defined as no change greater than 10% in frequency or dose
of immunoglobulin therapy or corticosteroids within 8 weeks prior to screening, remaining
at stable SOC therapy until the time of first BIVV020 dosing. c) Evidence of clinically
meaningful deterioration on interruption or dose reduction of SOC therapy within 24
months prior to screening, determined by clinical examination or medical records.
Clinically meaningful deterioration is defined as one of the following: ≥1-point increase in
adjusted INCAT score, decrease in RODS total score ≥4 points, decrease in MRC Sum
score ≥3, mean grip strength worsening of ≥8 kilopascals (one hand), or an equivalent
deterioration based on information from medical records and at the PI’s judgement.
- SOC-Refractory (all criteria a-d must be met): a) Evidence of failure or
inadequate response to SOC defined as no clinically meaningful improvement and
persistent INCAT score ≥2 after treatment for a minimum of 12 weeks on SOC prior to
screening. A clinically meaningful improvement is defined as one of the following: ≥1-point
decrease in adjusted INCAT score, increase in RODS total score ≥4 points, increase in
MRC Sum score ≥3, mean grip strength improvement of ≥8 kilopascals (one hand), or
equivalent improvement based on information from medical records and at the PI’s
- Unable to receive or continue treatment with immunoglobulins or corticosteroids
due to side effects.
- b) Patient has not received immunoglobulins (IVIg or SCIg) within 12 weeks
prior to screening. c) Certain immunosuppressant drugs are allowed in this group if taken
for ≥6 months and at a stable dose for ≥3 months prior to screening: azathioprine,
methotrexate, mycophenolate mofetil and cyclosporine. Oral corticosteroids are allowed if on a stable dose of <20 mg/day of prednisone (or equivalent dose for other oral
corticosteroids) for ≥3 months prior to screening. d) INCAT score: 2-9 (a score of 2 should
be exclusively from leg disability component of INCAT).
- SOC-Naïve (all criteria a-c must be met): a) Participants without previous
treatment for CIDP or participants who received immunoglobulins (IVIg or SCIg) or
corticosteroids but were stopped for reasons other than lack of response or side effects.
b) Not treated with immunoglobulins (IVIg or SCIg) or corticosteroids for at least 6 months
prior to screening. c) INCAT score: 2-9 (a score of 2 should be exclusively from leg
disability component of INCAT.
- Documented vaccinations against encapsulated bacterial pathogens given
within 5 years of enrollment or initiated a minimum of 14 days prior to first dose
- A female participant must use a double contraception method including a highly
effective method of birth control from inclusion and up to 52 weeks plus 30 days after the
last study dose and agree not to donate eggs, ova or oocytes during this period.
- A female participant must have a negative highly sensitive pregnancy test (urine
or serum) as required by local regulations within 24 hours before the first dose of study
- Male participants, whose partners are of childbearing potential must accept to
use, during sexual intercourse, a double contraceptive method according to the following:
condom plus an additional highly effective contraception
- Male participants must have agreed not to donate sperm during the intervention
and up to 52 weeks after the last dose.
- Capable of giving signed informed consent
|E.4||Principal exclusion criteria||
|- Polyneuropathy of other causes, including but not limited to hereditary
demyelinating neuropathies, neuropathies secondary to infection or systemic disease,
diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy,
monoclonal gammopathy of uncertain significance, lumbosacral radiculoplexus
neuropathy, pure sensory CIDP and acquired demyelinating symmetric (DADS)
neuropathy (also known as distal CIDP).
- Any other neurological or systemic disease that can cause symptoms and signs
interfering with treatment or outcome assessments.
- Poorly controlled diabetes (HbA1c >7%).
- Serious infections requiring hospitalization within 30 days prior to screening and
any active infection requiring treatment during screening.
- Clinical diagnosis of SLE.
- Sensitivity to any of the study interventions, or components thereof, or drug or
other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to BIVV020 or its components
or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal
- Participants with a history of suicidality in the six months prior to screening or currently at risk of committing suicide.
- Presence of conditions (medical history or laboratory assessments) that may
predispose the participant to excessive bleeding or increased risk of infection.
- Evidence of CIDP relapse within 6 weeks after receiving a vaccination.
- A history of CIDP relapse after prior vaccination.
- Recent or planned major surgery that could confound the results of the trial or
put the participant at undue risk.
- Treatment with plasma exchange within 12 weeks prior to screening.
- Prior treatment with rituximab or ocrelizumab in the 6 months prior to BIVV020
dosing or until return of B-cell counts to normal levels, whichever is longer.
- Immunosuppressive/chemotherapeutic medications such as azathioprine,
methotrexate, cyclophosphamide, cyclosporine, mycophenolate mofetil, tacrolimus,
interferon, TNF-alpha inhibitor: within 6 months prior to dosing (except for some cases as
indicated in the SOC-Refractory group).
- Treatment (any time) with highly immunosuppressive/chemotherapeutic
medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine.
- Treatment (any time) with total lymphoid irradiation or bone marrow
- Use of any specific complement system inhibitor (eg, eculizumab) within 12
weeks or 5 times the half-life of the product, whichever is longer, prior to screening.
- Pregnant (defined as positive β-HCG blood test) or lactating females.
- Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen,
antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies,
anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2
- Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and
|E.5 End points
|E.5.1||Primary end point(s)||
|1) Part A, SOC-Treated: Percentage of
participants relapsing after withdrawal of SOC
and during the BIVV020 treatment period:
Relapse will be defined as ≥1-point increase in adjusted Inflammatory
neuropathy cause and treatment (INCAT) disability score.
2) Part A, SOC-Refractory and SOC-Naïve:
Percentage of participants responding during
the BIVV020 treatment period: Response will be defined as ≥1-point decrease in adjusted INCAT disability
3)Part B: Number of participants reported with
adverse Events:Number of participants reported with adverse events during 76 weeks of
treatment and 22 weeks of follow-up.
|E.5.1.1||Timepoint(s) of evaluation of this end point||
|1)Day 1 up to 24 weeks
2) Day 1 up to 24 weeks
3) Day 1 up to Week 98
|E.5.2||Secondary end point(s)||
|1)Part A: Number of participants reported with
adverse Events:Number of participants reported with adverse events during 24 weeks of
treatment period and if not enrolled to Part B, 22 weeks of follow-up period.
2)Part A: Number of participants with incidence
and titer of anti-BIVV020 antibodies (ADA):Incidence and titer of anti-BIVV020 antibodies (ADA) will be assessed during the 24 weeks of treatment period and if not enrolled to Part B, 22 weeks of follow-up period.
3)Part A: Percentage of participants in the SOC Treated
group improving during the overlap treatment period: Improvement will be defined as ≥1 point decrease in adjusted INCAT
4)Part B, SOC-Treated: Percentage of
participants relapse-free during the treatment
extension period:Relapse-free will be defined as no increase in adjusted INCAT disability
score >2 points.
5)Part B, SOC-Refractory and SOC-Naive:
Percentage of participants with sustained
response during the treatment extension period:Maintenance of response will be defined as no increase in adjusted INCAT
disability score >2 points.
6)Part B: Long-term immunogenicity:Incidence and titer of anti-BIVV020 antibodies during the entire BIVV020
treatment period and follow-up period.
|E.5.2.1||Timepoint(s) of evaluation of this end point||
|1)-2) Day 1 up to 46 weeks
3)Day 1 up to 12 weeks
4)-5)Week 24 up to Week 76
6)Day 1 Up to Week 98
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| No
|E.6.13.1||Other scope of the trial description||
|E.7||Trial type and phase
|E.7.1||Human pharmacology (Phase I)|| No
|E.7.1.1||First administration to humans|| No
|E.7.1.2||Bioequivalence study|| No
|E.220.127.116.11||Other trial type description||
|E.7.2||Therapeutic exploratory (Phase II)|| Yes
|E.7.3||Therapeutic confirmatory (Phase III)|| No
|E.7.4||Therapeutic use (Phase IV)|| No
|E.8 Design of the trial
|E.8.1.3||Single blind|| No
|E.8.1.4||Double blind || No
|E.8.1.5||Parallel group|| No
|E.8.1.6||Cross over || No
|E.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || No
|E.8.2.4||Number of treatment arms in the trial||1
The trial involves single site in the Member State concerned
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes
|E.8.4.1||Number of sites anticipated in Member State concerned||2
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.5.1||Number of sites anticipated in the EEA||17
|E.8.6 Trial involving sites outside the EEA
|E.8.6.1||Trial being conducted both within and outside the EEA|| Yes
|E.8.6.2||Trial being conducted completely outside of the EEA|| No
|E.8.6.3||If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned||
|E.8.7||Trial has a data monitoring committee|| No
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|E.8.9.1||In the Member State concerned years||3
|E.8.9.1||In the Member State concerned months||
|E.8.9.1||In the Member State concerned days||17
|E.8.9.2||In all countries concerned by the trial years||3
|E.8.9.2||In all countries concerned by the trial days||17