Proof-of-concept study for BIVV020 in chronic inflammatory demyelinating polyneuropathy (CIDP)

Phase 1

Active, not recruiting

• Conditions: Chronic inflammatory demyelinatingpolyneuropathy; MedDRA version: 20.0Level: LLTClassification code 10077384Term: Chronic inflammatory demyelinating polyneuropathySystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-004006-54-FR
• Lead Sponsor: Sanofi-Aventis Recherche & Développement

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-23
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 90

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
judgement.
Or
- 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 patho

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
antibody.
- Presence of conditions (medical history or laboratory assessments) that may
predispose the participant to excessive bleeding or increased risk of infection.
- 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
transplantation.
- 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 ß-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
antibodies).
- Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and
CNTN1).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified