Proof-of-concept Study for BIVV020 in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Brief description of study

Primary Objectives:

  • Part A: Efficacy of SAR445088 across three subpopulations of CIDP patients: standard of care (SOC)-Treated, SOC-Refractory and SOC-Naive
  • Part B:Long-term safety and tolerability of SAR445088 in CIDP

Secondary Objectives:

Part A:

  • Safety and tolerability of SAR445088 in CIDP
  • Immunogenicity of SAR445088
  • Efficacy of SAR445088 with overlapping SOC (SOC-Treated group)

Part B:

  • Durability of efficacy during long-term treatment with SAR445088 in CIDP
  • Long-term immunogenicity of SAR445088 in CIDP

The duration of the study for a participant will include:

Part A

  • Screening period: up to 6 weeks.
  • Treatment period: once successfully screened, enrolled participants will receive study intervention for 24 weeks.
  • Safety follow-up visit: participants who do not enroll (rollover) into Part B will be asked to attend a final safety follow-up visit that will take place 22 weeks after Week 24, ie, approximately at Week 46.

Part B

  • Treatment period (extension): for all groups, this period will consist of 52 weeks of treatment with SAR445088 (Weeks 24 to 76; Part A and B total treatment period of 76 weeks).
  • Safety follow-up visit: At the end of the Part B treatment period, participants will be asked to attend a safety follow-up visit that will take place 22 weeks after the last SAR445088 dose (Week 98).

In addition, there is a follow-up call 56 weeks ±14 days after last dose to confirm negative result of urine pregnancy test for women of childbearing potential who are participating in the study, or to query male participants regarding pregnancy of partners who are women of childbearing potential.

A follow-up telephone call at 56 weeks after last dose is included in the protocol, however the EoS has been defined as the last safety follow-up visit for the last patient which occurs at 22 weeks after last dose.

Clinical Study Identifier: NCT04658472

You may be eligible for this study if you meet the following criteria:

  • Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
  • Age: 18 Years
  • Gender: Male or Female

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
             shouldbe 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) orcorticosteroids 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
             intervention.
        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.
        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 SAR445088 or its
             components or of a severe allergic or anaphylactic reaction to any humanized or murine
             monoclonal antibody.
          -  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.
          -  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 SAR445088
             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 β-HCG blood test) or lactating females.
          -  Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen,
             anti-hepatitis B core antibodies (anti-HBc Ab)-unless anti-hepatitis B surface
             antibodies (anti-HBs Ab) are also positive , indicating natural immunity-,
             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)
        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.

Last updated on 09 May 2022

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