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

Related Clinical Trial
Immunoadsorption Versus Immunoglobulins for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Hizentra® in Inflammatory Neuropathies – pHeNIx Study Proof-of-concept Study for BIVV020 in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Subcutaneous Immunoglobulin in De-novo CIDP (SIDEC) InertiaLocoGraphy as a Biomarker of Immunoglobulin Therapy Efficacy in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy: A Phase II Study Randomized Open-label Trial to Compare Efficacy and Tolerance of Corticosteroids and IVIg Study to Evaluate Safety and Efficacy of Three Different Dosages of NewGam in Patients With Chronic Inflammatory Demyelinating Poly (Radiculo) Neuropathy A Registered Cohort Study of Immune-Mediated Neuropathies Interest of Mycophenolate for CIDP Weaning Efficacy and Safety Study of I10E in Treatment of Patients With CIDP Transcriptome Analysis of the Peripheral Blood in CIDP Phase III Efficacy, Safety, and Tolerability Study of HYQVIA/HyQvia and GAMMAGARD LIQUID/KIOVIG in CIDP Safety and Efficacy Study of Three Different Dosages of NewGam in Patients With CIDP Efficacy and Safety Study of I10E in the Maintenance Treatment of Patients With CIDP: Extension of PRISM Study I10E-1302 Evaluating the Effectiveness of Telemonitoring System in the Management of Patients With CIDP Subcutaneous Immunoglobulin for CIDP Long-Term Tolerability and Safety of HYQVIA/HyQvia in CIDP The Evaluation of Efficacy and Safety of Rituximab in Refractory CIDP Patients With IgG4 Autoantibodies Single vs. Multiple Privigen Dose Regimens in Pediatric CIDP Hematopoietic Stem Cell Transplantation in Chronic Inflammatory Demyelinating Polyneuropathy Lipoic Acid to Treat Chronic Inflammatory Demyelinating Polyneuropathy MRI in Diagnosing and Monitoring CIDP High-dose Cyclophosphamide for Moderate to Severe Refractory Chronic Inflammatory Demyelinating Polyneuropathy Biomark Study: Predict Intravenous Immunoglobulin Responders in Chronic Inflammatory Demyelinating Polyradiculoneuropathy A Study to Assess the Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP, an Autoimmune Disorder That Affects the Peripheral Nerves) Phase III Clinical Trial of NPB-01maintenance Therapy in Patients With Chronic Inflammatory Demyelinating Polyneuropathy. IVIg Treatment-Related Fluctuations in CIDP Patients Using Daily Grip Strength Measurements A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP, an Autoimmune Disorder That Affects the Peripheral Nerves) Safety and Efficacy of Avonex in Subjects With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) Evaluate Efficacy and Safety of Fingolimod 0.5 mg Orally Once Daily Versus Placebo in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients. Prevalence of Decreased Corneal Sensation in Patients With Chronic Inflammatory Demyelinating Polyneuropathy Panzyga in CIDP Administered at Different Infusion Rates Study of Efficacy and Safety of Privigen in Subjects With Chronic Inflammatory Demyelinating Polyneuropathy Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Treatment With Subcutaneous Immunoglobulin (IgPro20) A Study to Assess Long-term Safety, Tolerability and Efficacy of Rozanolixizumab in Subjects With Chronic Inflammatory Demyelinating Polyradiculoneuropathy A Study to Assess the Efficacy, Safety and Tolerability of Rozanolixizumab in Subjects With Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Brief Title

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

Official Title

A Phase 2, Multicenter, Open-label, Proof-of-concept Study Evaluating the Efficacy, Safety, and Tolerability of BIVV020 in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Brief Summary

      Primary Objective:

        -  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

      Secondary Objective:

      -Part A: 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
    

Detailed Description

      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 BIVV020 (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 BIVV020 dose
      (Week 98).
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Part A, SOC-Treated: Percentage of participants relapsing after withdrawal of SOC and during the BIVV020 treatment period

Secondary Outcome

 Part A: Number of participants reported with adverse events

Condition

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Intervention

BIVV020

Study Arms / Comparison Groups

 SOC-Treated
Description:  Part A: Eligible participants will receive BIVV020 for 24 weeks. Weeks 1-12 (overlap period): Participants will be administered BIVV020 with superimposing effects of standard of care (SOC) therapy; Weeks 13-24: BIVV020 administration.
Participants who do not enroll into Part B will be asked to attend a final safety follow-up visit that will take place 22 weeks after Week 24 (approximately at Week 46).
Part B: Participants who successfully complete Part A, will be reassessed for continuing eligibility and will be given the option of rolling into Part B, where they will continue receiving BIVV020 for an additional 52 weeks. 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 BIVV020 dose (at approximately week 98).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

90

Start Date

April 2021

Completion Date

May 2024

Primary Completion Date

May 2024

Eligibility Criteria

        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 Protocol Registration Form Page 5 of 12 Property of the Sanofi Group - strictly
             confidential Version number: 1.0, dated 27-mar-2020 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
             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 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 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 antibodies).

          -  Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and CNTN1)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clinical Sciences & Operations, 800-633-1610, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT04658472

Organization ID

PDY16744

Secondary IDs

2020-004006-54

Responsible Party

Sponsor

Study Sponsor

Sanofi


Study Sponsor

Clinical Sciences & Operations, Study Director, Sanofi


Verification Date

March 2021