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

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ClinicalTrials.gov Identifier: NCT04658472
Recruitment Status : Recruiting
First Posted : December 8, 2020
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Bioverativ, a Sanofi company )

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


Condition or disease Intervention/treatment Phase
Chronic Inflammatory Demyelinating Polyradiculoneuropathy Drug: BIVV020 Phase 2

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).

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 28, 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
Experimental: SOC-Treated

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).

Drug: BIVV020
Pharmaceutical form:Solution for Injection

Experimental: SOC-Refractory

Part A: Eligible participants will receive BIVV020 for 24 weeks.

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 (approximately week 98).

Drug: BIVV020
Pharmaceutical form:Solution for Injection

Experimental: SOC-Naive

Part A: Eligible participants will receive BIVV020 for 24 weeks.

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 (approximately week 98).

Drug: BIVV020
Pharmaceutical form:Solution for Injection




Primary Outcome Measures :
  1. Part A, SOC-Treated: Percentage of participants relapsing after withdrawal of SOC and during the BIVV020 treatment period [ Time Frame: Day 1 up to 24 weeks ]
    Relapse will be defined as ≥1-point increase in adjusted Inflammatory neuropathy cause and treatment (INCAT) disability score. The Investigator/rater will evaluate the level of impairment in participants' arms and legs each on a scale of 0 (least impaired) to 5 (most impaired), in the context of a neurological examination, and will record the added scores (range 0 to 10) per the INCAT reporting instructions. A low score reflects no or minimal disability eg, no arm dysfunction or walking normally, whereas higher scores indicate more disability eg, wheelchair bound or no purposeful arm movement.

  2. Part A, SOC-Refractory and SOC-Naïve: Percentage of participants responding during the BIVV020 treatment period [ Time Frame: Day 1 up to 24 weeks ]
    Response will be defined as ≥1-point decrease in adjusted INCAT disability score. The Investigator/rater will evaluate the level of impairment in participants' arms and legs each on a scale of 0 (least impaired) to 5 (most impaired), in the context of a neurological examination, and will record the added scores (range 0 to 10) per the INCAT reporting instructions. A low score reflects no or minimal disability eg, no arm dysfunction or walking normally, whereas higher scores indicate more disability eg, wheelchair bound or no purposeful arm movement.

  3. Part B: Number of participants reported with adverse events [ Time Frame: Day 1 up to Week 98 ]
    Number of participants reported with adverse events during 76 weeks of treatment and 22 weeks of follow-up.


Secondary Outcome Measures :
  1. Part A: Number of participants reported with adverse events [ Time Frame: Day 1 up to 46 Weeks ]
    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) [ Time Frame: Day 1 up to 46 Weeks ]
    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 [ Time Frame: Day 1 up to 12 Weeks ]
    Improvement will be defined as ≥1 point decrease in adjusted INCAT disability score. The Investigator/rater will evaluate the level of impairment in participants' arms and legs each on a scale of 0 (least impaired) to 5 (most impaired), in the context of a neurological examination, and will record the added scores (range 0 to 10) per the INCAT reporting instructions. A low score reflects no or minimal disability eg, no arm dysfunction or walking normally, whereas higher scores indicate more disability eg, wheelchair bound or no purposeful arm movement.

  4. Part B, SOC-Treated: Percentage of participants relapse-free during the treatment extension period [ Time Frame: Week 24 up to Week 76 ]
    Relapse-free will be defined as no increase in adjusted INCAT disability score greater than or equal to 2 points. The Investigator/rater will evaluate the level of impairment in participants' arms and legs each on a scale of 0 (least impaired) to 5 (most impaired), in the context of a neurological examination, and will record the added scores (range 0 to 10) per the INCAT reporting instructions. A low score reflects no or minimal disability eg, no arm dysfunction or walking normally, whereas higher scores indicate more disability eg, wheelchair bound or no purposeful arm movement.

  5. Part B, SOC-Refractory and SOC-Naive: Percentage of participants with sustained response during the treatment extension period [ Time Frame: Week 24 up to Week 76 ]
    Maintenance of response will be defined as no increase in adjusted INCAT disability score greater than or equal to 2 points. The Investigator/rater will evaluate the level of impairment in participants' arms and legs each on a scale of 0 (least impaired) to 5 (most impaired), in the context of a neurological examination, and will record the added scores (range 0 to 10) per the INCAT reporting instructions. A low score reflects no or minimal disability eg, no arm dysfunction or walking normally, whereas higher scores indicate more disability eg, wheelchair bound or no purposeful arm movement.

  6. Part B: Long-term immunogenicity [ Time Frame: Day 1 Up to Week 98 ]
    Incidence and titer of anti-BIVV020 antibodies during the entire BIVV020 treatment period and follow-up period.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04658472


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, California
Investigational Site Number 8400002 Recruiting
Orange, California, United States, 92868
United States, Florida
Investigational Site Number 8400001 Recruiting
Tampa, Florida, United States, 33612-6601
Canada
Investigational Site Number 1240001 Recruiting
Gatineau, Canada, J8Y 1W2
China
Investigational Site Number 1560001 Recruiting
Shanghai, China, 200040
Investigational Site Number 1560004 Recruiting
Wuhan, China, 430030
Netherlands
Investigational Site Number 5280002 Recruiting
Utrecht, Netherlands, 3584 CX
Spain
Investigational Site Number 7240002 Recruiting
Barcelona, Spain, 08035
Investigational Site Number 7240003 Recruiting
Valencia, Spain, 46026
Sponsors and Collaborators
Bioverativ, a Sanofi company
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Bioverativ, a Sanofi company
ClinicalTrials.gov Identifier: NCT04658472    
Other Study ID Numbers: PDY16744
2020-004006-54 ( EudraCT Number )
U1111-1246-7023 ( Other Identifier: UTN )
First Posted: December 8, 2020    Key Record Dates
Last Update Posted: July 1, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polyneuropathies
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Polyradiculoneuropathy
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases