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临床试验/NCT02549170
NCT02549170已完成3 期

A Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) and Immune Globulin Infusion (Human), 10% (GAMMAGARD LIQUID/KIOVIG) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Baxalta now part of Shire164 个研究点 分布在 13 个国家目标入组 138 人开始时间: 2015年12月15日最近更新:
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适应症

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
138
试验地点
164
主要终点
Epoch 1: Relapse Rate
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The aim of this study is to learn more about the following treatment options in adults with CIDP:

  • Subcutaneous self-infusion with HyQvia.
  • Intravenous infusion with Gammagard/Kiovig. Gammagard and Kiovig are the brand names for the same immunoglobulin compound.

The study is in two parts. In Part 1, participants receive either HyQvia or a placebo subcutaneously. In Part 2 (only for participants who have a CIPD relapse during Part 1), participants will receive Gammagard Liquid/Kiovig intravenously. US participants will receive Gamunex-C.

The first SC infusion will be given in the study clinic. The remaining SC infusions may be given in the study clinic or the participant's home. This will be decided by the study doctor and whether the participant or their caregiver can do the self-infusion.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Triple (Participant, Care Provider, Investigator)

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Males or females of age greater than or equal to (>=)18 years old at the time of screening.
  • •Participant has a documented diagnosis of definite or probable Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (focal atypical CIDP and pure sensory atypical CIDP will be excluded), as confirmed by a neurologist specializing/experienced in neuromuscular diseases to be consistent with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 criteria (European Federation of Neurological Societies, 2010). Fulfillment of electrodiagnostic criteria must be confirmed by an independent qualified/experienced central reader.
  • •Participant has responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 gram per kilogram (g/kg) BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of IGIV treatment must be between 2 and 6 weeks (inclusive). Variations in the dosing interval of up to ± 7 days or monthly dose amount of up to ± 20% between participant's pre-study Immunoglobulin G (IgG) infusions are within acceptable limits.
  • •INCAT disability score between 0 and 7 (inclusive). Participants with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater documented in the medical record. Participants will be eligible if one of the below eligibility criteria are met:
  • •Screening and Baseline INCAT disability score of between 3 and 7 inclusive.
  • •Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities).
  • •Screening and/or Baseline INCAT disability score of 2 (both points are not from lower extremities) AND has at least a score of 2 or greater documented in the medical record prior to screening. If a score was greater than 2 documented in the medical record prior to screening at least 2 points must be from lower extremities.
  • •Screening and/or Baseline INCAT disability score of 0 or 1 AND has at least a score of 2 or greater (both from lower extremities) documented in the medical record prior to screening, at least 2 points must be from lower extremities.
  • •If female of childbearing potential, the participant must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of investigational product (IP).
  • •Participant is willing and able to sign an Informed Consent Form (ICF).
  • •Participant is willing and able to comply with the requirements of the protocol.

排除标准

  • •Participants with Focal atypical CIDP or pure sensory atypical CIDP.
  • •Any neuropathy of other causes, including:
  • •Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth [CMT] disease), and hereditary sensory and autonomic neuropathies (HSANs).
  • •Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy, lymphoma, and amyloidosis.
  • •Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).
  • •Multifocal motor neuropathy (MMN).
  • •Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.
  • •Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.
  • •Prominent sphincter disturbance.
  • •Central demyelinating disorders (eg, multiple sclerosis).
  • •Any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of CIDP or outcome measures (eg, arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy) (Participants with clinically diagnosed diabetes mellitus who do not have diabetic peripheral neuropathy, who have adequate glycemic control with Hemoglobin A1C; also known as glycosylated or glycated hemoglobin (HbA1C) of less than (<) 7.5% at screening, and who agree to maintain adequate glycemic control during the study are allowed).
  • •Congestive heart failure (New York Heart Association [NYHA] Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (ie, diastolic blood pressure greater than (>) 100 millimeter of mercury (mmHg) and/or systolic blood pressure >160 mmHg).
  • •History of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) in the past 12 months.
  • •Condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome).
  • •Known history of chronic kidney disease, or glomerular filtration rate (GFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) estimated based on CKD-EPI equation (Levey et al., 2009) at the time of screening.
  • •Participant with active malignancy requiring chemotherapy and/or radiotherapy, or history of malignancy with less than 2 years of complete remission prior to screening. Exceptions are: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment.
  • •Clinically significant anemia or hemoglobin (Hgb) level of less than (<) 10.0 grams per deciliter (g/dL) at screening.
  • •Hypersensitivity or adverse reactions (AR's) (eg, urticaria, breathing difficulty, severe hypotension, or anaphylaxis) to human blood products such as human IgG, albumin, or other blood components.
  • •Known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin (such as bee or wasp venom).
  • •Known history of or immunoglobulin A (IgA) deficiency (<8 milligram per deciliter [mg/dL]) at screening.
  • •Abnormal laboratory values at screening:
  • •Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5* upper limit of normal (ULN)
  • •Platelet count <100,000 cells per microliter (cells/mcL).
  • •Absolute neutrophil count (ANC) <1000 cells/mcL.
  • •Ongoing/active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1/2 infection.
  • •The participant has received or is currently receiving treatment with immunomodulatory/ immunosuppressive agents within 6 months prior to screening.
  • •Participant has received or is currently receiving treatment with corticosteroids dose within 8 weeks prior to screening, regardless of indication.
  • •Participant has undergone plasma exchange (PE) within 3 months prior to screening.
  • •The participant has any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study.
  • •The participant is nursing or intends to begin nursing during the course of the study.
  • •Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study (with the exception of the HYQVIA/HyQvia extension study in CIDP) involving an IP or investigational device during the course of this study.
  • •The participant is a family member or employee of the investigator.
  • •Participants with acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of develop thrombotic events. Examples include:
  • •a. Hereditary Thrombophilias i. Factor V Leiden mutation. ii. Prothrombin 20210A mutation. iii. Protein C deficiency. iv. Protein S deficiency. v. Antithrombin deficiency. b. Acquired thrombophilias i. Antiphospholipid antibody syndrome. ii. Activated protein C Resistance acquired. iii. Homocystinemia.

结局指标

主要结局

Epoch 1: Relapse Rate

时间窗: Week 32 End of Epoch 1 Treatment (EOET1)/Unscheduled relapse visit assessment (UV)/Early Termination (ET)

Relapse rate is defined as the percentage of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of \>=1 point relative to the pre- subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

Epoch 2: Responder Rate

时间窗: Up to 6 Months post-Epoch 1 (End of Epoch 2 Treatment [EOE2T])/Unscheduled visit assessment (UV)/Early Termination

Responder rate is defined as clinically meaningful improvement in functional ability defined as a decrease of \>=1 point in the adjusted INCAT disability score at the completion of the intravenous (IV) treatment period \[6 months\] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.

次要结局

  • Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS)(Pre-subcutaneous (SC) treatment baseline, end of Epoch 1 treatment (approximately 7.3 months))
  • Epoch 1: Percentage of Participants Who Experience a Worsening of Functional Disability(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions(Week 32 (EOET1)/UV/ET)
  • Time to Relapse(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Participants Experiencing Causally Related Serious and/or Non-Serious Adverse Events (SAEs and/or AEs)(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Infusions in Participants for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs)(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs Associated With Infusions(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Number of Participants Who Develop Binding and/or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)(Week 32 (EOET1)/UV/ET)
  • Epoch 2: Number of Adverse Events (AEs) Temporally Associated With Infusions(During an infusion or within 72 hours after completion of an infusion (up to Week 32))
  • Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 1: Number of Adverse Events (AEs) Temporally Associated With Infusions(During an infusion or within 72 hours after completion of an infusion (up to Week 32))
  • Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant(Week 32 (EOET1)/UV/ET)
  • Epoch 2: Number of Participants Experiencing Any Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 1: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion(Week 32 (EOET1)/UV/ET)
  • Epoch 2: Number of Participants Experiencing Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs)(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Participant(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-year(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Participant(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year(Week 32 (EOET1)/UV/ET)
  • Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Infusion(Week 32 (EOET1)/UV/ET)
  • Epoch 2: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs Associated With Infusions(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or Adverse Events (AEs)(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected Ars, Expressed as Number of Events Per Infusion(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant(Throughout Epoch 2, up to 6 months post-Epoch 1)
  • Epoch 2: Percentage of Participants With Clinically Meaningful Improvement in Functional Ability(Throughout Epoch 2, up to 6 months post-Epoch 1)

研究者

发起方
Baxalta now part of Shire
申办方类型
Industry
责任方
Sponsor

研究点 (164)

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