Phase III Efficacy, Safety, and Tolerability Study of HYQVIA/HyQvia and GAMMAGARD LIQUID/KIOVIG in CIDP
This is a Phase III, prospective, multicenter study with two study parts (epochs) to evaluate the efficacy, safety, and tolerability of HYQVIA/HyQvia (IGI, 10% with recombinant human hyaluronidase (rHuPH20) administered subcutaneously) for maintenance therapy to prevent relapse (Epoch 1) and GAMMAGARD LIQUID/KIOVIG (immunoglobulin G intravenous (IGIV) 10% administered intravenously) for the treatment of CIDP (Epoch 2). This study will enroll adult subjects with a confirmed diagnosis of CIDP and who have remained on a stable dosing regimen (monthly equivalent dose of 0.4 to 2.4 g/kg body weight (BW) with a dosing interval of 2 to 6 weeks) of IGIV therapy for at least 3 months prior to screening. In this double-blind, placebo-controlled phase of the study (Epoch 1), eligible subjects will be randomized in a 1:1 ratio to receive either HYQVIA/HyQvia or 0.25% albumin placebo solution with rHuPH20 every two, three, or four weeks in a double-blind fashion for a period of 6 months or until relapse. Subjects who relapse during Epoch 1 will enter Epoch 2 to receive IGIV treatment for a period of 6 months.
- Chronic Inflammatory Demyelinating Polyradiculoneuropathy
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Males or females of age greater than or equal to (>=)18 years old at the time of screening.
- Documented diagnosis of definite or probable Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (focal atypical CIDP and pure sensory atypical CIDP will be excluded) consistent with EFNS/PNS 2010 criteria (European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy, 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.
- 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 amyloidosisc.Multifocal motor neuropathy (MMN).
- 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) > 2.5x upper limit of normal (ULN)
- Platelet count <100,000 cells per micro liter (cells/µL).
- Absolute neutrophil count (ANC) <1000 cells/µL.
- 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.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Triple (Participant, Care Provider, Investigator)
Epoch 1: HYQVIA/HyQvia
|Participants will receive SC HYQVIA/HyQvia at a dose of 80 Unit per gram (U/g) immunoglobulin (IgG) which will be same as the participants pre-randomization monthly equivalent IgG dose (or at matching infusion volume for participants in the placebo group) when administered at a dosing frequency of every 2, 3, or 4 weeks for 6 months or until relapse.||
Epoch 1: Placebo with rHuPH20
|Participants will receive sequential 0.25% albumin placebo with rHuPH20 at a dose of 80U/g IgG subcutaneously for 6 months or until relapse. Dosing regimen for placebo treatment will be the same as the participant's pre-randomization monthly equivalent IgG infusion volume when administered every 2, 3, or 4 weeks.||
Epoch 2: IGIV
|Participants will recieve an induction dose of 2 Gram per kilogram (g/kg) Intravenous immunoglobulin G (IGIV), followed by maintenance infusions at the same monthly dose as the participant's pre-randomization IgG dose, every 3 weeks for 6 months or until relapse.||
- Baxalta now part of Shire
Study ContactShire Contact
+1 866 842 5335