A Study of HyQvia and Gammagard Liquid (Kiovig) in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

• Register: ClinicalTrials.gov
• Last refreshed on: 5 June 2023
• Main ID: NCT02549170
• Date of registration: 11/09/2015
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: A Study of HyQvia and Gammagard Liquid (Kiovig) in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
• Scientific title: 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)
• Date of first enrolment: December 15, 2015
• Target sample size: 138
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02549170
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Brazil, Canada, Colombia, Croatia, Czech Republic, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Mexico, Norway, Poland, Serbia, Slovakia, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Males or females of age greater than or equal to (>=)18 years old at the time of
screening.

2. 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.

3. 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.

4. 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.

1. Screening and/or Baseline INCAT disability score of 2 (both points are from lower
extremities).

2. 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.

3. 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.

5. 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).

6. Participant is willing and able to sign an Informed Consent Form (ICF).

7. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Participants with Focal atypical CIDP or pure sensory atypical CIDP.

2. Any neuropathy of other causes, including:

1. Hereditary demyelinating neuropathies, such as hereditary sensory and motor
neuropathy (HSMN) (Charcot-Marie-Tooth [CMT] disease), and hereditary sensory and
autonomic neuropathies (HSANs).

2. 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.

3. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).

4. Multifocal motor neuropathy (MMN).

5. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.

3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high
titer antibodies to myelin-associated glycoprotein.

4. Prominent sphincter disturbance.

5. Central demyelinating disorders (eg, multiple sclerosis).

6. 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).

7. 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).

8. History of deep vein thrombosis or thromboembolic events (eg, cerebrovascular
accident, pulmonary embolism) in the past 12 months.

9. Condition(s) which could alter protein catabolism and/or IgG utilization (eg,
protein-losing enteropathies, nephrotic syndrome).

10. 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.

11. 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.

12. Clinically significant anemia or hemoglobin (Hgb) level of less than (<) 10.0 grams
per deciliter (g/dL) at screening.

13. 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.

14. Known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or
animal origin (such as bee or wasp venom)


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Intervention(s)

Biological: HYQVIA

Biological: IGIV GAMUNEX®-C

Biological: IGIV GAMMAGARD LIQUID/KIOVIG

Biological: 0.25% albumin placebo solution with rHuPH20

Primary Outcome(s)

Epoch 1: Relapse Rate [Time Frame: Week 32 End of Epoch 1 Treatment (EOET1)/Unscheduled relapse visit assessment (UV)/Early Termination (ET)]

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

Secondary Outcome(s)

Epoch 1: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS) [Time Frame: Pre-subcutaneous (SC) treatment baseline, end of Epoch 1 treatment (approximately 7.3 months)]

Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Number of Participants Who Develop Binding and/or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20) [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Number of Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs Associated With Infusions [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 2: Number of Adverse Events (AEs) Temporally Associated With Infusions [Time Frame: During an infusion or within 72 hours after completion of an infusion (up to Week 32)]

Epoch 1: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-year [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Number of Adverse Events (AEs) Temporally Associated With Infusions [Time Frame: During an infusion or within 72 hours after completion of an infusion (up to Week 32)]

Epoch 1: Number of Participants Experiencing Causally Related Serious and/or Non-Serious Adverse Events (SAEs and/or AEs) [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 2: Number of Participants Experiencing Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) [Time Frame: 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 [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 2: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality [Time Frame: 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 [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 1: Percentage of Participants Who Experience a Worsening of Functional Disability [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year [Time Frame: 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 Participant [Time Frame: 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 [Time Frame: 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 [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 2: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions [Time Frame: 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) [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 2: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Time to Relapse [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant [Time Frame: Week 32 (EOET1)/UV/ET]

Epoch 2: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

Epoch 2: Percentage of Participants With Clinically Meaningful Improvement in Functional Ability [Time Frame: Throughout Epoch 2, up to 6 months post-Epoch 1]

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) [Time Frame: 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 [Time Frame: Week 32 (EOET1)/UV/ET]

Secondary ID(s)

2014-005496-87

161403

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Development Center Americas, Inc.

Results

• Results available: Yes
• Date Posted: 24/05/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02549170