E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic inflammatory demyelinating polyradiculoneuropathy |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Inflammatory Demyelinating Polyneuropathy is a rare disorder of the peripheral nerves (nerves outside the central nervous system) caused by damage to the covering of the nerves, called myelin. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057645 |
E.1.2 | Term | Chronic inflammatory demyelinating polyradiculoneuropathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Epoch 1:SC Treatment Period
1.To evaluate the efficacy of HyQvia as a maintenance therapy for CIDP to prevent relapse of neuromuscular disability and impairment.
Epoch 2: IV Treatment Period
1.To evaluate the efficacy of KIOVIG for the treatment of CIDP to improve neuromuscular disability and impairment. |
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E.2.2 | Secondary objectives of the trial |
Epoch 1:SC Treatment Period
1. To assess the time to CIDP relapse during maintenance therapy with HyQvia, compared to placebo.
2. To assess the effect of HyQvia on activities of daily living (ADL).
3. To assess the safety and tolerability of HyQvia.
4. To monitor for the presence of binding and neutralizing anti-rHuPH20 antibodies following HyQvia administration.
Epoch 2: IV Treatment Period
1. To assess the safety and tolerability of KIOVIG.
2. To assess the effect of GAMMAGARD LIQUID/KIOVIG on activities of daily living. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females of age ≥18 years old at the time of screening.
2. Subject has a documented diagnosis of definite or probable CIDP (focal atypical CIDP and pure sensory atypical CIDP will be excluded).
3. Subject 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 g/kg BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of IGIV treatment must be between 2 to 6 weeks (inclusive). Variations in the dosing interval of up to ±7 days or monthly dose amount of up to ±20% between subject's pre study IgG infusions are within acceptable limits.
4. INCAT disability score between 0 to 7 (inclusive). Subjects 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. Subjects will be eligible if one of the below eligibility criteria are met:
a. Screening and Baseline INCAT disability score of between 3 and 7 inclusive.
b. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities)
c. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities) AND has at least a score of 2 or greater documented in the clinical 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.
d. Screening and/or Baseline INCAT disability score of 0 and 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 subject 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.
6. Subject is willing and able to sign an Informed Consent Form (ICF).
7. Subject is willing and able to comply with the requirements of the protocol. |
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E.4 | Principal exclusion criteria |
1.Subjects with focal atypical CIDP or pure sensory atypical CIDP.
2. Any neuropathy of other causes, including:
a. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (Charcot-Marie-Tooth [CMT] disease), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), and hereditary sensory and autonomic neuropathies.
b. 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
c. Multifocal motor neuropathy
d. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy
3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titre antibodies to myelin-associated glycoprotein.
4. Presence of prominent sphincter disturbance.
5. Any central demyelinating disorders such as 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, including (but not limited to) arthritis, stroke, and Parkinson’s disease and diabetic peripheral neuropathy.
7. The subject has received or is currently receiving treatment with immunomodulatory/immunosuppressive agents within 6 months prior to screening.
8. The subject has received or is currently receiving treatment with corticosteroids within 3 months prior to screening. The following exceptions for prednisolone or its equivalent are allowed: stable dosages of low-dose systemic corticosteroids (≤10 mg prednisolone/day or its equivalent) and non-systemic corticosteroids (topical, ophthalmic, or inhaled glucocorticoids). In addition and for the purpose of treating AE or non-CIDP intercurrent disease, a single corticosteroid dose >10 mg prednisolone or a single short-term course of ≤ to 7 days (such as Methylprednisolone Dose Pack) within 3 months prior to screening is allowed.
9. The subject has undergone plasma exchange within 3 months prior to screening.
10. The subject has any disorder or condition that in the investigator’s judgment may impede the subject’s participation in the study, pose increased risk to the subject, or confound the results of the study.
11. The subject is nursing or intends to begin nursing during the course of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Epoch 1: SC Treatment Period
Relapse rate
Epoch 2: IV Treatment Period
Responder rate
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Epoch 1: SC Treatment Period
up to 6 months
Epoch 2: IV Treatment Period
up to 6 months |
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E.5.2 | Secondary end point(s) |
Epoch 1: SC Treatment Period
Efficacy
Proportion of subjects who experience a worsening of functional disability defined as an increase of ≥1 point relative to the pre-SC treatment baseline score in 2 consecutive adjusted INCAT disability scores OR who experience CIDP worsening (defined as a ≥8 kPa decrease in the hand grip strength in the more affected hand) OR ≥4 points decrease in R-ODS relative to the pre-SC treatment baseline score at 2 consecutive time points (at the time of withdrawal from the SC treatment period)
2.Time to relapse
3.Change from pre-SC treatment baseline in R-ODS score
Safety
Number (%) of subjects with AE's
Number (%) of infusions with AEs
number (%) of infusion rate reduction/interruption/discontinuation due to AE,
Incidence of anti-rHuPH20 antibodies
Rates of systemic and local AEs
Epoch 2: IV Treatment Period
Safety
Number (%) of subjects with AE's
Number (%) of infusions with AEs
number (%) of infusion rate reduction/interruption/discontinuation due to AE
Rates of systemic and local AEs
Efficacy
1. Proportion of subjects with clinically meaningful improvement in functional ability defined as a decrease of ≥1 point in the adjusted INCAT disability score OR who experience CIDP improvement (defined as ≥8 kPa increase in the hand grip strength in the more affected hand OR ≥4 points increase in R-ODS) at the completion of the IV treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Epoch 1: Double blind. Epoch 2: open label |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 57 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Austria |
Brazil |
Canada |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Israel |
Italy |
Mexico |
Norway |
Poland |
Portugal |
Russian Federation |
Serbia |
Slovakia |
Spain |
Sweden |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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study completion is last subject last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |