A Study to Assess the Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP, an Autoimmune Disorder That Affects the Peripheral Nerves)

Study Overview
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Brief Summary
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This is a Phase 2 study to evaluate the safety and efficacy of the subcutaneous formulation of efgartigimod in adults with CIDP.

Official Title
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A Phase 2 Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Conditions
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Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Intervention / Treatment
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* Biological: efgartigimod PH20 SC in stage B
* Other: placebo in stage B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the requirements of the trial, provide written informed consent (include consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits) Male or female patient aged 18 years or older, at the time of signing the informed consent. Diagnosed with probable or definite CIDP according to criteria of the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS 2010), progressing or relapsing forms. CIDP Disease Activity Status (CDAS) score ≥2 at screening. INCAT score ≥2 at the first run-in visit (for patients entering run-in) or stage A baseline (for treatment-naïve patients with documented evidence for worsening on the total adjusted INCAT disability score within 3 months prior to screening). Patients with an INCAT score of 2 at trial entry must have this score exclusively from the leg disability score; for patients with an INCAT score of ≥3 at trial entry, there are no specific requirements for arm or leg scores. Fulfilling any of the following treatment conditions: Currently treated with pulsed corticosteroids, oral corticosteroids equivalent to prednisolone/prednisone ≤10mg/day, and/or IVIg or SCIg, if this treatment has been started within the last 5 years before screening, and the patient is willing to discontinue this treatment at the first run-in visit; or Without previous treatment (treatment-naive); or Treatment with corticosteroids and/or IVIg or SCIg discontinued at least 6 months prior to screening Note: Patients not treated with monthly or daily corticosteroids, IVIg or SCIg for at least 6 months prior to screening are considered as equal to treatment-naïve patients. Women of childbearing potential who have a negative pregnancy test at screening and a negative urine pregnancy test up to Stage A baseline. Women of childbearing potential must use an acceptable method of contraception from signing the ICF until the date of the last dose of IMP Exclusion Criteria: Pure sensory atypical CIDP (EFNS/PNS definition). Polyneuropathy of other causes, including the following: Multifocal motor neuropathy; Monoclonal gammopathy of uncertain significance with anti-myelin associated, glycoprotein immunoglobulin M (IgM) antibodies; Hereditary demyelinating neuropathy; Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes; Lumbosacral radiculoplexus neuropathy; Polyneuropathy most likely due to diabetes mellitus; Polyneuropathy most likely due to systemic illnesses; Drug- or toxin-induced polyneuropathy. Any other disease that could better explain the patient's signs and symptoms. Any history of myelopathy or evidence of central demyelination. Current or past history (within 12 months of screening) of alcohol, drug or medication abuse. Severe psychiatric disorder (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol. Patients with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV): serologic panel test results indicative of an active (acute or chronic) infection; Active Hepatitis C Virus (HCV): serology positive for HCV-Ab; Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count ≤200 cells/mm3. Total IgG level <6 g/L at screening. Treatment with the following: Within 3 months (or 5 half-lives of the drug, whichever is longer) before screening: plasma exchange or immunoadsorption, any concomitant Fc-containing therapeutic agents or other biological, or any other investigational product; Within 6 months before screening: rituximab, alemtuzumab, any other monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, any other immunomodulating or immunosuppressive medications, and oral daily corticosteroids >10 mg/day. Note: Patients using IVIg, SCIg, pulsed corticosteroids, and oral daily corticosteroids ≤10 mg/day can be included. Patients who (intend to) use prohibited medications and therapies (see protocol) during the trial. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after last IMP administration. Patients with any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of CIDP. Patients who received a live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated, sub-unit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first IMP administration. Patients with the following cancer can be included anytime: Adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, or Incidental histological finding of Prostate cancer (TNM [tumor, nodes, and metastases classification] stage T1a or T1b). Patients who previously participated in a trial with efgartigimod and have received at least one administration of IMP. Patients with known medical history of hypersensitivity to any of the ingredients of IMP. Patients with clinical evidence of other significant serious disease or patients who underwent a recent or have a planned major surgery, or any other reason which could confound the results of the trial or put the patient at undue risk.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efgartigimod PH20 SC<br>patients receiving efgartigimod PH20 SC in both stage A as stage B | Biological: efgartigimod PH20 SC in stage B<br>* Stage A: efgartigimod PH20 SC, Stage B: efgartigimod PH20 SC<br>|
| Placebo Comparator: Placebo<br>patients receiving efgartigimod PH20 SC during stage A and receiving placebo in stage B | Biological: efgartigimod PH20 SC in stage B<br>* Stage A: efgartigimod PH20 SC, Stage B: efgartigimod PH20 SC<br>Other: placebo in stage B<br>* Stage A: N/A, stage B: placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage A: Percentage of patients with confirmed evidence of clinical improvement(ECI) |  | Up to 12 weeks during the open-label stage A | 
| Stage B: Time to first adjusted INCAT deterioration compared to Stage B baseline |  | Up to 48 weeks during the randomized placebo-controlled stage B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage A: Time to initial confirmed ECI |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Change from Stage A baseline over time in adjusted INCAT score |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Change from Stage A baseline over time in Medical Research Council (MRC) Sum score |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Change from Stage A baseline over time in I-RODS disability scores |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Change from Stage A baseline over time in TUG score |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Change from Stage A baseline over time in mean grip strength |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Exposure adjusted occurrence of treatment-emergent (serious) adverse events |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Incidence of clinically significant laboratory abnormalities |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Pre-dosing efgartigimod serum concentrations over time |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Changes of serum IgG levels over time |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20 |  | Up to 12 weeks during the open-label stage A | 
| Stage A: Changes from D1A in EQ-5D-5L over time |  | Up to 12 weeks during the open-label stage A | 
| Stage B: Time to CIDP disease progression | Time to CIDP disease progression is defined by the time from first dose of double-blind IMP to the first I-RODS score decrease ≥4 points compared to Stage B baseline using the centile metric. | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Percentage of patients with improved functional level compared to Stage B baseline |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Change from Stage B baseline over time in adjusted INCAT score |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Change from Stage B baseline over time in MRC Sum score |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Change from Stage B baseline over time in 24-item I-RODS disability score |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Change from Stage B baseline over time in TUG score |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Change from Stage B baseline over time in mean grip strength |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Time to 10% decrease in the 24-item I-RODS |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Exposure adjusted occurrence of treatment-emergent adverse events and serious adverse events |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Incidence of clinically significant laboratory abnormalities |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Pre-dosing efgartigimod serum concentrations over time |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Changes of serum IgG levels over time |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20 |  | Up to 48 weeks during the randomized placebo-controlled stage B | 
| Stage B: Changes from D1A in EQ-5D-5L over time |  | Up to 48 weeks during the randomized placebo-controlled stage B |