Primary Sjögren's Syndrome Painful Sensory Neuropathies, Sjogrens Disease
Conditions
Brief summary
This study aims to assess the efficacy and safety of efgartigimod PH20 in adults with Sjogren's Disease (SjD) associated with nerve damage. The study will assess how efgartigimod PH20 affects symptoms of SjD specifically linked to the peripheral nervous system; the safety and tolerability of efgartigimod PH20; and whether receiving efgartigimod PH20 affects the participant's quality of life.
Detailed description
The study will be conducted in adult participants with moderate-to-severe SjD and SjD-associated sensorimotor polyneuropathy (SMPN) or sensory polyneuropathy (SPN). The study consists of two parts. Part A is a randomized, double-blinded, placebo-controlled, parallel-group treatment period designed to evaluate the efficacy and safety of efgartigimod hyaluronidase (PH20) subcutaneously (SC) or placebo. Following the completion of part A, the double-blinded treatment period (DBTP) participants will enter part B, an open-label treatment period (OLTP) to assess long-term safety, tolerability, and durability of response of efgartigimod PH20 SC. The overall study duration will be up to 108 weeks for each participant.
Interventions
BIOLOGICALefgartigimod PH20 SC
subcutaneous efgartigimod PH20 SC given by prefilled syringe
OTHERPlacebo PH20 SC
subcutaneous placebo PH20 SC given by prefilled syringe
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is at least 18 years of age and the local legal age of consent for clinical studies when signing the ICF * Meets the following SjD criteria: Fulfilled American College of Rheumatology and the European Alliance of Associations for Rheumatology classification 2016 SjD criteria before screening; Moderate-to-severe disease defined as a ESSDAI ≥ 5 or clinESSDAI ≥ 6 with PNS domain score of ≥ 5 (ie, a score of at least low activity) at screening; Anti-Ro/SS-A positive at a central laboratory at screening * Meets the following SjD-associated polyneuropathy criteria: Diagnosis of SjD-associated SMPN, SPN or sensory ganglionopathy, with neuropathy duration ≤ 5 years at screening and signs of active neuropathic disease development within the last 12 months; patients with co-existing SjD-associated small fiber neuropathy are eligible; No alternative diagnosis of neuropathy etiology; Total mTCNS ≥ 6 at screening; mTCNS sensory test score \<level 3 at screening (does not apply to sensory ganglionopathy cohort where any severity is acceptable)
Exclusion criteria
* Besides the indication under study, known medical conditions that would interfere with an accurate assessment of clinical symptoms of SjD-associated SMPN or SPN or gangliopathy, confound the study results, or puts the participant at undue risk. * Associated (also known as secondary) SjD, defined as overlap with another autoimmune rheumatic or systemic inflammatory condition (eg, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or idiopathic inflammatory myopathy). * Active fibromyalgia which is not adequately controlled in the judgment of the investigator, or participant is receiving fibromyalgia treatment that has not been stable treatment for at least 12 weeks before screening. * An alternative etiology for SMPN/SPN/sensory ganglionopathy or insufficient evidence of the diagnosis. * Any severe SjD manifestation or other health condition not adequately controlled at screening or baseline that may put the participant at undue risk based on the investigator's opinion. * Comorbidities (eg, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic (oral, IV, or IM) glucocorticoids within the previous 12 months. * History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥ 3 years; before first IMP administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in modified Toronto Clinical Neuropathy Score (mTCNS) total score at the end of Part A | Up to 48 weeks | The mTCNS (modified Toronto Clinical Neuropathy Score) is a clinician-reported outcome measure derived from the original TCNS to improve sensitivity to early and mild neuropathy and to enhance feasibility and consistency inclinical research settings. The total mTCNS score is calculated as the sum of the symptom and sensory subscores, yielding a total possible score range of 0 to 33, with higher scores indicating greater neuropathy severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in modified Toronto Clinical Neuropathy Score (mTCNS) total score over time | up to 96 weeks | The mTCNS (modified Toronto Clinical Neuropathy Score) is a clinician-reported outcome measure derived from the original TCNS to improve sensitivity to early and mild neuropathy and to enhance feasibility and consistency inclinical research settings. The total mTCNS score is calculated as the sum of the symptom and sensory subscores, yielding a total possible score range of 0 to 33, with higher scores indicating greater neuropathy severity. |
| Change from baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score at the end of part A and over time | up to 96 weeks | The Norfolk QoL-DN is a patient-reported outcome (PRO) instrument designed to assess neuropathy symptom severity and the impact of peripheral neuropathy on participants' ability to complete activities of daily living (ADLs). The Norfolk QoL-DN consists of 35 items that assess the presence and severity of sensory symptoms (eg, numbness, tingling, pain), motor and balance difficulties, and the extent to which neuropathy interferes with daily activities, sleep, work, and social functioning. |
| Change from baseline in clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI) score at the end of part A and over time | up to 96 weeks | The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) was designed to measure systemic disease activity in patients with SjD. The ESSDAI consists of 12 domains, and the final score falls between 0 (no disease activity) and, theoretically, 123 (maximum disease activity). Clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI) includes all ESSDAI domains except the biological domain. The clinical domains in clinESSDAI have different weights than in ESSDAI. |
| Change from baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score at the end of part A and over time | up to 96 weeks | The ESSDAI was designed to measure systemic disease activity in patients with SjD. The ESSDAI consists of 12 domains, and the final score falls between 0 (no disease activity) and, theoretically, 123 (maximum disease activity). |
| Proportion of participants with low disease activity (clinESSDAI < 5) at the end of part A and over time | up to 96 weeks | The ESSDAI was designed to measure systemic disease activity in patients with SjD. The ESSDAI consists of 12 domains, and the final score falls between 0 (no disease activity) and, theoretically, 123 (maximum disease activity). clinESSDAI includes all ESSDAI domains except the biological domain. The clinical domains in clinESSDAI have different weights than in ESSDAI. |
| Incidence of AEs | Up to 104 weeks | Incidents are identified by measuring clinically significant changes in vital signs, physical examination, ECG, and clinical laboratory safety evaluations. |
| Change from baseline in Neuropathic Pain Questionnaire (NPQ) at the end of part A and over time | up to 96 weeks | The NPQ is a self-administered PRO used to characterize the qualitative features of neuropathic pain. Responses are combined using a predefined scoring algorithm to generate a summary score reflecting the presence and prominence of neuropathic pain features. |
| Change from baseline in the Difficulty Thinking Numerical Rating Scale (NRS) at the end of part A and over time | up to 96 weeks | The Difficulty Thinking Numerical Rating Scale (NRS) is a SjD-specific symptom severity diary that has been developed specifically for the purpose of assessing disease severity in participants with SjD. An 11-point Likert response scale is used from 0 (no difficulty thinking) to 10 (worst possible difficulty thinking). |
| Change from baseline in Patient Global Impression of Severity (PGIS) scores at the end of part A and over time | up to 96 weeks | The PGIS of neuropathy severity is a single-item questionnaire that asks participants to provide a self-assessment of their overall neuropathy severity, using a 5-point scale. |
| Change from baseline in Patient Global Impression of Change (PGIC) scores at the end of part A and over time | up to 96 weeks | The PGIC of neuropathy severity is a single-item questionnaire that asks the participant to provide a self-assessment of change in their neuropathy severity using a 7-point scale compared to just before the participant started taking the IMP. |
| Change from baseline in Clinical Global Impression of Severity (CGIS) scores at the end of part A and over time | up to 96 weeks | The CGI of SjD-associated SMPN or SPN severity is a 1-item questionnaire that asks the clinician to provide an assessment of their patients' neuropathy severity on a 5-point scale at the time of the visit. |
| Change from baseline in Clinical Global Impression of Change (CGIC) scores at the end of part A and over time | up to 96 weeks | The CGIC of SjD-associated SMPN or SPN severity is a 1-item questionnaire that asks the clinician to provide the overall change in their patients' neuropathy severity on a 7-point scale, compared to just before participant started taking the IMP. |
| Change from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scores at the end of part A and over time | up to 96 weeks | The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale assesses fatigue and its impact on patient's everyday lives, with a 7-day recall. It comprises 13 items, with responses of each of the items using a 5-point Likert scale ranging from 1 (Not at all) to 5 (Very much). |
Outcome results
None listed