E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic lupus erythematosus (SLE) |
Lupus érythémateux disséminé (LED)
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E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus |
Lupus systémique |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042946 |
E.1.2 | Term | Systemic lupus erythematosus rash |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042948 |
E.1.2 | Term | Systemic lupus erythematosus syndrome aggravated |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042947 |
E.1.2 | Term | Systemic lupus erythematosus synd |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029142 |
E.1.2 | Term | Nephritis systemic lupus erythematosus |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067657 |
E.1.2 | Term | Systemic lupus erythematosus disease activity index increased |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 | 10067658 |
E.1.2 | Term | Systemic lupus erythematosus disease activity index decreased |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067659 |
E.1.2 | Term | Systemic lupus erythematosus disease activity index abnormal |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080670 |
E.1.2 | Term | Systemic lupus erythematosus reactivation |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 | 10073694 |
E.1.2 | Term | Lupus pleurisy |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040968 |
E.1.2 | Term | SLE arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of ALPN-101 compared to placebo in subjects with moderate to severe active SLE
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Évaluer la tolérance et la sécurité d’emploi de l’ALPN-101 par rapport au placebo chez des patients présentant un LED modéré à sévère
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of ALPN-101 in subjects with active SLE • To assess the pharmacokinetics (PK) of ALPN-101 in active SLE • To assess the incidence of anti-drug antibodies (ADA) against ALPN-101
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• Évaluer l’efficacité de l’ALPN-101 chez des patients présentant un LED actif • Évaluer la pharmacocinétique (PK) de l’ALPN-101 dans le LED actif • Évaluer l’incidence des anticorps anti-médicament (AAM) dirigés contre l’ALPN-101
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Written informed consent •Age 18 to 65 •Diagnosis of lupus for ≥ 6 months prior to Screening •Positive ANA and/or elevated anti-dsDNA and/or elevated anti-Smith antibody test at Screening •Active lupus at Screening and Baseline, as defined per-protocol and confirmed by the study's medical monitor •Standard lupus medications must be stable prior to Screening •Women must have a PAP smear and known HPV status within 12 months of Day 1 •All participants must use highly effective birth control if they/their partner are capable of becoming pregnant
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• Consentement éclairé écrit • Age de 18 à 65 ans • Diagnostic de lupus pendant ≥ 6 mois avant la sélection • Test ANA positif et / ou anti-dsDNA et / ou anticorps anti-Smith élevé lors de la sélection • Lupus actif à la sélection et à l’inclusion, tel que défini par protocole et confirmé par le moniteur médical de l'étude • Les médicaments standard contre le lupus doivent être stables avant la sélection • Les femmes doivent avoir un frottis PAP et un statut HPV connu dans les 12 mois avant le jour 1 • Toutes les participantes doivent utiliser une méthode de contraception hautement efficace si elles / leur partenaire sont capables de devenir enceintes |
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E.4 | Principal exclusion criteria |
•Life-threatening or organ system-threatening lupus activity that is anticipated to require increased treatment during the study •Proteinuria consistent with nephrotic syndrome •Active lupus-related neuropsychiatric disease •Drug-induced lupus •Any serious health condition that would place the subject at undue risk from the study or would confound interpretation of safety or efficacy outcomes •Recent or serious ongoing infection; risk or history of serious infection •Receipt of live vaccination within 8 weeks of Day 1, or expected to require live vaccination during the study •Unacceptable Screening laboratory results •History of new, ongoing, or recurrent malignancy ≤ 5 years prior to Day 1, with some exceptions per-protocol •Pregnant or breastfeeding at the time of screening, or plans to become pregnant ≤ 3 months following the last dose of study drug •Prior diagnosis of, or fulfills diagnostic criteria for, another rheumatic disease that overlaps with lupus or another autoimmune or inflammatory disease that may confound clinical assessments or increase subject risk in the study •Diagnosis of, or fulfills diagnostic criteria for, fibromyalgia •Functional class IV lupus •Does not meet protocol washout periods for concomitant medications •Serious lupus disease activity, which warrants immediate immunosuppressive therapy not appropriate for the study or which makes the possibility of receiving placebo or investigational agent an inappropriate risk •Ongoing participation in another therapeutic clinical trial •Known hypersensitivity to ALPN-101, components thereof, or excipients contained in the drug formulation
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• Activité lupique mettant en jeu le pronostic vital ou menaçant le système organique et qui devrait nécessiter un traitement accru au cours de l’étude • Protéinurie compatible avec le syndrome néphrotique • Maladie neuropsychiatrique active liée au lupus • Lupus d'origine médicamenteuse • Tout problème de santé grave qui exposerait le sujet à un risque indu de l'étude ou qui confondrait l'interprétation des résultats d'innocuité ou d'efficacité • Infection récente ou grave en cours; risque ou antécédents d'infection grave • Réception d'un vaccin vivante dans les 8 semaines suivant le jour 1, ou devant nécessiter un vaccin vivante pendant l'étude • Résultats de laboratoire inacceptables à la sélection • Antécédents de malignité nouvelle, en cours ou récurrente ≤ 5 ans avant le jour 1, à quelques exceptions près par protocole • Enceinte ou qui allaite au moment de la sélection , ou prévoit de devenir enceinte ≤ 3 mois après la dernière dose du médicament à l'étude • Diagnostic préalable d'une autre maladie rhumatismale ou remplissant les critères de diagnostic d'une autre maladie rhumatismale qui chevauche le lupus ou une autre maladie auto-immune ou inflammatoire pouvant perturber les évaluations cliniques ou augmenter le risque du sujet dans l'étude • Diagnostic de la fibromyalgie ou remplit les critères diagnostiques de la fibromyalgie • Lupus fonctionnel de classe IV • Ne pas respecter les périodes de sevrage du protocole pour les médicaments concomitants • Activité lupique grave, qui justifie un traitement immunosuppresseur immédiat non approprié pour l'étude ou qui rend la possibilité de recevoir un placebo ou un agent expérimental un risque inapproprié • Participation continue à un autre essai clinique thérapeutique • Hypersensibilité connue à l’ALPN-101, à des composants ou aux excipients contenus dans la formulation du médicament |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability will be assessed by evaluating the type, frequency, severity, and seriousness of adverse events, including clinically significant changes in symptoms, physical exam findings, vital signs, laboratory tests (hematology, serum chemistries and coagulation, urinalysis), and electrocardiograms. |
La tolérance et la sécurité d’emploi seront évaluées en déterminant le type, la fréquence, la sévérité et la gravité des événements indésirables, y compris les modifications cliniquement significatives des symptômes, des résultats de l’examen clinique, des signes vitaux, des analyses biologiques (hématologie, biochimie sanguine et bilan de coagulation, analyse d’urine) et électrocardiogrammes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
According to protocol |
Selon le protocole |
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E.5.2 | Secondary end point(s) |
Efficacy Endpoints: Efficacy endpoints will be assessed by evaluating disease activity relative to baseline and across treatment groups using the tools and assessments listed below, and derivatives calculated from them (e.g. SLE Responder Index [SRI] -4, -5, -6 response; time to and proportion with flare of SLE; others). -Global disease Activity Assessment Tools: • BILAG 2004 • SLEDAI-2K; SLEDAI-2K 30 • Physician’s Global Assessment of SLE Disease Activity (PhGA) -Organ-Specific Disease Activity Assessment Tools: • Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), with photography when appropriate • Swollen joints based on assessment of 28 joints (SJC-28) • Tender joints based on assessment of 28 joints (TJC-28) • Estimated glomerular filtration rate (eGFR) • Proteinuria assessed as urine protein to creatinine ratio (UPCR), • Urinary sediment analysis for hematuria, pyuria, and red cell casts -Patient Reported Outcomes and Quality of Life (QoL) Assessment tools: • Patient’s Global Assessment of Disease Activity (PtGA) • Short Form Health Survey-36 (SF-36) • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) (13-Item) -Clinical Biomarkers of SLE Activity: • High-sensitivity C-reactive protein (hsCRP) • Complement levels: C3, C4, CH50 • Anti-dsDNA antibodies -Corticosteroids: • Dose of oral and parenteral corticosteroids
Pharmacokinetic Endpoints: Serum concentrations of ALPN-101 will be measured. Pharmacokinetic endpoints include estimates of maximum observed concentration (Cmax), area under the concentration-time curve (AUC), and trough concentration at the end of dosing intervals (Ctrough).
Immunogenicity Endpoints: The presence and titer of ADA against ALPN-101 will be assessed at Baseline (prior to study drug administration on Day 1) and at intervals throughout the study. Samples confirmed positive for ADA may be explored for neutralizing (NAb) capacity. The relationship between ADA and PK will be analyzed; relationship between ADA and clinical outcomes may be explored.
Pharmacodynamic Endpoints: Blood and urine will be collected at intervals; target saturation by ALPN-101 on circulating lymphocytes will be assessed; plasma, sera and peripheral blood mononuclear cells (PBMCs) will be prepared and may be assessed for biomarkers.
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Les critères d’efficacité: Les critères d’efficacité seront examinés en évaluant l’activité de la maladie par rapport à l’inclusion et dans les groupes de traitement, à l’aide des outils et évaluations répertoriés ci-dessous et de leurs dérivés (par exemple, réponse SRI-4, -5, -6 [SRI : SLE Responder Index, indice de répondeurs SLE]; délai avant la survenue d’une poussée et proportion de patients présentant une poussée de LED; autres). Outils d’évaluation globale de l’activité de la maladie : • BILAG 2004 • SLEDAI-2K ; SLEDAI-2K 30 • Évaluation globale de l’activité du LED, effectuée par le médecin (PhGA, Physician’s Global Assessment of SLE Disease Activity) Outils d’évaluation de l’activité de la maladie spécifiques aux organes : • Indice de sévérité et de surface de l’atteinte LED cutanée (CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index), avec photographie le cas échéant • Nombre d’articulations gonflées sur la base de l’examen de 28 articulations (SJC-28, Swollen joints based on assessment of 28 joints) Nombre d’articulations douloureuses sur la base de l’examen de 28 articulations (TJC-28, tender joints based on assessment of 28 joints) • Débit de filtration glomérulaire estimé (DFGe) • Protéinurie évaluée par le rapport protéines/créatinine urinaires (UPCR, urine protein to creatinine ratio), • Analyse du sédiment urinaire à la recherche d’une hématurie, d’une pyurie et de cylindres hématiques Outils d’évaluation des résultats rapportés par le patient (PRO, Patient reported outcomes) et de la qualité de vie (QdV) • Évaluation globale de l’activité de la maladie, effectuée par le patient (PtGA, Patient’s Global Assessment of Disease Activity) • Questionnaire de santé succinct à 36 rubriques (SF-36, 36-Item Short Form Health Survey) • Évaluation fonctionnelle du traitement des maladies chroniques-Fatigue (FACIT−F, Functional Assessment of Chronic Illness Therapy-Fatigue) (13 rubriques) Biomarqueurs de l’activité du LED : • Protéine C réactive de haute sensibilité (hsCRP) • Taux de complément : C3, C4, CH50 • Anticorps anti-ADNdb Corticoïdes : • Dose de corticoïdes oraux et parentéraux
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to protocol |
Selon le protocole |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogénicité |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Korea, Republic of |
Russian Federation |
United States |
France |
Germany |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |