E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic lupus erythematosus (SLE) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10038359 - Renal and urinary disorders |
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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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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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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Males and females, age 18 through 70 years, inclusive, at Screening •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 SLE as defined at Screening as confirmed by Sponsor or designee, and at Baseline (i.e., prior to randomization on Day 1) as confirmed by Investigator • Stable, appropriate standard of care for SLE
List of extended Inclusion Criteria changes only below. Please see protocol for full list:
1. Males and females, age 18 through 70 years, inclusive, at Screening.
3. Subjects must have a positive anti-nuclear antibodies (ANA) (titer ≥ 1:80) and/or elevated anti-dsDNA and/or elevated anti-Smith antibody test (if the screening test(s) are negative [based on central or local testing], then an historic positive serology for ANA, elevated anti-dsDNA, and/or elevated anti-Smith antibody test, with unequivocal documentation, may be accepted).
7. Subjects must be on appropriate SOC (i.e., at least one anti-malarial or an immunosuppressant) for SLE, based on the Investigator's judgement. If taking the following medications, the subject must be on a stable dose prior to Baseline (i.e., Day 1 prior to randomization) for the period of time specified below, and must intend to continue at stable doses throughout the 24-week Treatment Period, unless otherwise specified by this protocol:
8. Willing to provide consent for serial photographic documentation of any cutaneous manifestations of SLE, and/or oral mucocutaneous lesions (including aphthous ulcers) not attributed to SLE, from Screening through the EoS.
11. Should be up-to-date on all age-appropriate vaccinations, including COVID-19, per local and professional guidelines for immunocompromised individuals (e.g., CDC, local professional society guidelines).
12. Peripheral venous access anticipated to be adequate to tolerate planned dosing regimen of IV infusions and blood draws Q2W per Table 1
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E.4 | Principal exclusion criteria |
• Life-threatening or organ system-threatening SLE activity, that is sufficiently active that it is expected to require increase in treatment during the study • Proteinuria consistent with nephrotic syndrome: ≥ 3.5 g proteinuria/day, estimated based on urine protein-creatinine ratio (UPCR) ≥ 350 mg/mmol at Screening • Active lupus-related neuropsychiatric disease (with the exceptions of mild stable lupus headache, fatigue, mild stable organic brain syndrome) • Drug-induced lupus • Evidence of active infection or risk or history of serious infection with tuberculosis; hepatitis B, hepatitis C; HIV • Evidence of active infection with SARS-CoV-2
List of extended Inclusion Criteria changes only below. Please see protocol for full list:
5. h. Current or recent (within the past 12 months) history of alcoholism or significant drug abuse (recreational use of cannabis is not an exclusion criterion).
6. a. Active or latent TB (refer to §6.7 for specific requirements for TB screening). Subjects with a history of latent TB are allowed with documentation of completed treatment with a regimen recommended by an appropriate local or national health authority (e.g., CDC). b. Hepatitis B virus: serologic evidence of hepatitis B infection based on the results of testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) as follows: i. Subjects positive for HBsAg are excluded. ii. Subjects negative for HBsAg but positive for HBcAb, regardless of HBsAb status will be excluded. c. Hepatitis C virus (HCV): HCV RNA detectable in any subject with positive HCV antibody. d. Seropositivity for HIV at Screening. e. Positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 at Screening. f. History of progressive multifocal leukoencephalopathy. g. Receipt of oral or parenteral anti-infectives (antibacterials, antivirals, antifungals, or antiparasitic agents) for infection, ≤ 2 weeks prior to Day 1 (NOTE: chronic oral antibiotics used for prophylaxis may be permitted, dependent on discussion with, and agreement of, the Medical Monitor).
14. Functional class IV as defined by the ACR 1991 Revised Criteria for the Classification of Global Functional Status in Rheumatoid Arthritis.
15. e. Biologic therapies, including but not limited to: atacicept, telitacicept, belimumab, abatacept, belatacept, anifrolumab, inhibitors of interleukin (IL) pathways IL-6, IL-12/23, IL-17, IL-1, tumor necrosis factor α, or interferon α: 12 weeks (exception: the use of prophylactic COVID-19 monoclonal antibodies in immunocompromised subjects is encouraged as per Principal Investigator's discretion and local guidelines). j. Combination therapy with ≥ 2 immunosuppressants for the treatment of SLE: A discussion with, and agreement by, the Medical Monitor and Sponsor will be required.
18. Known hypersensitivity to ALPN-101, components thereof, or excipients contained in the drug formulation.
19. Any condition or circumstances which in the opinion of the Investigator or Sponsor may make a subject unlikely or unable to complete the study or comply with study procedures and requirements.
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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: • British Isles Lupus Assessment Group index (BILAG) 2004 • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI- 2K); SLEDAI-2K 30-Day (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 Joint Count-28 (SJC-28) • Tender Joint Count-28 (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 Assessment tools: • Patient's Global Assessment of Disease Activity (PtGA) • Short Form-36 (SF-36) health survey • 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 concentration (Cmax), area under the concentration-time curve (AUC), and trough concentration (Ctrough) at the end of dosing intervals.
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 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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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 | 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 |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
Taiwan |
Korea, Republic of |
Russian Federation |
United States |
France |
Germany |
Hungary |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |