Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruiting
Participants planned
126
Countries
5
Sites
13
Autoimmune Cytopenias (warm autoimmune hemolytic anemia [wAIHA], cold agglutinin disease [CAD], immune thrombocytopenia [ITP])
To evaluate the safety and tolerability of povetacicept in subjects with autoimmune cytopenias.
Key facts
- Sponsor
- Alpine Immune Sciences Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20], Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Trial duration
- 15 May 2024 → ongoing
- Decision date (initial)
- 2024-04-22
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Alpine Immune Sciences, Inc.
External identifiers
- EU CT number
- 2023-507067-19-00
- ClinicalTrials.gov
- NCT05757570
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Pharmacodynamic, Pharmacokinetic, Safety
To evaluate the safety and tolerability of povetacicept in subjects with autoimmune cytopenias.
Secondary objectives 3
- To assess the efficacy of povetacicept in subjects with autoimmune cytopenias.
- To assess the PK of povetacicept in subjects with autoimmune cytopenias.
- To assess the incidence of anti-drug antibodies (ADA) against povetacicept in subjects with autoimmune cytopenias.
Conditions and MedDRA coding
Autoimmune Cytopenias (warm autoimmune hemolytic anemia [wAIHA], cold agglutinin disease [CAD], immune thrombocytopenia [ITP])
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.0 | LLT | 10083843 | Primary immune thrombocytopenia | 10005329 |
| 20.0 | LLT | 10068863 | Cold agglutinin disease | 10005329 |
| 25.0 | LLT | 10087092 | Warm autoimmune hemolytic anemia | 100000004848 |
Study design 6 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Part 1 - Treatment Period Subjects who meet the eligibility criteria for the study will start treatment with povetacicept and receive treatment for up to 6 cycles (6 doses). When the first 7 subjects in each cohort have been enrolled and treated with 3 cycles of povetacicept (12 weeks), an interim analysis will be conducted to assess safety and efficacy and to determine if the indication cohort should stop enrolment for futility or lack of efficacy.
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
|
| 2 | Part 1 - Optional Treatment Extension Period At the end of the Part 1 Treatment Period, subjects who are experiencing a treatment benefit, based on the investigator's judgment, may choose to continue into the Part 1 Optional Treatment Extension Period to receive up to 6 more cycles of treatment with povetacicept.
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
|
| 3 | Part 1 - Follow-up Subjects will have an end of treatment visit either at the end of the Part 1 Treatment Period or at the end of the Part 1 Optional Treatment Extension Period. After the end of treatment, subjects will be monitored for safety follow-up for an additional 8 weeks.
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
|
| 4 | Part 2 - Expansion Treatment Period Part 2 will enroll new subjects in a given cohort to gain additional experience with the 240 mg Q4W dose level (as well as a potential lower dose level, based on emerging data). Part 2 may include 1 or 2 dose levels at or below the dose level determined to be safe and effective in Part 1. If 2 dose levels are tested, subjects will be randomized within the indication cohort. Each dose level within the indication cohort may enroll up to 14 subjects. Subjects who meet the eligibility criteria for the study will start treatment with povetacicept and receive treatment for up to 6 cycles (6 doses).
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
|
| 5 | Part 2 - Optional Treatment Extension Period At the end of the Part 2 Expansion Treatment Period, subjects who are experiencing a treatment benefit, based on the investigator's judgment, may choose to continue into the Part 2 Optional Treatment Extension Period to receive up to 6 more cycles of treatment with povetacicept.
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
|
| 6 | Part 2 – Follow-up Subjects will have an end of treatment visit either at the end of the Part 2 Treatment Period or at the end of the Part 2 Optional Treatment Extension Period. After the end of treatment, subjects will be monitored for safety follow-up for an additional 8 weeks.
|
Not Applicable | None | wAIHA (warm autoimmune hemolytic anemia): At least 7 and up to 14 subjects with wAIHA in Part 1 of the study; up to 28 subjects in Part 2 of the study CAD (cold agglutinin disease): At least 7 and up to 14 subjects with CAD in Part 1 of the study; up to 28 subjects in Part 2 of the study ITP (immune thrombocytopenia): At least 7 and up to 14 subjects with ITP in Part 1 of the study; up to 28 subjects in Part 2 of the study |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Indication-specific Criteria a. Immune Thrombocytopenia (ITP) * Documented persistent or chronic primary ITP of at least 12 weeks duration * History of failure or relapse to at least 2 treatment regimens for ITP * A documented history of response to IVIg or steroids * History of exposure to a TPO-RA unless otherwise contraindicated or unavailable * Documented history of platelets <30 × 10^9/L b. Warm Autoimmune Hemolytic Anemia (wAIHA) * Diagnosis of primary wAIHA of at least 12 weeks duration documented with a current or prior positive direct antiglobulin test (DAT) for anti-IgG (±C3d) * Documented history of anemia with hemoglobin ≤10 g/dL * At least one of the following: (i) haptoglobin LLN (iii) lactate dehydrogenase >ULN * History of failure or relapse to at least 2 treatment regimens for wAIHA c. Cold Agglutinin Disease (CAD) * Diagnosis of primary CAD of at least 12 weeks duration with all of the following: (i) chronic hemolysis (ii) polyspecific DAT positive (iii) monospecific DAT strongly positive for C3d (iv) cold agglutinin titer ≥64 at 4°C (v) IgG DAT ≤1+ (vi) no overt malignant disease * Documented history of anemia with hemoglobin ≤10 g/dL * Evidence of hemolysis: (i) indirect bilirubin>ULN and (ii) lactate dehydrogenase >ULN or haptoglobin
- (All indications) If receiving protocol-specified standard-of-care medications, doses must be stable for protocol-specified durations
- Indication-specific Criteria for Warm Autoimmune Hemolytic Anemia (wAIHA) and Cold Agglutinin Disease (CAD): Documentation of folic acid and vitamin B12 within normal ranges
Exclusion criteria 3
- Secondary AIHA, CAD, or ITP
- Treatment with any of the following within the noted period prior to study entry a. rituximab: <12 weeks b. IVIg: <4 weeks c. sutimlimab: any use after initiation of screening is exclusionary, other marketed biologic therapeutics: <8 weeks d. plasmapheresis, plasma exchange, or double-filtration plasmapheresis: <8 weeks e. transfusions with blood, blood products or other rescue medications: 2 weeks f. splenectomy: <12 weeks g. other immunomodulatory or investigational agents, except for investigational agents for COVID-19 that have been granted emergency use authorization or approved by the applicable national health authority: <5 half-lives and requires agreement of the Medical Monitor
- Recent serious or ongoing infection; risk or history of serious infection.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Type, incidence, severity, and seriousness of AEs.
Secondary endpoints 1
- Assessment of efficacy, PK, and ADA
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10723902 · Product
- Active substance
- Povetacicept
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 240 mg milligram(s)
- Max total dose
- 240 mg milligram(s)
- Max treatment duration
- 48 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- ALPINE IMMUNE SCIENCES INC
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Alpine Immune Sciences Inc.
- Sponsor organisation
- Alpine Immune Sciences Inc.
- Address
- 188 East Blaine Street
- City
- Seattle
- Postcode
- 98102-3983
- Country
- United States
Scientific contact point
- Organisation
- Alpine Immune Sciences Inc.
- Contact name
- Melissa Gardner
Public contact point
- Organisation
- Alpine Immune Sciences Inc.
- Contact name
- Jeanne Paine
Third parties 11
| Organisation | City, country | Duties |
|---|---|---|
| 4g Clinical LLC ORG-100042775
|
Wellesley, United States | Interactive response technologies (IRT) |
| Confidence Pharmaceutical Research LLC ORG-100049606
|
Redwood City, United States | On site monitoring, Code 12, Code 13, Code 5, Code 8 |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other, Data management |
| PPD International Holdings LLC ORG-100007655
|
Zaventem, Belgium | Laboratory analysis |
| Sanquin Diagnostiek B.V. ORG-100032297
|
Amsterdam, Netherlands | Laboratory analysis |
| Pharmaceutical Product Development LLC ORG-100016999
|
Richmond, United States | Laboratory analysis |
| Pharmaceutical Product Development LLC ORG-100016999
|
Highland Heights, United States | Laboratory analysis |
| Fisher Clinical Services GmbH ORG-100017323
|
Weil Am Rhein, Germany | Code 14, Other |
| Telerx Marketing Inc. ORG-100042319
|
Horsham, United States | Other, Code 8 |
| Neogenomics Laboratories Inc. ORG-100041804
|
Aliso Viejo, United States | Laboratory analysis |
| 4G Clinical B.V. ORG-100044721
|
Amsterdam, Netherlands | Interactive response technologies (IRT) |
Locations
5 EU/EEA countries · 13 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ended | 2 | 1 |
| Germany | Ended | 2 | 1 |
| Italy | Ongoing, recruitment ended | 10 | 4 |
| Norway | Ended | 6 | 2 |
| Spain | Ended | 14 | 5 |
| Rest of world
Canada, United Kingdom, Australia, United States, Turkey
|
— | 92 | — |
Investigational sites
Medical University Of Vienna
Department of Clinical Pharmacology, Waehringer Guertel 18-20, Alsergrund, Vienna
Universitaetsklinikum Essen AöR
Klinik für Hämatologie und Stammzelltransplantation, Hufelandstrasse 55, Holsterhausen, Essen
Azienda Sanitaria Universitaria Giuliano Isontina
SC UCO Ematologia, Via Costantino Costantinides 2, 34128, Trieste
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Oncologia Medica, Via Piero Maroncelli 40, 47014, Meldola
Azienda Ospedaliero-Universitaria Maggiore Della Carita
SCDU Ematologia, Corso Giuseppe Mazzini 18, 28100, Novara
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Ematologia, Via Francesco Sforza 28, 20122, Milan
St. Olavs Hospital HF
Hematology, P. O. Box 3250, Torgarden, Trondheim
Sykehuset Oestfold HF Kalnes
Hematology, Kalnesveien 300, 1714, Graalum
University Hospital Virgen Del Rocio S.L.
Hematology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital General Universitario Gregorio Maranon
Hematology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital General Universitario Morales Meseguer
Hematology, Avenida Del Marques De Los Velez S/n, 30008, Murcia
Hospital Del Mar
Hematology, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
Hospital Universitario De Burgos
Hematology, Avenida De Las Islas Baleares 3, 09006, Burgos
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2024-05-15 | 2024-08-07 | |||
| Germany | 2024-07-05 | ||||
| Italy | 2024-06-08 | 2024-10-21 | 2025-06-12 | ||
| Norway | 2024-05-17 | 2024-08-22 | |||
| Spain | 2024-05-17 | 2025-11-05 | 2024-06-10 | 2025-06-12 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 54 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-507067-19_redacted | 5.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Procedure | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Brochure | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Brochure | 2.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Patient Brochure | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Brochure | 2.1 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Brochure | 2.0 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Flyer | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Flyer | 2.0 |
| Recruitment arrangements (for publication) | K2_Recruitment material_Patient Flyer | 2.00 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Flyer | 2.1 |
| Recruitment arrangements (for publication) | K2_Recruitment Material_Patient Flyer | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF_Site contact details list | 1 |
| Subject information and informed consent form (for publication) | L1_Patient facing document statement | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main_redacted | 8.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional Sample Storage for Future Research | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional Sample Storage for Future Research | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional Sample Storage for Future Research | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Participant_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Participant_Redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_redacted | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_redacted | 4.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_redacted | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_redacted | 4.00 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnant Partner_redacted | 4.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Privacy_redacted | 7.0 |
| Subject information and informed consent form (for publication) | L2_ICF_Patient reimbursement_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L2_Participant Card | 2.0 |
| Subject information and informed consent form (for publication) | L2_Participant Card | 2.0 |
| Subject information and informed consent form (for publication) | L2_Participant Card | 2.0 |
| Subject information and informed consent form (for publication) | L2_Participant Card | 2.0 |
| Subject information and informed consent form (for publication) | L2_Participant Card_NO | 2.0 |
| Subject information and informed consent form (for publication) | L2_Patient Card Reimbursement | N/A |
| Subject information and informed consent form (for publication) | L2_Pocket Card_SOA | 2.0 |
| Subject information and informed consent form (for publication) | L2_Pocket Card_SOA | 2.0 |
| Subject information and informed consent form (for publication) | L2_Pocket Card_SOA | 2.0 |
| Subject information and informed consent form (for publication) | L2_Pocket Card_SOA | 2.0 |
| Subject information and informed consent form (for publication) | L2_Pocket Card_SOA | 2.0 |
| Subject information and informed consent form (for publication) | L2_Registration Form Reimbursement | N/A |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_German_2023-507067-19 | 5.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_Italian_2023-507067-19 | 5.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_Norwegian_2023-507067-19 | 5.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_Spanish_2023-507067-19 | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_German_2023-507067-19-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Italian_2023-507067-19-00_redacted | 5.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Spanish_2023-507067-19_redacted | 5.0 |
Application history
11 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-11-30 | Spain | Acceptable with conditions 2024-04-15
|
2024-04-15 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-05-17 | Acceptable with conditions 2024-04-15
|
2024-05-17 | |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2024-05-21 | Spain | Acceptable with conditions 2024-04-15
|
2024-05-21 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2024-07-02 | Acceptable with conditions 2024-04-15
|
2024-07-02 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2024-07-17 | Acceptable with conditions 2024-04-15
|
2024-07-17 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-6 | 2024-07-18 | Acceptable with conditions 2024-04-15
|
2024-07-18 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-24 | Spain | Acceptable 2025-02-04
|
2025-02-04 |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-7 | 2025-02-14 | Acceptable 2025-02-04
|
2025-02-14 | |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-8 | 2025-03-14 | Spain | Acceptable 2025-02-04
|
2025-03-14 |
| 10 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-27 | Spain | Acceptable 2025-08-26
|
2025-08-27 |
| 11 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-09-30 | Spain | Acceptable 2026-01-15
|
2026-01-19 |