A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)

Cold Agglutinin Disease Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05096403
• Other study ID #: Sobi.PEGCET-101
• Status: Suspended
• Phase: Phase 3
• Start date: October 20, 2022
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the efficacy of pegcetacoplan administration compared to placebo in increasing hemoglobin (Hgb) level from baseline and avoiding transfusion in participants with primary cold agglutinin disease (CAD).

Description:

This is a blind (actual treatment not disclosed to Investigator or participant) study to study pegcetacoplan in people with cold agglutinin disease. The study will consist of a 4-week screening period where selected tests will be conducted to ensure that the patient is eligible to participate in the study, followed by Part A, a 24-week blinded treatment period where the participants will receive either pegcetacoplan or a placebo treatment, looking like pegcetacoplan but with no effect. After this period, the participants will move into Part B, a 24-week period where they will all receive pegcetacoplan. Part C is a 48-week maintenance period with pegcetacoplan for all participants. After the end of treatment participants will undergo a safety follow visit about 8 weeks after last dose. All eligible study participants will receive pegcetacoplan or placebo treatment, administered via subcutaneous infusion twice a week at home. The subcutaneous infusion requires two small needles to be inserted into the fatty layer of tissue under the skin and the investigational medication will flow into the body. Study participants and/or caregivers will be trained on home administration of pegcetacoplan.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 57
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years or older.

2. Diagnosis of primary CAD.

3. Hb level = 9 g/dL.

4. Documented results from bone marrow biopsy within 1 year of screening

5. Either have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (Types A, C, W, Y, and B), and Haemophilus influenzae (Type B) within 2 years prior to screening or agree to receive vaccination during screening.

6. Women of childbearing potential (WOCBP), defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last IMP dose.

7. Men must agree to the following for the duration of the study and 8 weeks after their

last IMP dose:

1. Avoid fathering a child.

2. Use protocol-defined methods of contraception.

3. Refrain from donating sperm.

8. Willing and able to give written informed consent.

Exclusion Criteria:

1. Have received other anti-complement therapies (approved or investigational) within 5 half-lives of the agent prior to randomization.

2. Treatment with rituximab monotherapy within 12 weeks prior to randomization, or rituximab combination therapies (e.g., with bendamustine, fludarabine, other cytotoxic drugs or ibrutinib) within 16 weeks prior to randomization.

3. Diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies.

4. History of an aggressive lymphoma or presence of a lymphoma requiring therapy.

5. Have received an organ transplant.

6. Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection.

7. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) > 2.5 x ULN, or direct bilirubin levels > 2 x ULN.

8. Inability to cooperate with study procedures.

Related Conditions & MeSH terms

• Anemia, Hemolytic, Autoimmune
• Cold Agglutinin Disease

Intervention

Drug:
• Pegcetacoplan
Pegcetacoplan taken twice weekly as subcutaneous injection

Locations

Country	Name	City	State
Austria	Medical University	Vienna
Belgium	Algemeen Ziekenhuis Klina	Brasschaat
Belgium	UZ Gasthuisberg	Leuven
Belgium	CHU de Liège	Liège
Canada	St. Michael's Hospital	Toronto
Finland	Helsinki University Hospital - Comprehensive Cancer Center	Helsinki
Georgia	"LTD Medinvest Institute of Hematology and Transfusiology "	Tbilisi
Georgia	Ltd M. Zodelava Hematology Centre	Tbilisi
Germany	Universitätsklinikum Essen Klinik f. Hämatologie - Westdeutsches Tumorzentrum	Essen
Germany	Institut f. Transfusionsmedizin - Universität Ulm	Ulm
Hungary	Semmelweis Egyetem	Budapest
Italy	A.O.R.N. S.G. Moscati di Avellino	Avellino
Italy	ASST degli Spedali Civili di Brescia_Presidio Ospedaliero di Brescia_U.O. Ematologia	Brescia
Italy	"FOND IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	AOU Maggiore della Carità SCDU Ematologia	Novara
Italy	Azienda Ospedaliera Ospedali Riuniti ""Villa Sofia-Cervello	Palermo
Italy	Grande Ospedale Metropolitano ""Bianchi - Melacrino - Morellii	Reggio Calabria
Japan	Fukushima Medical University Hospital	Fukushima
Japan	University of Tsukuba Hospital	Ibaraki
Japan	Ishikawa Prefectural Central Hospital	Kanazawa
Japan	Aichi Medical University Hospital	Nagakute
Japan	Shinshu University Hospital	Nagano
Japan	Osaka University Hospital	Osaka
Netherlands	Amsterdam UMC	Amsterdam
Norway	Haukeland University Hospital	Bergen
Norway	Sykehuset Østfold Kalnes	Grålum
Norway	St Olavs Hospital, Avdeling for blodsykdommer	Trondheim
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario de Gran Canaria Dr. Negrin	Las Palmas De Gran Canaria
Spain	Hospital Clínico Universitario de Salamanca	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario y Politecnico La Fe	Valencia
United Kingdom	St James' University Hospital	Leeds
United Kingdom	Cancer Clinical Trials Unit, Haematology -University College London -	London
United Kingdom	Royal London Hospital	London
United Kingdom	Russell Centre for Clinical Haematology	Nottingham
United Kingdom	Churchill Hospital	Oxford
United States	East Carolina University Division of Hematology/ Oncology	Greenville	North Carolina
United States	University of Iowa Hospitals & Clinics - The Hemophilia Treatment Center (HTC)	Iowa City	Iowa
United States	Lakes Research	Miami Lakes	Florida
United States	Weill Cornell Medicine / NewYork Presbyterian Hospital	New York	New York
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Finland,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Netherlands,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response (R)	A participant will be considered to have a response if the Hgb level increases greater than or equal to (>=) 1.5 gram per deciliter (g/dL) from baseline and this increase is maintained from Week 16 through Week 24 in absence of blood transfusion from Week 5 through Week 24.	Week 24
Secondary	Change from Baseline to Week 24 in Hemoglobin (Hgb) level.	Mean change from Baseline to Week 24 in Hemoglobin (Hgb) level will be assessed	Week 24
Secondary	Transfusion avoidance from Week 5 to Week 24	Percentage of patients who did not received a blood transfusion between Week 5 and Week 24 will be assessed	Week 24
Secondary	Change From Baseline to Week 24 in Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) Scale Score (Quality of Life)	FACT-An consists consists of 33 questions related to general quality of life and to the impact of fatigue and other anemia-related symptoms assessed using a 5 point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question are added to obtain a total score.	Week 24
Secondary	Number of PRBC transfusions from Week 5 to Week 24.	Number of blood transfusions received between Week 5 and Week 24 will be assessed	Week 24
Secondary	Change from Baseline to Week 24 in markers of hemolysis	Mean change from baseline to Week 24 in Lactate dehydrogenase (LDH) level; Haptoglobin level; Indirect bilirubin level; Absolute reticulocyte counts (ARC).	Week 24
Secondary	Normalization of markers of hemolysis at Week 24	Percentage of patients with LDH level; Indirect bilirubin level and ARC within normal ranges.	Week 24
Secondary	Change From Baseline to Week 24 in 12-item short form survey (SF-12)	SF-12 health survey is a self-reported questionnaire to measure participant's profile of functional health and well-being. It includes 12 questions.	24 weeks
Secondary	Change From Baseline to Week 24 in five level EuroQol five dimensions questionnaire (EQ-5D-5L)	The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. A scale with score 0-100 is used to collect response on current health status.	Week 24