Double-blind (neither the patient nor the doctor knows treatment allocation of the patient), randomized, placebo-controlled, prospective phase III clinical study to evaluate the efficacy and safety of Panzyga in infection prevention in patients with a specific type of cancer, cancer of the blood and bone marrow (Chronic Lymphocytic Leukemia) ("PRO-SID" study).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Aug 2020 → 19 Sep 2025

Decision date (initial)

2024-03-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Octapharma Pharmazeutika Produktionsges.m.b.H.

External identifiers

EU CT number

2023-509737-39-00

EudraCT number

2019-004375-40

WHO UTN

U1111-1299-6986

ClinicalTrials.gov

NCT04502030

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Prophylaxis, Pharmacoeconomic, Safety

The primary objective of this study is to demonstrate the benefit of Panzyga administration compared with placebo as primary infection prophylaxis in CLL patients with secondary
immunodeficiency (SID) undergoing CLL antineoplastic therapy.

Secondary objectives 1

1. The secondary objectives of this study are to compare the following aspects in CLL patients with SID treated with and without primary Panzyga prophylaxis: - Overall infection rate - Frequency of prophylaxis with anti-infectives (antibacterials and antivirals) - Duration of prophylaxis with anti-infectives (antibacterials and antivirals)

Conditions and MedDRA coding

Primary infection prophylaxis in patients with chronic lymphocytic leukemia (CLL) and secondary hypogammaglobulinemia.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. Treatment-naïve or relapsed/refractory CLL patients undergoing CLL antineoplastic treatment. Diagnosis of B-cell CLL established according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and documented within medical records.
2. 2. Hypogammaglobulinemia (IgG levels <5 g/L) as confirmed by the Central Laboratory.
3. 3. ≥18 years of age.
4. 4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted.

Exclusion criteria 20

1. 1. IgG treatment within 3 months prior to Screening.
2. 10. Female patients of childbearing potential unwilling to use a protocol-required method of contraception (as per protocol section 7.3.9 b) from the Screening Visit throughout the study treatment period and for 30 days following the last dose of study drug.
3. 11. Human immunodeficiency virus (HIV) infection at Screening (defined for the study as positive HIV antibody test).
4. 12. Patients found to be chronic carriers of hepatitis B virus (HBV), defined by positive surface antigen (HBsAg), positive Hepatitis B core antibodies (HBcAb) and/or low HBV titers, who will not receive targeted antiviral therapy while undergoing CLL therapy, and patients with active HBV, defined as high HBV titers.
5. 13. Uncontrolled hepatitis C infection at Screening (defined for the study as positive hepatitis virus C (HCV) polymerase chain reaction (PCR)).
6. 2. Antibiotic prophylaxis and/or treatment within 7 days prior to Baseline (with the exception of trimethoprim-sulfamethoxazole (TMP/SMX), diaminodiphenyl sulfone [dapsone] and pentamidine inhalation).
7. 3. Current major infection or >1 major infection in the previous 6 months before Baseline.
8. 4. History of anaphylaxis or severe systemic response to immunoglobulin, blood or plasma-derived products or any Panzyga component.
9. 5. History of a non-CLL malignancy or other medical condition with life-expectancy of less than two years.
10. 6. Severe liver disease, with signs of ascites and/or hepatic encephalopathy.
11. 7. Severe kidney disease (as defined by estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2).
12. 8. Body weight >140 kg.
13. 9. Eastern Cooperative Oncology Group (ECOG) performance score of >2 (Appendix1).
14. 14. Pregnant and lactating women.
15. 15. Subjects with a history of thromboembolic events (TEE) such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) within 6 months before Baseline.
16. 16. Planned or ongoing immunosuppressive treatment (other than for CLL or corticosteroids) or other forbidden medication during the entire study duration after study enrollment.
17. 17. Participation in another interventional clinical trial that is either blinded or involves an investigational (not approved) product within 3 months before Baseline or during the course of the clinical study. Participation in observational clinical trials or open-label trials involving an approved product may be permitted after consultation with the medical monitor.
18. 18. Known IgA deficiency with antibodies to IgA (as part of the patient´s medical history).
19. 19. Known blood hyperviscosity, or other hypercoagulable states.
20. 20. Patients unable or unwilling to understand or comply with the study protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Since the study objective is to show the benefit of Panzyga administration as primary infection prophylaxis, the primary endpoint is not the major infection rate but occurrence of at least one major infection in CLL patients with or without primary infection prophylaxis with Panzyga. Please refer to the Protocol for more information on the Primary endpoint.

Secondary endpoints 3

1. 1. Overall infection rate: infection rate for all infections.
2. 2. Frequency of prophylaxis with anti-infectives (antibacterials and antivirals).
3. 3. Duration of prophylaxis with anti-infectives (antibacterials and antivirals).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Sponsor organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Address

Oberlaaer Strasse 235, Favoriten Favoriten

City

Vienna

Postcode

1100

Country

Austria

Scientific contact point

Organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Contact name

Global Clinical Project Manager

Public contact point

Organisation

Octapharma Pharmazeutika Produktionsgesellschaft mbH

Contact name

Global Clinical Project Manager

Third parties 9

Locations

7 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications