Pembrolizumab in progressive multifocal leukoencephalopathy (PML) in immunocompromised patients without HIV infection (PENALTY)

Start 15 Jan 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 10 sites · Protocol APHP211001

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruiting

Participants planned 33

Countries 1

Sites 10

Immunocompromised patients with PML (with an underlying cause of immunosuppression hardly reversible, i.e. not the patients with HIV nor those receiving biologics for chronic inflammatory diseases).

To assess the efficacy of Pembrolizumab in terms of at least one negativation of JCV viral load in cerebrospinal fluid (CSF) within the M0 to M3 period, in immunocompromised patients with PML (with an underlying cause of immunosuppression hardly reversible, i.e. not the patients with HIV nor those receiving biologics f…

Key facts

Sponsor: Assistance Publique Hopitaux De Paris
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Virus Diseases [C02]
Trial duration: 15 Jan 2025 → ongoing
Decision date (initial): 2023-10-24
Transition trial: No
Low-intervention: No
Rare-disease indication: Yes
Vulnerable population: Yes
Funding sources: DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Secondary objectives 10

1. Cumulative incidence of negativation of JCV viral load in the CSF (death as a competing event)
2. Evolution of the JCV viral load in CSF
3. In patients achieving negativation of JCV viral load in CSF, cumulative incidence of repositivation of JCV PCR in CSF
4. Evolution of neurological status assessed by the use of NIH Stroke Scale (NIHSS)
5. Evolution of disability and outcome measured by modified Rankin Scale
6. Evolution of disability and outcome measured by Glasgow Outcome Scale Extended (GOS-E)
7. Relapse after improvement or progression (adjudicated by an adjudication committee)
8. Survival rate at M12
9. Cause- specific (i.e. related to PML or not) survival rate
10. Adverse events

Conditions and MedDRA coding

Immunocompromised patients with PML (with an underlying cause of immunosuppression hardly reversible, i.e. not the patients with HIV nor those receiving biologics for chronic inflammatory diseases).

Version	Level	Code	Term	System organ class
20.0	SOC	10021881	Infections and infestations	1
20.1	PT	10036807	Progressive multifocal leukoencephalopathy	100000004862

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years old
2. Diagnosis of definite PML since less than 2 months according to American Academy of Neurology
3. Presence of JCV in the CSF in the last CSF sampling.
4. Signed informed consent (from the patient, or if unable to consent, from a surrogate)
5. For women of childbearing potential: negative serum or urine b-HCG test and agree to use a highly effective contraception methods during 8 months (i.e. until 6 months after end of experimental treatment)

Exclusion criteria 12

1. Patients in whom immune reconstitution is achievable (HIV infection - Multiple sclerosis - Auto-immune and inflammatory diseases)
2. Patients who have received solid organ transplantation
3. Hypersensitivity to the active substance or to any of the excipients
4. Life expectancy less than 1 month
5. Pregnancy or lactating women or planning birth during the study period
6. Having previously been treated by anti-PD1mAb
7. Patient receiving IL-2 or IL-7 for the treatment of PML at inclusion
8. Patient whose weight is > 100kg
9. Participation in other interventional study [a patient already included in another interventional study for which the treatment can lead to an immunodepression can be included if: - the investigational treatment has been completed and there is no risk of drug interaction with the administration of Pembrolizumab as defined in PENALTY study - if this does not alter the study's ability to evaluate the effect of Pembrolizumab in terms of safety and efficacy (from the investigator's point of view)]
10. Patient without national health insurance, and patient on AME (state medical aid)
11. Patient under guardianship or curatorship
12. Patient deprived of their liberty by a judicial or administrative decision

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Negativation of JCV viral load in the CSF as assessed by PCR: at least one JCV PCR in the CSF negative in the M0 to M3 period (lumbar punctures and JCV PCR on CSF at D0, M1, M2 and M3 are part of usual care). Patients dying before negativation of JCV PCR will be considered as failure (i.e. absence of negativation)

Secondary endpoints 10

. Negativation of JCV PCR viral load in the CSF: cumulative incidence of negative JCV viral load measures by PCR in CSF, with death as competing event (cannot be primary outcome as we have no data to estimate the sample size adequately)
2. Evolution of the JCV viral load in the CSF (repeated measures JCV PCR in CSF)
3. Repositivation of JCV PCR: at least a positive result following at least a negative result
4. NIH Stroke Scale (NIHSS): measure of neurological status at M1, M2, M3, M6 and M12
5. Modified Rankin Scale (includes death as most severe state): measure the degree of disability or dependence in the daily activities in neurological conditions at M1, M2, M3, M6 and M12
6. Glasgow Outcome Scale Extended (GOS-E): measure of neurological outcome and degree of disability in neurological conditions at M1, M2, M3, M6 and M12
7. Relapse or progression (adjudication committee with infectious diseases specialists, neurologists, hematologists, intensivists, and neuroradiologists experienced in PML; on the basis of clinical evolution, JCV PCR in CSF, brain MRI)
8. Death (and date of death)
9. Cause specific death: death related to PML (adjudication committee).
10. Any adverse event classified by using US NCI CTCAE

Investigational products

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

Test 1

Pembrolizumab

SUB167136 · Substance

Active substance: Pembrolizumab
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INJECTION
Route of administration: INTRAVENOUS
Max daily dose: 200 mg milligram(s)
Max total dose: 600 mg milligram(s)
Max treatment duration: 2 Month(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation: Assistance Publique Hopitaux De Paris
Address: Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City: Paris Cedex 10
Postcode: 75475
Country: France

Scientific contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Pr Valérie POURCHER

Public contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Carla Vandenabele

Locations

1 EU/EEA country · 10 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruiting	33	10
Rest of world	—	0	—