PRISM: Efficacy and Safety Study of I10E in Treatment of Patients With CIDP

• Sponsor: Laboratoire français de Fractionnement et de Biotechnologies (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02293460
• Collaborator: (none)
• Enrollment: 44
• Locations: 33
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary objective:

To assess the efficacy of I10E in improving the disability of patients with CIDP.

Secondary objective:

To assess the safety of I10E in patients with CIDP.

Condition or Disease	Intervention/Treatment	Phase
Chronic Inflammatory Demyelinating Polyradiculoneuropathy	Drug: I10E	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An International, Multicentre, Efficacy and Safety Study of I10E in Initial and Maintenance Treatment of Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Sep 29, 2017
• Actual Study Completion Date: Sep 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I10E Arm	Drug: I10E; Patients who meet all eligibility criteria will receive one dose of IMP at 2g/kg over 2-5 days followed by 7 doses of IMP at 1g/kg over 1-2 day(s), every 3 weeks. Duration of treatment period: 21 weeks +/- 7 days.

Outcome Measures

Primary Outcome Measures

1. Efficacy Endpoint: Responder Rate at End of Study [24 weeks after first treament injection]

   Responders were defined as patients with a decrease ≥1 point in the adjusted INCAT disability score compared to baseline. Adjusted INCAT disability score can vary from 0 (normal) to 9 (maximal disability). If a patient was treated with a not-allowed treatment during the study period, then all adjusted INCAT disability score measured after the intake of these not-allowed treatments were censored. If the score at EoS visit was missing, then the Last Observation Carried Forward (LOCF) approach was applied to replace this missing value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female patient aged 18 years or more

2. Definite or probable CIDP according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines 2010 clinical and neurophysiological criteria Pure motor CIDP, provided that a diagnosis of multifocal motor neuropathy has been ruled out CIDP associated with monoclonal gammopathy of undetermined significance (MGUS), provided that anti-MAG antibodies titer is lower than the used technique's negativity threshold (1000 BTU for Bühlmann ELISA technique) Lewis-Sumner syndrome

3. Score of at least 2 on the adjusted INCAT disability scale

4. Patient who either :

5. has never been previously treated with Ig (Ig-naive patient) Or

6. was previously treated with Ig but is in clinical relapse following treatment withdrawal. In the latter case, the last Ig course shall have been administered no less than 3 months prior to screening

Exclusion Criteria:

1. History of IgA deficiency, unless the absence of anti-IgA antibodies has been documented

2. History of cardiac insufficiency (New York Heart Association [NYHA] III/IV), uncontrolled cardiac arrhythmia, unstable ischemic heart disease, or uncontrolled hypertension

3. History of venous thrombo-embolic disease, myocardial infarction or, cerebrovascular accident

4. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematologic malignancy with monoclonal gammopathy

5. Body mass Index (BMI) ≥40 kg/m²

6. Glomerular filtration rate <80 mL/min/1.73m² measured according to the Modified Diet in Renal Disease (MDRD) calculation

7. Any other ongoing disease that may cause chronic peripheral neuropathy, such as toxin exposure, dietary deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus erythematosus or other connective tissue diseases, infection with HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV), Lyme disease, multiple myeloma, Waldenström's macroglobulinaemia, amyloid, and hereditary neuropathy

8. Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception.

9. Any other serious medical condition that would interfere with the clinical assessment of CIDP or use of I10E or prevent the patient from complying with the protocol requirements

10. Increasing dosage or introduction of a corticotherapy within the last 3 months prior to screening, with oral or systemic corticosteroids at a dose higher than 10 mg daily prednisolone or equivalent. Topical corticosteroids are permitted

11. Treatment within 12 months prior to screening with immunomodulatory or immunosuppressant agents (including but not limited to cyclophosphamide, cyclosporine, interferon-alfa, interferon-beta1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil, methotrexate and haemopoetic stem cell transplantation)

12. Plasma exchange, blood products or derivatives administered within the last 3 months prior to screening

13. Administration of another investigational product within the last month prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU de Bordeaux - Hôpital Pellegrin	Bordeaux		France
2	Hôpital général du CHU de Dijon	Dijon		France
3	CHU de Nice - Hôpital l'Archet	Nice		France
4	CHU Paris - Hôpital Pitié salpétrière	Paris		France
5	Hôpital Pontchaillou	Rennes		France
6	CHU de saint Etienne - Hôpital nord	Saint Etienne		France
7	Hôpital de Hautepierre	Strasbourg		France
8	IRRCS Azienda Ospedaliera Universitaria	Genova		Italy
9	IRCCS - Istituto Clinico Humanitas	Milano		Italy
10	IRRCS Istituto Nazionale Neurologico Besta	Milano		Italy
11	Ospedale San Raffaele IRCCS	Milano		Italy
12	Azienda Ospedaliere Universitaria di Padova	Padova		Italy
13	Università Cattolica del Sacro Cuore	Roma		Italy
14	Azienda Ospedaliere Universitaria san Giovanni	Torino		Italy
15	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain
16	Hospital Quiron Madrid	Madrid		Spain	28223
17	Hospital General Universitario Gregorio	Madrid		Spain
18	Hospital clinico Universitario de Santiago	Santiago de Compostela		Spain
19	Hospital Universitario Virgen del Rocio	Seville		Spain
20	Hospital Universitario i Politècnico La Fe	Valencia		Spain
21	Hôpital Razi, La Manouba	Manouba		Tunisia
22	Hôpital Fattouma Bourguiba	Monastir		Tunisia
23	Hôpital habib Bourguiba	Sfax		Tunisia
24	Hôpital Sahloul	Sousse		Tunisia
25	Hôpital militaire de Tunis	Tunis		Tunisia
26	Ankara University medical School Neurology	Ankara		Turkey
27	Hacettepe University Medical School Neurology	Ankara		Turkey
28	Uludag University Medical School Neurology	Bursa		Turkey
29	Istanbul UniversityCerrahpasa Medical School Neurology	Istanbul		Turkey
30	Marmara Universitesi Egitim Ve Arastirma Hastanesi	Istanbul		Turkey
31	St Georges	London		United Kingdom	SW17OQT
32	Southampton General Hospital	Southampton		United Kingdom
33	University Hospital of North Straffordshire	Stratford-upon-Avon		United Kingdom

Sponsors and Collaborators

• Laboratoire français de Fractionnement et de Biotechnologies

Investigators

• Principal Investigator: Eduardo NOBILE-ORAZIO, MD, IRCCS Instituto Clinico Humanitas, Milano, Italy

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 7, 2018
• Study Protocol - May 3, 2017

More Information

Publications

None provided.

• Responsible Party: Laboratoire français de Fractionnement et de Biotechnologies
• ClinicalTrials.gov Identifier: NCT02293460
• Other Study ID Numbers: I10E-1302
• First Posted: Nov 18, 2014
• Last Update Posted: Jan 27, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Laboratoire français de Fractionnement et de Biotechnologies: Peripheral neuropathy; Disimmune disease; Neurology Chronic disease; Rare disease
• Additional relevant MeSH terms: Polyradiculoneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Study Results

Participant Flow

Recruitment Details	Between 24 February 2015 and 22 March 2017, 59 subjects from 23 sites signed an informed consent.
Pre-assignment Detail	59 subjects signed an informed consent in the pre-assigment period. Among them, 18 subjects were considered as a screening failure including 3 subjects re-screened and finally enrolled. Of 44 enrolled subjects, on subject was discontinued (consent withdrawn by subject) from the study before the first administration of study drug.

Arm/Group Title	Single Arm
Arm/Group Description	This study included patients never previously treated with IgG and patients already treated with IgG but in clinical relapse following IgG therapy discontinuation.
Period Title: Overall Study
STARTED	43
COMPLETED	37
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Total Treated Set
Arm/Group Description	All subjects who received at least one infusion of I10E
Overall Participants	43
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 74.4%
>=65 years	11 25.6%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50.0
Sex: Female, Male (Count of Participants)
Female	19 44.2%
Male	24 55.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	24 55.8%
More than one race	0 0%
Unknown or Not Reported	19 44.2%
Region of Enrollment (participants) [Number]
Turkey	2 4.7%
Italy	16 37.2%
United Kingdom	1 2.3%
France	2 4.7%
Tunisia	8 18.6%
Spain	6 14%
Poland	8 18.6%

Outcome Measures

1. Primary Outcome

Title	Efficacy Endpoint: Responder Rate at End of Study
Description	Responders were defined as patients with a decrease ≥1 point in the adjusted INCAT disability score compared to baseline. Adjusted INCAT disability score can vary from 0 (normal) to 9 (maximal disability). If a patient was treated with a not-allowed treatment during the study period, then all adjusted INCAT disability score measured after the intake of these not-allowed treatments were censored. If the score at EoS visit was missing, then the Last Observation Carried Forward (LOCF) approach was applied to replace this missing value.
Time Frame	24 weeks after first treament injection

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Full Analysis Set
Arm/Group Description	All TTS subjects having an available assessment of the primary efficacy criteria.
Measure Participants	42
Count of Participants [Participants]	32 74.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Full Analysis Set
	Comments	For this single-arm study, the response rate was tested against the historical response rate of 33.3% with a 1-sided Clopper-Pearson exact test at the nominal level of significance of 2.5% on the Full Analysis Set. The null and alternative hypotheses were as follows: H0: pI10E <= 33.3% H1: pI10E > 33.3%
	Type of Statistical Test	Superiority
	Comments	The response rate was tested against the historical response rate of 33.3%.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided test at nominal level of significance alpha = 2.5 %
	Method	exact binomial Clopper-Pearson
	Comments
Method of Estimation	Estimation Parameter	Responder rate
	Estimated Value	76.2
	Confidence Interval	(2-Sided) 95%; 60.5 to 87.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	The safety was assessed by recording all AEs occurring during the study, i.e. after signature of the informed consent and until the end of the study recorded (week 24 after inclusion).
Arm/Group Title	Total Treated Set
Arm/Group Description	All subjects who received at least one infusion of I10E
All Cause Mortality
	Total Treated Set
	Affected / at Risk (%)	# Events
Total	0/43 (0%)
Serious Adverse Events
	Total Treated Set
	Affected / at Risk (%)	# Events
Total	7/43 (16.3%)
Blood and lymphatic system disorders
Neutropenia	1/43 (2.3%)	1
Gastrointestinal disorders
Pancreatitis	1/43 (2.3%)	1
Immune system disorders
Anaphylactic reaction	1/43 (2.3%)	1
Injury, poisoning and procedural complications
Femur fracture	1/43 (2.3%)	1
Synovial rupture	1/43 (2.3%)	1
Investigations
Fibrin D dimer increased	1/43 (2.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal adenocarcinoma	1/43 (2.3%)	1
Nervous system disorders
Headache	1/43 (2.3%)	1
Transient ischaemic attack	1/43 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Total Treated Set
	Affected / at Risk (%)	# Events
Total	39/43 (90.7%)
Blood and lymphatic system disorders
Anaemia	3/43 (7%)	3
Ear and labyrinth disorders
Vertigo	3/43 (7%)	5
Gastrointestinal disorders
Nausea	5/43 (11.6%)	6
General disorders
Pyrexia	8/43 (18.6%)	11
Asthenia	4/43 (9.3%)	4
Chills	3/43 (7%)	10
Malaise	3/43 (7%)	5
Infections and infestations
Influenza	8/43 (18.6%)	10
Urinary tract infection	5/43 (11.6%)	5
Musculoskeletal and connective tissue disorders
Myalgia	5/43 (11.6%)	5
Arthralgia	4/43 (9.3%)	6
Nervous system disorders
Headache	20/43 (46.5%)	79
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/43 (7%)	3
Skin and subcutaneous tissue disorders
Pruritus	3/43 (7%)	4
Rash	3/43 (7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.