PRISM2: Efficacy and Safety Study of I10E in the Maintenance Treatment of Patients With CIDP: Extension of PRISM Study I10E-1302

• Sponsor: Laboratoire français de Fractionnement et de Biotechnologies (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02317562
• Collaborator: (none)
• Enrollment: 19
• Locations: 30
• Arm: 1
• Duration (Months): 20.9
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary objective:

To assess the efficacy of I10E administered at a reduced maintenance dose in sustaining CIDP response after an initial 6-month treatment in PRISM study. (I10E-1302).

Secondary objective:

To assess the safety of I10E in this patient population.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: International, Multicentre, Efficacy and Safety Study of I10E in the Maintenance Treatment of Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Extension of PRISM Study I10E-1302"
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Jul 28, 2017
• Actual Study Completion Date: Jul 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I10E Arm	Drug: I10E; Patients who met all eligibility criteria will receive 0.5 g/kg of IMP every 3 weeks during 45 weeks.

Outcome Measures

Primary Outcome Measures

1. Efficacy Endpoint : Responder Rate at End of Study (EOS) Visit [week 48 (End-of-Study)]

   Since the study was prematurely terminated and an important number of subjects early withdrawn, the responder rate is biased and consequently not interpretable. Responders were defined as subjects with either: No change or decrease in the adjusted INCAT disability score and without any change in CIDP treatment between baseline and EOS visit. OR An increase by 1 point in the adjusted INCAT disability score without requirement of any change in CIDP treatment between baseline and EOS visit.

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. Responder patient who have completed the last visit of PRISM I10E-1302 study defined as a patient with a decrease ≥1 point in the adjusted INCAT disability score between baseline and the end-of-study (EOS) visit of PRISM I10E-1302 study.

3. Covered by national healthcare insurance system as required by local regulations.

4. Written informed consent obtained prior to any study-related procedures.

Exclusion Criteria:

1. History of severe allergic reaction or serious adverse reaction to any Ig.

2. Known hypersensitivity to human Ig or to any of the excipients of I10E (glycine and polysorbate 80).

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

4. History of venous thromboembolic disease, myocardial infarction or cerebrovascular accident.

5. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematological malignancy with monoclonal gammopathy.

6. Body mass index (BMI) ≥40 kg/m².

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

8. 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, amyloidosis, and hereditary neuropathy.

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

10. 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.

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

12. Treatment within 12 months prior to screening with immunomodulatory or immunosuppressant agents (including but not limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil and methotrexate) or haemopoetic stem cell transplantation.

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

14. Anticipated poor compliance of patient with study procedures.

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	CHU de Saint Etienne - Hôpital Nord	Saint Etienne		France
6	Hôpital de Hautepierre	Strasbourg		France
7	IRRCS Azienda Ospedaliera Universitaria	Genova		Italy
8	IRCCS Instituto Clinico Humanitas	Milano		Italy
9	IRRCS Istutito Nazionale Neurologico Besta	Milano		Italy
10	Ospedale San Raffaele IRCCS	Milano		Italy
11	Azienda Ospedaliera Universitaria di Padova	Padova		Italy
12	Università Cattolica del sacro Cuore	Roma		Italy
13	Azienda Ospedaliera Universitaria san Giovanni	Torino		Italy
14	Hospital de la santa creu i Sant Pau	Barcelona		Spain
15	Hospital General Universitario Gregorio	Madrid		Spain
16	Hospital Clinico Universitario de Santiago	Santiago de Compostela		Spain
17	Hospital Universitario Virgen del Rocio	Seville		Spain
18	Hospital Universitario i Politècnico La Fe	Valencia		Spain
19	Tunisia Hôpital Razi	La Manouba		Tunisia
20	Hôpital Fattouma Bourguiba	Monastir		Tunisia
21	Hôpital Habib Bourguiba	Sfax		Tunisia
22	Hôpital Sahloul	Sousse		Tunisia
23	Hôpital Militaire de Tunis	Tunis		Tunisia
24	Ankara university medical school Neurology	Ankara		Turkey
25	Hacettepe University medical School Neurology	Ankara		Turkey
26	Uludag University Medical School Neurology	Bursa		Turkey
27	istanbul University Cerrahpasa Medical School Neurology	Istanbul		Turkey
28	Marmara Universitesi Egitim Ve Arastirma Hastanesi	Istanbul		Turkey
29	Southhampton general Hospital	Southhampton		United Kingdom
30	University Hospital of North Straffordshire	Straffordshire		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)

• Study Protocol - May 3, 2017
• Statistical Analysis Plan - Oct 30, 2017

More Information

Publications

None provided.

• Responsible Party: Laboratoire français de Fractionnement et de Biotechnologies
• ClinicalTrials.gov Identifier: NCT02317562
• Other Study ID Numbers: I10E-1306
• First Posted: Dec 16, 2014
• Last Update Posted: Apr 20, 2021
• Last Verified: Apr 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 09 November 2015 and 23 June 2017, 20 subjects from 14 sites signed an informed consent.
Pre-assignment Detail	20 subjects signed an informed consent but only 19 subjects enrolled (1 screening failure).

Arm/Group Title	I10E Arm
Arm/Group Description	Participation in the study was proposed to all subjects who completed and responded to treatment in PRISM study, satisfying in eligibility criteria and were willing to continue I10E at a reduced maintenance dose. Each subject was expected to receive 16 doses of I10E (study drug) at 0.5 g/kg over 1 to 2 days, every 3 weeks.
Period Title: Overall Study
STARTED	19
COMPLETED	5
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	I10E Arm
Arm/Group Description	Participation in the study was proposed to all subjects who completed and responded to treatment in PRISM study, satisfying in eligibility criteria and were willing to continue I10E at a reduced maintenance dose. Each subject was expected to receive 16 doses of I10E (study drug) at 0.5 g/kg over 1 to 2 days, every 3 weeks.
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 78.9%
>=65 years	4 21.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50.0
Sex: Female, Male (Count of Participants)
Female	7 36.8%
Male	12 63.2%
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	11 57.9%
More than one race	0 0%
Unknown or Not Reported	8 42.1%
Region of Enrollment (participants) [Number]
Turkey	1 5.3%
Italy	4 21.1%
United Kingdom	1 5.3%
France	2 10.5%
Tunisia	6 31.6%
Spain	2 10.5%
Poland	3 15.8%

Outcome Measures

1. Primary Outcome

Title	Efficacy Endpoint : Responder Rate at End of Study (EOS) Visit
Description	Since the study was prematurely terminated and an important number of subjects early withdrawn, the responder rate is biased and consequently not interpretable. Responders were defined as subjects with either: No change or decrease in the adjusted INCAT disability score and without any change in CIDP treatment between baseline and EOS visit. OR An increase by 1 point in the adjusted INCAT disability score without requirement of any change in CIDP treatment between baseline and EOS visit.
Time Frame	week 48 (End-of-Study)

Outcome Measure Data

Analysis Population Description

Study prematurely stopped due to sponsor decision based on the relapse rate.

Arm/Group Title	I10E Arm
Arm/Group Description	Participation in the study was proposed to all subjects who completed and responded to treatment in PRISM study, satisfying in eligibility criteria and were willing to continue I10E at a reduced maintenance dose. Each subject was expected to receive 16 doses of I10E (study drug) at 0.5 g/kg over 1 to 2 days, every 3 weeks.
Measure Participants	19
Count of Participants [Participants]	15 78.9%

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. (up to 48 weeks after inclusion).
Arm/Group Title	I10E Arm
Arm/Group Description	Participation in the study was proposed to all subjects who completed and responded to treatment in PRISM study, satisfying in eligibility criteria and were willing to continue I10E at a reduced maintenance dose. Each subject was expected to receive 16 doses of I10E (study drug) at 0.5 g/kg over 1 to 2 days, every 3 weeks.
All Cause Mortality
	I10E Arm
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	I10E Arm
	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)
Renal and urinary disorders
Urinary retention	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	I10E Arm
	Affected / at Risk (%)	# Events
Total	12/19 (63.2%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)	1
Cardiac disorders
Palpitations	1/19 (5.3%)	1
Ear and labyrinth disorders
Tinnitus	1/19 (5.3%)	1
Gastrointestinal disorders
Abdominal pain	1/19 (5.3%)	1
Diarrhoea	1/19 (5.3%)	1
Duodenal ulcer	1/19 (5.3%)	1
Gastritis	1/19 (5.3%)	1
Hiatus hernia	1/19 (5.3%)	1
Vomiting	1/19 (5.3%)	1
General disorders
Fatigue	2/19 (10.5%)	2
Chills	1/19 (5.3%)	1
Injection site erythema	1/19 (5.3%)	1
Injection site oedema	1/19 (5.3%)	1
Pain	1/19 (5.3%)	1
Pyrexia	1/19 (5.3%)	1
Infections and infestations
Conjunctivitis	1/19 (5.3%)	1
Gastroenteritis viral	1/19 (5.3%)	1
Infected bite	1/19 (5.3%)	1
Influenza	1/19 (5.3%)	2
Nasopharyngitis	1/19 (5.3%)	2
Tooth abscess	1/19 (5.3%)	1
Upper respiratory tract infection	1/19 (5.3%)	1
Urinary tract infection	1/19 (5.3%)	2
Injury, poisoning and procedural complications
Ligament sprain	1/19 (5.3%)	1
Post traumatic pain	1/19 (5.3%)	1
Investigations
Blood pressure increased	2/19 (10.5%)	2
Blood lactate dehydrogenase	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	3/19 (15.8%)	3
Arthralgia	2/19 (10.5%)	3
Back pain	2/19 (10.5%)	2
Neck pain	2/19 (10.5%)	2
Muscle spasms	1/19 (5.3%)	1
Musculoskeletal pain	1/19 (5.3%)	1
Tendonitis	1/19 (5.3%)	1
Nervous system disorders
Headache	3/19 (15.8%)	5
Migraine	1/19 (5.3%)	2
Neuralgia	1/19 (5.3%)	1
Sciatica	1/19 (5.3%)	1
Psychiatric disorders
Conversion disorder	1/19 (5.3%)	1
Insomnia	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/19 (5.3%)	1
Eczema nummular	1/19 (5.3%)	1
Erythema	1/19 (5.3%)	3
Rash pruritic	1/19 (5.3%)	1
Vascular disorders
Hypertension	1/19 (5.3%)	1
Hypotension	1/19 (5.3%)	1

Limitations/Caveats

This study was prematurely stopped because 4 subjects relapsed among 14 enrolled and treated subjects at the time of the early assessment of study results. LFB BIOTECHNOLOGIES judged that it was not acceptable to continue the study.

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.