A Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions

Sponsor

IMMUNOe Research Centers (Industry)

Overall Status

Completed

CT.gov ID

NCT03576469

Collaborator

(none)

Enrollment

Location

Arm

20.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients receiving intravenous immunoglobulin (IVIG) therapy for primary immunodeficiency and neurologic conditions may experience adverse drug reactions (ADRs). The mechanism of the ADR is unknown. Currently, the standard practice for these patients is to change from IV to subcutaneous IG (SCIG) but because of the need of immunomodulation or patient preference, SCIG may not be an option. Data has shown that some levels of complement decrease from pre- to post-infusion of IVIG. This study is to determine if replacing this complement protein may ameliorate ADRs.

Condition or Disease	Intervention/Treatment	Phase
CVI - Common Variable Immunodeficiency	Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)	Phase 4

Detailed Description

This is a single-site, pilot study conducted in the US to determine the benefit of human C1-esterase inhibitor [recombinant] (C1-INH-R) therapy to ameliorate ADRs in subjects receiving IVIG therapy experience ADRs post-infusion. Subjects who are currently receiving IVIG for immunodeficiency or neurologic conditions and experience ADRs will be enrolled.

In part 1, subjects will continue to receive IVIG for two infusions. Complement proteins will be measured pre- and post-infusion. Quality of life and other questionnaires will be administered.

In part 2, subjects will receive C1-INH-R infusion prior to receiving IVIG infusion for three infusions. Complement proteins will be measured pre- and post- infusion. Quality of life and other questionnaires will be administered.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single GroupSingle Group

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions

Actual Study Start Date :

Jun 13, 2018

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: C1-esterase inhibitor [recombinant] (C1-INH-R) Single-site, open-label arm to evaluate the benefit of C1-INH-R in subjects on IVIG therapy who experience ADRs. The study will have 2 periods: 6 - 8 weeks - subjects will receive 2 infusions of IVIG 9 - 12 weeks - subjects will receive 3 infusions of C1-INH-R prior to IVIG infusion	Biological: C1-esterase inhibitor [recombinant] (C1-INH-R) C1-INH-R is FDA approved and indicated for the treatment of acute attacks of angioedema in adolescent and adult patients with Hereditary Angioedema (HAE) as a replacement for low levels of C1-esterase inhibitor or low function of C1-esterase inhibitor

Arm

Intervention/Treatment

Experimental: C1-esterase inhibitor [recombinant] (C1-INH-R)

Single-site, open-label arm to evaluate the benefit of C1-INH-R in subjects on IVIG therapy who experience ADRs. The study will have 2 periods: 6 - 8 weeks - subjects will receive 2 infusions of IVIG 9 - 12 weeks - subjects will receive 3 infusions of C1-INH-R prior to IVIG infusion

Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)

C1-INH-R is FDA approved and indicated for the treatment of acute attacks of angioedema in adolescent and adult patients with Hereditary Angioedema (HAE) as a replacement for low levels of C1-esterase inhibitor or low function of C1-esterase inhibitor

Outcome Measures

Primary Outcome Measures

The change in Modified Fatigue Severity Scale (mFSS) [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated Rasch-built 7-item modified fatigue survey scale. Scale rated 0 - 3 (3 = agree, 0 = less agree)
The change in Modified Fatigue Impact Scale (MFIS) [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated 24 item questionnaire measuring the impact of fatigue rated 0 - 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always)
The change in Migraine Disability Assessment (MIDAS) [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Headache severity measurement of number of days affected after infusion
The change in Headache Impact Scale (HIT-6) [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated measurement of the impact headaches have on the ability to function on the job, at school, at home and in social situations. 6 item questionnaire rated from never (6 points each), rarely (8 points each), sometimes (10 points each), very often (11 points each), always (13 points each). The higher number the more the impact.
The change in Activities of Daily Living Sliding Scale [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated 10 point scale measuring level of activity with 1 being the worst (least) and 10 being the best (greatest)
The change in Activities of Daily Living Questionnaire [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Calculates the number of days missed from work, school/daycare/activities, housework, and regular exercise
The change in Energy Sliding Scale [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated10 point scale measuring energy level with 1 being the worst (Lowest) and 10 being the best (highest)
The change in Infection Questionnaire [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated 7 item infection questionnaire measured from 1 to 10 with 1 being the least affected and 10 being the most affected.
The change in Perceived Deficits Questionnaire - cognitive assessment [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Subject-rated 20 item questionnaire measuring memory, attention and concentration rated 0 to 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always) with the lower score being least impact.
The change in 36 item short form survey (SF-36) [Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)]
Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view.
Change in the number of ADRs [Measured at each infusion (every 3 - 4 weeks)]
Adverse reactions to infusions

Secondary Outcome Measures

Change in levels of C1-INH pre- and post-infusion [Measurement at each infusion (every 3 - 4 weeks)]
Laboratory levels of C1-INH total and functional

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years and older experiencing ADRs related to IVIG infusions
Stable dose of IVIG for 3 months
Willing to comply with all aspects of the protocol, including blood draws
Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. Acceptable forms of contraception are defined as those with a failure rate < 1% when properly applied and include: a combination oral pill, some intra-uterine devices, and a sterilized partner in a stable relationship. Female patients must not be pregnant, planning to become pregnant, or be actively breastfeeding through the entire study period.

Exclusion Criteria:

Receiving treatment for HAE, either prophylactic or acute therapy
Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH)
Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant.
Patients who, in the investigator's opinion, might not be suitable for the trial