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FAST Fish Phase IIb Clinical Trial for the Treatment of Fish Allergy by Subcutaneous Immunotherapy (FASTIIb)

Primary Purpose

Food Allergy to Fish

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

FAST fish mCyp c 1

Placebo

About this trial

This is an interventional treatment trial for Food Allergy to Fish focused on measuring fish allergy, parvalbumin, immunotherapy, mCyp c 1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subject having given a written informed consent before completing any study related procedure.
Male or female subject from 18 to 65 years old and in general good health as determined by past medical history and physical examination.
For woman of child bearing potential:
- a negative urine pregnancy test at screening visit,
- the subject must receive/ use a medically effective contraceptive method during the study.
Convincing case history of allergy (immediate allergic reaction ≤ 2 hours) to fish ingestion.
Specific IgE to fish by both a positive (3mm mean wheal diameter over negative control) SPT to cod extract and an ImmunoCAP ≥ class 2 (0.70 kUA/L) for cod (f3) and rCyp c 1 at screening.
Positive DBPCFC with cod at screening visits.
FEV1 ≥ 80% of predicted values at screening.
Subject accepting to comply fully with the protocol.

Exclusion Criteria:

Placebo-reaction in DBPCFC.
Food anaphylaxis: anaphylactic shock (a score of 2 or 3 on cardiovascular/ neurologic symptoms according to PRACTALL (1): score 2 = drop in blood pressure and/or >20% from baseline, or significant change in mental status- score 3 = cardiovascular collapse, signs of impaired circulation/ unconscious) due to fish intake, both during the past and at screening DBPCFC.
Ongoing immunotherapy (IT) with any kind of allergen.
Ongoing or previous treatment with omalizumab.
Any clinical condition that contraindicates IT (EAACI guidelines) (8): serious immunological diseases, major cardiovascular disease, cancer, chronic infections, lack of compliance and severe psychological disorders.
Any significant clinical condition that the investigators judged might hamper the patient's safety or the study outcomes. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, mental disease, immunological and endocrine disease.
Chronic urticaria.
Severe atopic dermatitis or non-controlled atopic dermatitis.
Ongoing treatment with betablockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor II antagonists (ARA II).
Pregnancy or nursing.
Uncontrolled asthma (asthma, if present, should be well controlled according to GINA guidelines using any kind of drugs except oral corticosteroids and omalizumab).
An FEV1<80% of predicted value during screening spirometry.
Subject who has participated in a clinical trial within 3 months prior to this one.
Subject with a history of drug or alcohol abuse.
Investigators, co-investigators, as well as their children or spouses and all the study collaborators should not be enrolled in the study.
Patients with concurrent allergy symptoms can be included if patients can manage without antihistamines and/or leukotriene receptor antagonists five days prior each screening and treatment visit.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FAST fish mCyp c 1

Placebo

Arm Description

Subcutaneous injections of investigational medicinal product mCyp c 1 formulated in a solution (suspension) with aluminium. Up-dosing (build-up) phase: each subject will receive 10 injections of active or placebo treatment. The first three injections will be given on the first day. For those on active treatment the dosing will begin at 6ng and conclude on week 8 with the administration of 60μg. Maintenance phase: the maintenance dose of 60μg will be repeated once at two weeks and then monthly for a period of four months (four monthly injections).

Subcutaneous injections of exactly the same dosage, frequency and duration as Active Arm but all injections will be performed with placebo (has the same composition as the active drug suspension but no allergen mCyp c 1 is added).

Outcomes

Primary Outcome Measures

Efficacy of subcutaneous immunotherapy with mCyp c 1 for the treatment of fish allergy (change from baseline in the threshold of fish protein that induces an allergic reaction)

The primary outcome measure will be efficacy as determined by the change from baseline in the threshold of fish protein that induces an allergic reaction. This threshold will be assessed by means of a standardized double blind placebo controlled food challenge (DBPCFC) with cod-fish after completion of six months of immunotherapy. Success is defined as a statistically significant change in the threshold dose of protein that provokes a reaction in DBPCFC.

Secondary Outcome Measures

Safety (recording of adverse events)- Number of participants with adverse events and recording of the nature of adverse events

The fundamental secondary endpoint will be safety as indicated by clinical safety and tolerability and by the careful recording of adverse events; other surrogates of safety will be: physical examination, vital signs, 12-Lead ECG and laboratory evaluations.

Severity of reaction in food challenge

To study any possible change from baseline in the severity of the reaction in the baseline Double Blind Placebo Controled Food Challenge (DBPCFC) after treatment with mCyp c 1

Skin prick test (SPT) reactivity

To study any possible change(s) from baseline in skin prick test (SPT) reactivity against fish and mCyp c 1 (titrated) after treatment with mCyp c 1

Serum specific IgE, IgG, IgG4 and IgA antibodies

To study any possible change(s) from baseline in serum specific IgE, IgG, IgG4 and IgA antibodies against fish and rCyp c 1 (ImmunoCAP) after treatment with mCyp c 1

Biological activity of IgE

To study any possible change from baseline in the biological activity of IgE (stripped basophil histamine release test) after treatment with mCyp c 1

Full Information

NCT ID

NCT02382718

First Posted

February 18, 2015

Last Updated

June 9, 2017

Sponsor

George Stavroulakis

Collaborators

Hospital San Carlos, Madrid, Odense University Hospital, Medical University of Lodz, National and Kapodistrian University of Athens, Landspitali University Hospital, National University Hospital NUHD Denmark, Universitiy Medical Centre Utrecht UMCU The Netherlands, Hospital Universitario Reina Sofia (Cordoba) Spain, Hospital Regional de Malaga

1. Study Identification

Unique Protocol Identification Number

NCT02382718

Brief Title

FAST Fish Phase IIb Clinical Trial for the Treatment of Fish Allergy by Subcutaneous Immunotherapy

Acronym

FASTIIb

Official Title

A Multinational Phase IIb Study to Investigate the Efficacy and Safety of Subcutaneous Immunotherapy With a Modified Fish- Parvalbumin Given in Single Rising and Maintenance Doses to Subjects Allergic to Fish

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

October 2015 (undefined)

Primary Completion Date

February 2017 (Actual)

Study Completion Date

April 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

George Stavroulakis

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a phase IIb clinical trial to investigate the efficacy and safety of subcutaneous immunotherapy with a modified parvalbumin called mCyp c 1 for the treatment of fish allergy to subjects allergic to fish.

Detailed Description

Fish allergy is a persistent food allergy (usually lifelong) which can be life threatening due to the danger for anaphylaxis (severe allergic reaction) upon accidental exposure to fish. Until today there is no curative treatment for fish allergy. The only treatment is avoidance. Patients with fish allergy have to avoid fish of all types and carry an adrenaline autoinjector and rescue medication, in case of accidental exposure to fish. That way patients with fish allergy have to continuously control what they are eating and this causes a great deal of stress and impacts their quality of life. The major allergen responsible for fish allergy is the protein parvalbumin. It is recognized by the vast majority (96-100%) of fish allergic patients. During the past, treatment of food allergy with immunotherapy was successful but dangerous, due to serious side effects (anaphylaxis). A novel biotechnological product, a recombinant hypoallergenic parvalbumin, called mCyp c 1, is used for the first time in a phase IIb clinical trial, to test the efficacy of subcutaneous immunotherapy for the treatment of fish allergy. The investigational medicinal product mCyp c1, is based on the recombinant wild type carp parvalbumin (rCyp c 1) and is the result of site directed mutagenesis, by which the disruption of the two calcium binding sites of carp parvalbumin is performed. The modified parvalbumin mCyp c 1, is both hypoallergenic and immunogenic. That way it is a promising molecule for the safe and effective treatment of fish allergy. This molecule has proven to be safe in a phase I/IIa study that has been performed, during which mCyp c 1 was administered with subcutaneous injections. During this study only local reactions at the injection site were observed. There were no observed systemic reactions. Even more, there were clear indications that mCyp c 1 was recognized by the immune system. The results of this phase I/IIa study guarantee the necessity of a phase IIb clinical trial with mCyp c 1, in order to study the efficacy of this modified parvalbumin in the treatment of fish allergy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Food Allergy to Fish

Keywords

fish allergy, parvalbumin, immunotherapy, mCyp c 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FAST fish mCyp c 1

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

FAST fish mCyp c 1

Other Intervention Name(s)

mCyp c 1

Intervention Description

Subcutaneous immunotherapy

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Subcutaneous immunotherapy

Primary Outcome Measure Information:

Title

Efficacy of subcutaneous immunotherapy with mCyp c 1 for the treatment of fish allergy (change from baseline in the threshold of fish protein that induces an allergic reaction)

Description

Time Frame

7 months after treatment begining

Secondary Outcome Measure Information:

Title

Safety (recording of adverse events)- Number of participants with adverse events and recording of the nature of adverse events

Description

Time Frame

Up to 13 months

Title

Severity of reaction in food challenge

Description

To study any possible change from baseline in the severity of the reaction in the baseline Double Blind Placebo Controled Food Challenge (DBPCFC) after treatment with mCyp c 1

Time Frame

7 months after treatment begining

Title

Skin prick test (SPT) reactivity

Description

To study any possible change(s) from baseline in skin prick test (SPT) reactivity against fish and mCyp c 1 (titrated) after treatment with mCyp c 1

Time Frame

7 months after treatment begining

Title

Serum specific IgE, IgG, IgG4 and IgA antibodies

Description

To study any possible change(s) from baseline in serum specific IgE, IgG, IgG4 and IgA antibodies against fish and rCyp c 1 (ImmunoCAP) after treatment with mCyp c 1

Time Frame

7 months after treatment begining

Title

Biological activity of IgE

Description

To study any possible change from baseline in the biological activity of IgE (stripped basophil histamine release test) after treatment with mCyp c 1

Time Frame

7 months after treatment begining

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject having given a written informed consent before completing any study related procedure. Male or female subject from 18 to 65 years old and in general good health as determined by past medical history and physical examination. For woman of child bearing potential: a negative urine pregnancy test at screening visit, the subject must receive/ use a medically effective contraceptive method during the study. Convincing case history of allergy (immediate allergic reaction ≤ 2 hours) to fish ingestion. Specific IgE to fish by both a positive (3mm mean wheal diameter over negative control) SPT to cod extract and an ImmunoCAP ≥ class 2 (0.70 kUA/L) for cod (f3) and rCyp c 1 at screening. Positive DBPCFC with cod at screening visits. FEV1 ≥ 80% of predicted values at screening. Subject accepting to comply fully with the protocol. Exclusion Criteria: Placebo-reaction in DBPCFC. Food anaphylaxis: anaphylactic shock (a score of 2 or 3 on cardiovascular/ neurologic symptoms according to PRACTALL (1): score 2 = drop in blood pressure and/or >20% from baseline, or significant change in mental status- score 3 = cardiovascular collapse, signs of impaired circulation/ unconscious) due to fish intake, both during the past and at screening DBPCFC. Ongoing immunotherapy (IT) with any kind of allergen. Ongoing or previous treatment with omalizumab. Any clinical condition that contraindicates IT (EAACI guidelines) (8): serious immunological diseases, major cardiovascular disease, cancer, chronic infections, lack of compliance and severe psychological disorders. Any significant clinical condition that the investigators judged might hamper the patient's safety or the study outcomes. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, mental disease, immunological and endocrine disease. Chronic urticaria. Severe atopic dermatitis or non-controlled atopic dermatitis. Ongoing treatment with betablockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor II antagonists (ARA II). Pregnancy or nursing. Uncontrolled asthma (asthma, if present, should be well controlled according to GINA guidelines using any kind of drugs except oral corticosteroids and omalizumab). An FEV1<80% of predicted value during screening spirometry. Subject who has participated in a clinical trial within 3 months prior to this one. Subject with a history of drug or alcohol abuse. Investigators, co-investigators, as well as their children or spouses and all the study collaborators should not be enrolled in the study. Patients with concurrent allergy symptoms can be included if patients can manage without antihistamines and/or leukotriene receptor antagonists five days prior each screening and treatment visit.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ronald van Ree, Professor

Organizational Affiliation

FAST Consortium under EU 7th FP

Official's Role

Study Chair

Facility Information:

Facility Name

National University Hospital NUHD Denmark

City

Gentofte

ZIP/Postal Code

DK-2900

Country

Denmark

Facility Name

Odense University Hospital OUH Denmark

City

Odense

ZIP/Postal Code

DK 5000

Country

Denmark

Facility Name

Sotiria General Hospital for the Diseases of the Thorax

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Landspitali University Hospital Reykjavik LSH Iceland

City

Reykjavik

ZIP/Postal Code

101

Country

Iceland

Facility Name

Universitiy Medical Centre Utrecht UMCU The Netherlands

City

Utrecht

ZIP/Postal Code

85500

Country

Netherlands

Facility Name

Medical Universtity of Lodz

City

Lodz

Country

Poland

Facility Name

Hospital Universitario Reina Sofia (Cordoba) Spain

City

Cordoba

ZIP/Postal Code

14004

Country

Spain

Facility Name

Hospital Clinico San Carlos SERMAS Spain

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Hospital Regional Universitario de Malaga Spain

City

Malaga

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://www.allergome.org/fast/index.jsp

Description

FAST Consortium and FAST study website

Learn more about this trial

FAST Fish Phase IIb Clinical Trial for the Treatment of Fish Allergy by Subcutaneous Immunotherapy

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FAST Fish Phase IIb Clinical Trial for the Treatment of Fish Allergy by Subcutaneous Immunotherapy (FASTIIb)

Food Allergy to Fish

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial