Clinical trial NCT03058224: Efficacy and Safety of IGN-ES001 in Chronic Widespread Pain With or Without Fibromyalgia
Official title: Randomized, Double-blind, Placebo-controlled Exploratory Trial to Investigate Efficacy and Safety of IGN-ES001 in Patients With Chronic Widespread Pain With or Without Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Widespread Pain
Fibromyalgia
Keywords: Pain, Symptom Severity
Immunoglobulin IgY
Fibromyalgia
Widespread Pain Index
Eggyolk
FIQ-R
SF-36v2TM
MOS-SS
FSS
PGIC
Quality of life
Lead sponsor: IgNova GmbH
Sponsor class: INDUSTRY
Collaborators: name: Scope International AG
name: Klinar CRO
name: CenTrial GmbH
name: Pharmasolutions4U
name: idv Data Analysis and Study Planning
First posted: 2017-02-20
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled exploratory trial to investigate efficacy and safety of food supplement IGN-ES001 in patients with chronic widespread pain (CWP) with or without fibromyalgia (FM).

Detailed description: Patients will perform five scheduled on-site visits and five phone calls:

* Screening visit, V1 (Day -10 to -7), informed consent
* Baseline visit, V2 (Day 1), randomization, treatment start
* Phone call, V3 (Day 4 ± 1)
* Phone call, V4 (Day 8 ± 3)
* Phone call, V5 (Day 15 ± 3)
* On-site visit, V6 (Day 22 ± 3)
* Phone call, V7 (Day 29 ± 3)
* Phone call, V8 (Day 36 ± 3)
* On-site visit, V9 (Day 43 + 3), treatment end
* Follow-up on-site visit, V10 (Day 50 + 7, or 7 + 7 days after EDV).

In addition, patients may be asked to return to the trial site between scheduled visits for assessment of safety data (unscheduled visits).

The maximum duration of treatment for the individual patient will be 46 days (including allowed visit window deviation). The maximum duration of trial participation for the individual patient will be 67 days.

Eligibility criteria: Inclusion Criteria:

1. Male or female out-patient ≥ 18 years and ≤ 70 years of age.
2. Patient willing and able (e.g. mental and physical condition) to participate in all aspects of the trial, including use of investigational product, subjective completion of diaries and questionnaires, attending scheduled visits, completing telephone interviews, and compliant with protocol requirements as evidenced by providing signed writteninformed consent.
3. History of chronic widespread pain (for at least three months prior to visit V1 (screening)).
4. a.) For FM patients: Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) ≥ 5 or WPI 3-6 and SS ≥ 9 (original preliminary fibromyalgia criteria of the American College of Rheumatology (ACR) 2010).

   b.) For non-FM CWP patients: WPI ≥ 3-6 and SS ≥ 5-8 (modified from the preliminary fibromyalgia criteria of the ACR 2010).
5. Use of prior and concomitant medications/ therapies (if not excluded, see exclusion criteria no 6 and no 7), non-pharmacological therapies and lifestyle habits (e.g. diet changes, Ramadan participation, etc.) that could influence the efficacy assessments must have been stable for at least 30 days prior to visit V1 (screening) and are anticipated to be at a stable regimen throughout the trial until visit V9.
6. Patient has negative urine test at screening visit V1 for the following drugs of abuse:

   1. Amphetamine
   2. Cocaine
   3. Metamphetamine
   4. Morphine
   5. Tetrahydrocannabinol
7. Female patient is surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or at least two years postmenopausal or, if of childbearing potential, she is sexually abstinent or agrees to practice adequate contraceptive measures (hormonal contraceptives, intrauterine device, double-barrier method).
8. Patient must have completed at least 6 screening phase diary pages satisfactorily within the past 7 days before visit V2.
9. Median pain NRS must be ≥ 4 in at least 1 out of the 6 pain qualities and ≥ 4 in overall pain assessment. The median will be calculated from the last 7 days before visit V2 (baseline) and will serve as baseline value.

If all inclusion criteria are fulfilled (and none of the exclusion criteria below), the patient will be randomized at visit V2 and continues in the trial. Otherwise the patient will be excluded from trial participation.

Exclusion Criteria:

1. Patients without a basic and stable CWP therapy which started at least 30 days before V1 (screening) i.e. treatment-naive patients, first diagnosis.
2. Known allergy or intolerance to egg or egg constituents.
3. History of or currently active malignancy except for malignancies that were successfully treated and have had no recurrence within 5 years before screening visit V1.
4. Known, uncontrolled endocrine disorders, such as hypothyroidism (TSH and free T4), and diabetes mellitus (HbA1c).
5. Known severe hepatic, renal, respiratory, hematologic, neurologic, infectious, or immunologic disease, unstable cardiovascular disease, or any other medical or psychiatric condition that, in the judgment of the investigator, would make the patient inappropriate for participation in this trial.
6. Immune response modulating medication/ therapy e.g. systemic corticosteroids, antibodies other than IP (investigational product) from a period starting 90 days before visit V1 (screening).
7. WHO step-II and step-III opioids (except occasional use of codeine as cough medication) from a period starting 60 days before visit V1 (screening).
8. Intractable vomiting likely to significantly influence gastrointestinal (GI) investigational product presence.
9. Surgery within 60 days before visit V1 (screening) or anticipated or scheduled for the next nine weeks after visit V1 (screening).
10. Vaccination from a period starting 30 days prior to visit V1 (screening).
11. Known liver disease or evidence of impaired hepatic function (total bilirubin, aspartate aminotransferase \[ASAT\], alanine transaminase \[ALAT\], gamma-glutamyltransferase \[GGT\], or alkaline phosphatase \[AP\] \> 3 times the upper limit of normal).
12. Known kidney disease or evidence of impaired renal function, i.e. estimated glomerular filtration rate (eGFR) based on serum creatinine \< 60 mL/min as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
13. Pregnancy or breastfeeding.
14. Known severe psychiatric illness (e.g. schizophrenia, major depression, anxiety disorder, obsessive compulsive disorder, panic disorder, social phobia, post-traumatic stress) or personality disorder (e.g. borderline personality). Obvious suicide risk.
15. Current and/ or history of known or suspected drug or substance abuse including alcohol abuse within five years before visit V1 (screening) as stated by the patient and/ or withdrawal symptoms.
16. Previous enrolment in this trial, or participation in any other studies involving investigational products, simultaneously or within six months prior to be screened for this trial (visit V1).
17. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.
18. Employee of the investigator or trial site, with direct involvement in the proposed trial or other studies under the direction of that investigator or trial site, as well as family members of the employees or the investigators.
19. Patients unable or unwilling to include yoghurt or ayran into their daily diet.
20. Severe diarrhea.

Primary outcomes:
measure: Pain, final percent changes from baseline (based on diary), univariate analysis
timeFrame: Six Weeks
measure: Pain, final percent changes from baseline (based on diary), multivariate analysis
timeFrame: Six Weeks
measure: Pain, final responder (based on diary)
timeFrame: Six Weeks
Secondary outcomes:
measure: Responder* rate, alternative definition (based on diary)
timeFrame: Six Weeks
measure: Change in Fibromyalgia Impact Questionnaire Revised version (FIQ-R) score from baseline (visit V2)
timeFrame: Six Weeks
measure: Change in Short-Form-36 version 2 Quality-of-Life questionnaire (SF-36v2TM) score from baseline (visit V2)
timeFrame: Six Weeks
measure: Change in Medical Outcomes Study Sleep Scale (MOS-SS) score from baseline (visit V2)
timeFrame: Six Weeks
measure: Change in Fatigue Severity Scale (FSS) score from baseline (visit V2)
timeFrame: Six Weeks
measure: Patient's Global Impression of Change (PCIG) Questionnaire
timeFrame: Six Weeks
measure: Consumption of rescue medication
timeFrame: Six Weeks
measure: Time to first rescue medication (days)
timeFrame: Dependent to the timeframe of the first rescue medication from first investigational product intake following baseline visit 2 through study completion, an average of six weeks
Other outcomes:
Locations:
city: Adana
country: Turkey
facility: Çukurova University School of Medicine
city: Antalya
country: Turkey
facility: Akdeniz University School of Medicine
city: Aydın
country: Turkey
facility: Adnan Menderes University School of Medicine
city: Bursa
country: Turkey
facility: Uludağ University School of Medicine
city: Edirne
country: Turkey
facility: Trakya University School of Medicine
city: Gaziantep
country: Turkey
facility: Gaziantep University School of Medicine
city: Istanbul
country: Turkey
facility: Bezmialem Vakıf University School of Medicine
city: Istanbul
country: Turkey
facility: İstanbul Physical Treatment and Rehabilitation Training and Research Hospital
city: Istanbul
country: Turkey
facility: İstanbul University Cerrahpaşa School of Medicine
city: Istanbul
country: Turkey
facility: İstanbul University İstanbul School of Medicine
city: Istanbul
country: Turkey
facility: Maltepe University School of Medicine
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Istanbul
country: Turkey
facility: Şişli Florence Nighingale Hospital
city: Istanbul
country: Turkey
facility: Şişli Hamidiye Etfal Training and Research Hospital
city: Izmir
country: Turkey
facility: İzmir Medical Park Hospital
city: Kayseri
country: Turkey
facility: Erciyes UNiversity School of Medicine
city: Konya
country: Turkey
facility: Necmettin Erbakan University School of Medicine
city: Sakarya
country: Turkey
facility: Sakarya University School Of Medicine Korucuk Training and Research Hospital
city: Sivas
country: Turkey
facility: Cumhuriyet University School of Medicine
city: Tekirdag
country: Turkey
facility: Namık Kemal University School of Medicine
city: Trabzon
country: Turkey
facility: Karadeniz Technical University School of Medicine
city: Zonguldak
country: Turkey
facility: Bülent Ecevit University School of Medicine
city: Çanakkale
country: Turkey
facility: Onsekiz Mart University School of Medicine
Study officials:
References: