Clinical trial NCT01651715: Efficacy and Safety Study of Homeopathic Oral Antibodies to Treat Viral Upper Respiratory Tract Infections
Official title: Multicentre, Randomised, Double-blind, Parallel, Placebo-controlled Study Evaluating the Efficacy and Safety of Early Self-Treatment of Viral Upper Respiratory Tract Infections With Homeopathic Oral Antibodies to the TLR3 FYW Peptide (TAO1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Common Cold
Lead sponsor: Theranor s.p.r.l
Sponsor class: INDUSTRY
First posted: 2012-07-27
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether early self-treatment with homeopathic dilutions of oral antibodies to a key-protein of the immune system are effective and safe in the treatment of viral upper respiratory tract infections

Detailed description: TAO1 is an investigational medicinal product containing homoeopathic dilutions (\<10-24M) of antibodies purified from the serum of rabbit immunised against a synthetic peptide with an amino acid sequence selected in the human toll-like receptor type 3 sequence (anti-TLR3). It is intended for the treatment of viral Upper Respiratory Tract Infections (URTIs) such as common cold, influenza or influenza-like illnesses.

The validity of the TAO1 development approach was addressed in a proof of concept study of efficacy in a non-lethal influenza infection in mice. In this blinded study, TAO1 was given in drinking water for 5 days before and 10 days after viral challenge. The statistical analysis of preclinical data was carried out by using the Mann-Whitney non-parametric test (2-tailed). The clinical disease duration was significantly reduced from 6.0 (5.25 (25th percentile);7.0 (75th percentile)) days to 5.0 (5.0;5.0) days (p=0.00037) as well as the overall disease severity that was lowered from 8.0 (7.0;10.0) points to 6.0 (5.0;7.5) points (p=0.00032).

Given the high homoeopathic dilution, the active substance in the finished product lies beyond sensitivity of existing analytical assays. TAO1 is therefore not amenable to pharmacokinetics studies.

There are currently no data on clinical efficacy of TAO1 in common cold obtained in double-blind placebo-controlled clinical trials. Based on the efficacy in the animal model, the expected magnitude of effect of TAO1 in humans is a reduction of common cold duration by 2-3 days, provided that the treatment is started early after the onset of the symptoms.

Primary objective:

To evaluate the efficacy of TAO1 in reducing the severity of symptoms of common cold in otherwise healthy adults.

Secondary objectives:

To evaluate the efficacy of TAO1 in reducing the duration of common cold. To evaluate the impact of TAO1 on health-related Quality of Life (functional impairment) in patients with common cold.

To evaluate the safety of TAO1.

Experimental design: Double-blind, parallel-group, randomised, multicentre, placebo-controlled study.

Treatment allocation: Balanced allocation between TAO1 and placebo (1:1).

At Visit 1, the medications, questionnaires and diary cards will be dispensed to patients who have signed informed consent. Upon contracting a common cold, they will start the treatment immediately and take contact with the doctor by phone within 36 hours. On Day 2-3 after the onset of disease, they will visit the doctor (Visit 2) to confirm the diagnosis. The doctor will check if questionnaires are filled in correctly. On the 10-14th day (at the latest) after start of treatment, Visit 3 is planned to pick up questionnaires, evaluate safety, disease complications and treatment compliance.

Treatment group: TAO1 tablets (to be dissolved in the mouth, not to be swallowed; should be taken at least 10 minutes apart from meals and/or smoking):

Day 1: 3 tablets to be taken over the first 2 hours of treatment, then 3 tablets over the rest of Day 1,

Days 2-3: 5 tablets/day (intakes distributed evenly over the daytime),

Days 4-7: 3 tablets/day (intakes distributed evenly over the daytime).

Control: Placebo tablets: same dosage regimen as for TAO1.

Concomitant medications: Only oral analgesics/antipyretics, such as paracetamol or ibuprofen, will be allowed in case of fever or headache. Each intake of such medications will be registered in the patient's diary.

Severity and duration of self-reported symptoms evaluated daily by the validated Wisconsin Upper Respiratory Symptom Survey short version (WURSS-21)

Evaluation of safety: adverse events (AEs) and serious adverse events (SAEs) coded using the Medical Dictionary for Regulatory Activities (MedDRA) assessed according to their frequency, severity, outcome and relationship to the study drug.

Data collection: Paper Case Report Form (CRF).

Duration of treatment: 7 days

Duration of study: maximum 10 months.

Number of Investigators: about 35 investigators (General Practitioners).

Type of study: Phase II, self-contained study

Number of patients: 240 (120 treated with TAO1 and 120 treated with placebo)

Sample size justification: A sample size of 115 in each group will have 80% power to detect a difference in mean AUCs of 103 (a difference of 30% between a Placebo AUC mean of 310 and a TAO1 AUC mean of 207) assuming that the common standard deviation is 277 using a two group t-test with a 0.050 two-sided significance level.

Eligibility criteria: Inclusion Criteria:

* Outpatients aged \> or = 18 years
* Ability and willingness to adhere to the study protocol
* Signed informed consent
* Self-reported recently emerged symptoms of common cold: answer "Yes" to the question "Do you believe that you are coming down with a cold?"
* At least one of the following 4 common cold symptoms: sneezing, runny nose, nasal obstruction and/or sore throat, with no limitations of symptom severity.

Exclusion Criteria:

* Specific chronic diseases (autoimmune disease, chronic bronchitis, human immunodeficiency virus (HIV) infection, lupus, rheumatoid arthritis)
* Malignancy for which the patient has undergone resection, radiation or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.
* Cancer therapy
* Immunosuppressant therapies
* Use of systemic corticosteroids
* A history of asthma or allergic rhinitis and corresponding symptoms (itchy eyes, sneezing, wheezing)
* Any of the common cold symptoms persisting since more than 36 hours
* Use of other homeopathic drugs designed to treat URTIs
* Use of antibiotics, anti-histaminergic drugs or decongestants
* Participation in another clinical trial within one month prior to treatment start
* Previous participation (receipt of randomised treatment) in this study

Primary outcomes:
measure: Severity of symptoms of common cold
timeFrame: Since start of symptoms of common cold up to the visit 3 (day 10-14)
Secondary outcomes:
measure: Duration of common cold
timeFrame: Since start of symptoms of common cold up to visit 3 (Day 10-14)
measure: Functional impairments in the course of the disease
timeFrame: Since start of symptoms of common cold up to visit 3 (Day 10-14)
measure: The need of symptomatic analgesics/antipyretics
timeFrame: Since start of symptoms of common cold up to visit 3 (Day 10-14)
measure: Evaluation of safety
timeFrame: since start of symptoms of common cold up to visit 3 (Day 10-14)
Other outcomes:
Locations:
city: Deurne
country: Belgium
facility: Frank Heyvaert
state: Antwerpen
city: Geel
country: Belgium
facility: Christel Van Der Geer
state: Antwerpen
city: Geel
country: Belgium
facility: Hugo Loos
state: Antwerpen
city: Mol
country: Belgium
facility: Jan Joris
state: Antwerpen
city: Vorst
country: Belgium
facility: Jan De Jongh
state: Antwerpen
city: Baisy-Thy
country: Belgium
facility: Jean-Pierre Devaux
state: Brabant
city: Bruxelles
country: Belgium
facility: Virginie Risse
state: Brabant
city: Kraainem
country: Belgium
facility: Roel De Ryck
state: Brabant
city: Linkebeek
country: Belgium
facility: ResearchLink sprl
state: Brabant
city: Melsbroek
country: Belgium
facility: Stéphane Vanden Bemden
state: Brabant
city: Steenokkerzeel
country: Belgium
facility: Bart Van Essche
state: Brabant
city: Tremelo
country: Belgium
facility: Erik Schreurs
state: Brabant
city: Tremelo
country: Belgium
facility: Lode Vermeersch
state: Brabant
city: Vilvoorde
country: Belgium
facility: Luc De Munck
state: Brabant
city: Braine-le-Comte
country: Belgium
facility: Patrice Lechien
state: Hainaut
city: Ecaussinnes
country: Belgium
facility: Charles Corbisier
state: Hainaut
city: Gozée
country: Belgium
facility: Elise De Meulemeester
state: Hainaut
city: Gozée
country: Belgium
facility: Magali Trefois
state: Hainaut
city: Ham-sur-Heure Nalinnes
country: Belgium
facility: Aubry Robert
state: Hainaut
city: Ham-sur-Heure Nalinnes
country: Belgium
facility: Philippe Jacques
state: Hainaut
city: Pont-à-Celles
country: Belgium
facility: Michel Grégoire
state: Hainaut
city: Thuin
country: Belgium
facility: Etienne Demanet
state: Hainaut
city: Thuin
country: Belgium
facility: Maria Buscemi
state: Hainaut
city: Beringen
country: Belgium
facility: Etienne Plees
state: Limburg
city: Ham
country: Belgium
facility: Nicole Olaerts
state: Limburg
city: Leopoldsburg
country: Belgium
facility: Paul Beke
state: Limburg
city: Overpelt
country: Belgium
facility: Steven Windmolders
state: Limburg
city: Paal
country: Belgium
facility: Jan Behets
state: Limburg
city: Paal
country: Belgium
facility: Jos Weckx
state: Limburg
city: Tessenderlo
country: Belgium
facility: Herman Van Den Broeck
state: Limburg
city: Gribomont
country: Belgium
facility: Yvan Calozet
state: Luxembourg
city: Libramont-Chevigny
country: Belgium
facility: Pierre-Henri Arnould
state: Luxembourg
city: Heusden
country: Belgium
facility: Guy Van Damme
state: Oost Vlaanderen
Study officials:
affiliation: RESEARCHLINK sprl
name: Stéphane Heijmans, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ECSOR sa/nv
name: Luc Moriau, PhD
role: STUDY_DIRECTOR
affiliation: THERANOR sprl
name: Michel Thiry, PhD
role: STUDY_CHAIR
References: