NCT04918771

Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old

Completed Phase 3 Results posted Last updated 15 October 2024

What this trial tests

Phase 3 trial testing Raphamin in Acute Respiratory Viral Infection in 435 participants. Completed in 21 July 2023.

Timeline

29 April 2021

Primary endpoint
21 July 2023

21 July 2023

Quick facts

Lead sponsor	Materia Medica Holding
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	435
Start date	29 April 2021
Primary completion	21 July 2023
Estimated completion	21 July 2023
Sites	29 locations across Russia

Drugs / interventions tested

• Raphamin — full drug profile →
• Placebo

Conditions studied

• Acute Respiratory Viral Infection — all drugs for Acute Respiratory Viral Infection →

Sponsor

Materia Medica Holding — full company profile →

Who can join

Adults 12 to 18, any sex, with Acute Respiratory Viral Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR)). Primary · 14 days of observation

Outcome Measure is evaluated on the basis of ARVI, confirmed by Polymerase chain reaction (PCR), i.e virus detection. ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To

Group	Value	95% CI
Raphamin	3.3	± 1.7
Placebo	4.4	± 2.6

Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed). Secondary · Day1 through Day6 of the treatment and observation

The outcome measure is based on the area under the curve (AUC) for the TSS (Total symptoms score). TSS is calculated as a sum of scores for 14 different symptoms. 13 of them are different ARVI manifestations, each of them is evaluated on a scale: 0 (none), 1 (mild), 2 (moderate), 3 (severe). 14th symptom is body temperature (temp) which is converted to its score using following rules: if temp \<= 37.3 then score = 0 (none) if 37.3 \< temp \<= 38.0 then score = 1 (mild) if 38.0 \< temp \<= 39.0 then score = 2 (moderate) if 39.0 \< temp then score = 3 (severe) So it is 14 symptoms and the scor

Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed), AUC score

Group	Value	95% CI
Raphamin	44.6	± 23.8
Placebo	46.9	± 24.3

Severity of ARVI (PCR-confirmed), AUC score

Group	Value	95% CI
Raphamin	48.3	± 25.2
Placebo	53.6	± 25.6

Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed). Secondary · 14 days of observation

ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the

Day 2

Group	Value	95% CI
Raphamin	24
Placebo	16

Day 3

Group	Value	95% CI
Raphamin	64
Placebo	46

Day 4

Group	Value	95% CI
Raphamin	96
Placebo	94

Day 5

Group	Value	95% CI
Raphamin	149
Placebo	136

Day 6

Group	Value	95% CI
Raphamin	174
Placebo	162

Day 7

Group	Value	95% CI
Raphamin	191
Placebo	181

Time to Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed). Secondary · 14 days of observation

ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TSS absolute axillar temperature (in degrees Celsius) was converted to relative units (or points) using the

Group	Value	95% CI
Raphamin	3.4	± 1.8
Placebo	3.9	± 2.4

Percentage of Patients With Resolution of ARVI Symptoms (PCR-confirmed). Secondary · 14 days of observation

Outcome Measure is based on the Percentage of Patients With Resolution of ARVI, confirmed by Polymerase chain reaction (PCR), i.e virus detection. ARVI's resolution criteria: temperature ≤37.3°С + total symptom score (TSS) ≤2. Axillar temperature, 6 flu-like nonspecific symptoms (headache, chills, sweating, weakness, muscle pain, drowsiness) and 7 nasal/throat/chest symptoms (runny nose, nasal congestion, sneezing, hoarseness, sore throat, cough, pain/heaviness in chest) were registered for TSS according to the 4-point scale for each of them (0 = no symptom; 1 = mild symptom; 2 = moderate sym

Day 2

Group	Value	95% CI
Raphamin	16
Placebo	4

Day 3

Group	Value	95% CI
Raphamin	36
Placebo	16

Day 4

Group	Value	95% CI
Raphamin	59
Placebo	39

Day 5

Group	Value	95% CI
Raphamin	95
Placebo	64

Day 6

Group	Value	95% CI
Raphamin	107
Placebo	77

Day 7

Group	Value	95% CI
Raphamin	119
Placebo	89

Dosing Frequency of Antipyretics. Secondary · 3 days of therapy

Outcome Measure is based on the rates of antipyretic use per patient during days 1 to 3 of therapy according to the electronic patient diary.

Day 1

Group	Value	95% CI
Raphamin	0.43	± 0.72
Placebo	0.39	± 0.72

Day 2

Group	Value	95% CI
Raphamin	0.22	± 0.61
Placebo	0.25	± 0.66

Day 3

Group	Value	95% CI
Raphamin	0.09	± 0.38
Placebo	0.07	± 0.31

Percentage of Patients Reporting Worsening of Illness. Secondary · Day 4 through day 14 of the treatment and observation period

Outcome Measure is based on the rates of Complications that require the use of antibiotics or hospitalization.

Group	Value	95% CI
Raphamin	1
Placebo	0

Occurrence and Type of Adverse Events (AE) During the Treatment. AE Severity. Secondary · 14 days of observation

1. The intensity (severity) of adverse events. 2. Causal relationship of AEs to the sudy drug. 3. Outcome of AEs. Based on medical records.

Severity/Mild

Group	Value	95% CI
Raphamin	2
Placebo	6

Severity/Moderate

Group	Value	95% CI
Raphamin	5
Placebo	0

Causal relationship/Not connected

Group	Value	95% CI
Raphamin	7
Placebo	6

Outcome/Recovery

Group	Value	95% CI
Raphamin	6
Placebo	5

Outcome/Unknown

Group	Value	95% CI
Raphamin	1
Placebo	1

Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm). Secondary · Day 1 through day 7 of the treatment and observation period.

The outcome measure is based on the medical records. The patient's heart rate (heart rate) is measured by the physician in every visit (on days 1, 5, and 7).

Visit 1

Group	Value	95% CI
Raphamin	87.1	± 11.4
Placebo	87.2	± 10.6

Visit 2

Group	Value	95% CI
Raphamin	77.9	± 7.1
Placebo	78.1	± 7.2

Visit 3

Group	Value	95% CI
Raphamin	76.3	± 7.0
Placebo	76.7	± 6.8

Changes in Vital Signs: Respiration Rate/Breathing Rate in Breaths Per Minute. Secondary · Day 1 through day 7 of the treatment and observation period.

Outcome Measure is based on the medical records. The patient's respiration rate (breathing rate) is measured by physician in every visit (on days 1, 5, and 7).

Visit 1

Group	Value	95% CI
Raphamin	20.8	± 3.3
Placebo	20.7	± 2.8

Visit 2

Group	Value	95% CI
Raphamin	18.4	± 1.9
Placebo	18.6	± 1.7

Visit 3

Group	Value	95% CI
Raphamin	18.0	± 1.7
Placebo	18.2	± 1.7

Changes in Vital Signs: Blood Pressure in Units of Millimeters of Mercury (mmHg). Secondary · Day 1 through day 7 of the treatment and observation period.

Outcome Measure is based on the medical records. The patient's blood pressure is measured by the physician in every visit (on days 1, 5, and 7).

Visit 1/Systolic blood pressure

Group	Value	95% CI
Raphamin	112	± 9.9
Placebo	112	± 8.9

Visit 2/Systolic blood pressure

Group	Value	95% CI
Raphamin	111	± 9.8
Placebo	112	± 8.7

Visit 3/Systolic blood pressure

Group	Value	95% CI
Raphamin	111	± 10.2
Placebo	111	± 9.4

Visit 1/Diastolic blood pressure

Group	Value	95% CI
Raphamin	70.0	± 5.7
Placebo	69.8	± 5.8

Visit 2/Diastolic blood pressure

Group	Value	95% CI
Raphamin	69.7	± 5.7
Placebo	69.5	± 5.4

Visit 3/Diastolic blood pressure

Group	Value	95% CI
Raphamin	69.6	± 5.7
Placebo	69.4	± 5.9

Percentage of Patients With Clinically Relevant Abnormal Laboratory Findings. Secondary · Day 1 through day 7 of the treatment and observation period.

Outcome Measure is based on the Hematology, blood chemistry, and urinalysis parameters, which are beyond the reference values at the end of treatment.

Group	Value	95% CI
Raphamin	1
Placebo	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Registration of AEs begins after the first dose of study drug and continues throughout the entire period of study therapy - 14 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Raphamin

Serious: 1/206 (0%)

Deaths: 0/206

Placebo

Serious: 0/214 (0%)

Deaths: 0/214

Serious adverse events (1 terms)

Reaction	System	Raphamin	Placebo
Worsening flu	Infections and infestations	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Raphamin	Placebo
Adenoiditis	Infections and infestations	—	—
Bacterial superinfection	Infections and infestations	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Coronavirus infection COVID-19	Infections and infestations	—	—
Increased percentage of monocytes	Investigations	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—
Dizziness	Nervous system disorders	—	—
Loss of consciousness	Nervous system disorders	—	—
Pallor	Vascular disorders	—	—
Flu	Infections and infestations	—	—

Most-reported serious reactions: Worsening flu.

Data from ClinicalTrials.gov NCT04918771 adverse events section.

Sponsor's own description

The multicenter double-blind placebo-controlled randomized in parallel-group. The objective of this study is to evaluate efficacy and safety of Raphamin in the treatment of acute respiratory viral infection (ARVI) in children aged 12-18 years old.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.