Exploratory Ph I Trial of the Active IMP in Healthy Volunteers in Relation to COVID-19

• ClinicalTrials.gov Identifier: NCT04632706
• Recruitment Status: Completed
• First Posted: November 17, 2020
• Results First Posted: December 27, 2021
• Last Update Posted: December 27, 2021
• Sponsor: MedinCell S.A
• Information provided by (Responsible Party): MedinCell S.A

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Other
• Condition: Covid19
• Interventions: Drug: Ivermectin; Drug: Placebo
• Enrollment: 24

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)	Matching Placebo (Oral)
Arm/Group Description	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28	Placebo tablets matching the Active Investigative Medicinal Product (IMP)
Period Title: Overall Study
Started	6	6	6	6
Completed	6	6	5	6
Not Completed	0	0	1	0

Baseline Characteristics

Arm/Group Title		50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)	Matching Placebo (Oral)	Total
Arm/Group Description		Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28	Placebo tablets matching the Active IMP	Total of all reporting groups
Overall Number of Baseline Participants		6	6	6	6	24
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	24 participants
		35.2; (25 to 45)	29.3; (21 to 43)	30.3; (21 to 43)	28.2; (23 to 35)	30.8; (21 to 45)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	24 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	6 100.0%	6 100.0%	6 100.0%	6 100.0%	24 100.0%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants
						0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United Kingdom	Number Analyzed	6 participants	6 participants	6 participants	6 participants	24 participants
		6	6	6	6	24
Body Mass Index; Mean (Full Range); Unit of measure: Kg/m^2
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	24 participants
		24.95; (19.43 to 30.85)	25.79; (21.73 to 29.24)	25.84; (20.04 to 31.65)	25.57; (23.57 to 29.10)	25.54; (19.43 to 31.65)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Concentrations - (Maximum Plasma Concentration [Cmax])
Description	Maximum plasma concentration (Cmax)
Time Frame	D1, D2 and D28

Outcome Measure Data

Analysis Population Description

All 18 participants on active IMP were eligible and analyzed for this endpoint. Number Analyzed per Row represents those with data available at each time point.

Arm/Group Title		50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)
Arm/Group Description:		Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28
Overall Number of Participants Analyzed		6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
Day 1 after loading dose of 200mcg/kg (oral) for all active treatment groups	Number Analyzed	6 participants	6 participants	6 participants
		57.2; (28.9%)	41.7; (73.5%)	46.5; (53.6%)
Day 2 (first day on respective dose of active treatment)	Number Analyzed	6 participants	6 participants	6 participants
		22.3; (32.5%)	24.4; (42.5%)	33.2; (62.6%)
Day 28 (last day of active treatment)	Number Analyzed	6 participants	6 participants	5 participants
		23.3; (52.8%)	31.9; (27.6%)	44.4; (68.8%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mcg/kg (Oral), 75mcg/kg (Oral), 100mcg/kg (Oral)
	Comments	Assessment of dose proportionality on D2 and D28
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.803
	Comments	If the p-value is more than 0.05 then dose proportionality can not be confirmed.
	Method	Mixed Models Analysis
	Comments	[Not Specified]

2. Primary Outcome

Title	Pharmacokinetic Concentrations - (Time to Reach Cmax [Tmax])
Description	Time to reach Cmax (Tmax)
Time Frame	D1, D2 and D28

Outcome Measure Data

Analysis Population Description

All 18 participants on active IMP were eligible and analyzed for this endpoint. Number Analyzed per Row represents those with data available at each time point.

Arm/Group Title		50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)
Arm/Group Description:		Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28
Overall Number of Participants Analyzed		6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr
Day 1 after loading dose of 200mcg/kg (oral) for all active treatment groups	Number Analyzed	6 participants	6 participants	6 participants
		2.53; (36.8%)	3.03; (50.6%)	4.8; (47.2%)
Day 2 (first day on respective dose of active treatment)	Number Analyzed	6 participants	6 participants	6 participants
		3.82; (36.7%)	2.85; (38.8%)	3.23; (34.5%)
Day 28 (last day of active treatment)	Number Analyzed	6 participants	6 participants	5 participants
		2.83; (39.2%)	3.03; (50.7%)	3.03; (39.4%)

3. Primary Outcome

Title	Pharmacokinetic Concentrations - (Area Under the Plasma Concentration-time Curve From Zero to 24 Hours [AUC0-24hr])
Description	area under the plasma concentration-time curve from zero to 24 hours (AUC0-24hr) concentration-time curve from zero to 24 hours (AUC0-24hr)
Time Frame	D1, D2 and D28

Outcome Measure Data

Analysis Population Description

All 18 participants on active IMP were eligible and analyzed for this endpoint. Number Analyzed per Row represents those with data available at each time point.

Arm/Group Title		50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)
Arm/Group Description:		Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28
Overall Number of Participants Analyzed		6	6	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
Day 1 after loading dose of 200mcg/kg (oral) for all active treatment groups	Number Analyzed	6 participants	6 participants	6 participants
		568; (33.6%)	449; (62.0%)	523; (60.5%)
Day 2 (first day on respective dose of active treatment)	Number Analyzed	6 participants	6 participants	6 participants
		906; (31.4%)	779; (53.1%)	941; (59.0%)
Day 28 (last day of active treatment)	Number Analyzed	6 participants	6 participants	5 participants
		1.06; (36.6%)	1.5; (47.5%)	1.75; (20.6%)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	50mcg/kg (Oral), 75mcg/kg (Oral), 100mcg/kg (Oral)
	Comments	Assessment of dose proportionality on D2 and D28
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.689
	Comments	If the p-value is more than 0.05 then dose proportionality can not be confirmed.
	Method	Mixed Models Analysis
	Comments	[Not Specified]

4. Primary Outcome

Title	Pharmacokinetic Concentrations - (Apparent Terminal Half-Life [T1/2])
Description	apparent terminal half-life (t1/2)
Time Frame	D28

Outcome Measure Data

Analysis Population Description

17 participants on active IMP were analysed for this endpoint. On day 21 one subject in the 100 μg/kg/day ivermectin treatment group was discontinued.

Arm/Group Title	50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)
Arm/Group Description:	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28
Overall Number of Participants Analyzed	6	6	5
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr
	102; (60.1%)	99.2; (47.3%)	127; (47.2%)

5. Secondary Outcome

Title	Safety and Tolerability - Treatment Emergent Adverse Events (TEAEs)
Description	Clinical safety data from adverse event (AE) reporting
Time Frame	From Screening (Day -28) to Follow up visit (Day +42) plus 7 additional days.

Outcome Measure Data

Analysis Population Description

All 24 included participants were eligible and analysed for this endpoint

Arm/Group Title	50mcg/kg (Oral)	75mcg/kg (Oral)	100mcg/kg (Oral)	Matching Placebo (Oral)
Arm/Group Description:	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28	Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28	Placebo tablets matching the Active IMP
Overall Number of Participants Analyzed	6	6	6	6
Measure Type: Number; Unit of Measure: TEAE
Any TEAE	24	5	2	21
Any serious TEAE	0	0	0	0
Any TEAE leading to discontinuation - due to Study Medication-related TEAE	0	0	0	0
Any TEAE leading to discontinuation - other reason	0	0	1	0
TEAE - mild severity	24	5	2	20
TEAE - moderate severity	0	0	0	1
Causality (All TEAEs) - Not related	21	3	2	20
Causality (All TEAEs) - Related (possibly and probably)	3	2	0	1

Adverse Events

Time Frame

From Screening (Day -28) to Follow up visit (Day +42) plus 7 additional days

Adverse Event Reporting Description

[Not Specified]

Arm/Group Title

50mcg/kg (Oral)

75mcg/kg (Oral)

100mcg/kg (Oral)

Matching Placebo (Oral)

Ivermectin Overall

Total (Ivermectin Overall and Placebo)

Arm/Group Description

Ivermectin loading dose of 200 mcg/kg followed by daily doses of 50mcg/kg from D2 to D28.

Ivermectin loading dose of 200 mcg/kg followed by daily doses of 75mcg/kg from D2 to D28.

Ivermectin loading dose of 200 mcg/kg followed by daily doses of 100mcg/kg from D2 to D28.

Placebo tablets matching the Active IMP

Ivermectin loading dose of 200 mcg/kg followed by daily doses of either 50, 75, or 100mcg/kg from D2 to D28.

All study participants

All-Cause Mortality

50mcg/kg (Oral)

75mcg/kg (Oral)

100mcg/kg (Oral)

Matching Placebo (Oral)

Ivermectin Overall

Total (Ivermectin Overall and Placebo)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/18 (0.00%)

0/24 (0.00%)

Serious Adverse Events

50mcg/kg (Oral)

75mcg/kg (Oral)

100mcg/kg (Oral)

Matching Placebo (Oral)

Ivermectin Overall

Total (Ivermectin Overall and Placebo)

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/6 (0.00%)

0/18 (0.00%)

0/24 (0.00%)

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

0%

50mcg/kg (Oral)

75mcg/kg (Oral)

100mcg/kg (Oral)

Matching Placebo (Oral)

Ivermectin Overall

Total (Ivermectin Overall and Placebo)

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

6/6 (100.00%)

3/6 (50.00%)

2/6 (33.33%)

6/6 (100.00%)

11/18 (61.11%)

17/24 (70.83%)

Cardiac disorders

Palpitations † 1 [1]

1/6 (16.67%)

2

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

2/18 (11.11%)

3

2/24 (8.33%)

3

Gastrointestinal disorders

Diarrhoea † 1 [2]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Nausea † 1 [3]

3/6 (50.00%)

4

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

3/18 (16.67%)

4

4/24 (16.67%)

5

Toothache † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

General disorders

Chest discomfort † 1 [5]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

2

0/18 (0.00%)

0

1/24 (4.17%)

2

Infections and infestations

Oral herpes † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Injury, poisoning and procedural complications

Back injury † 1 [6]

0/6 (0.00%)

0

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Burns first degree † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Exposure to communicable disease † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Joint injury † 1 [6]

0/6 (0.00%)

0

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Limb injury † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Investigations

Transaminases increased † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Metabolism and nutrition disorders

Decreased appetite † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Dehydration † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Musculoskeletal and connective tissue disorders

Muscle twitching † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Myalgia † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Neck pain † 1 [6]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Nervous system disorders

Dizziness † 1 [7]

1/6 (16.67%)

1

1/6 (16.67%)

1

0/6 (0.00%)

0

1/6 (16.67%)

1

2/18 (11.11%)

2

3/24 (12.50%)

3

Headache † 1 [8]

3/6 (50.00%)

5

0/6 (0.00%)

0

1/6 (16.67%)

1

1/6 (16.67%)

1

4/18 (22.22%)

6

5/24 (20.83%)

7

Lethargy † 1 [9]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

2/6 (33.33%)

2

1/18 (5.56%)

1

3/24 (12.50%)

3

Paraesthesia † 1 [6]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Somnolence † 1 [10]

2/6 (33.33%)

2

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

2/18 (11.11%)

2

2/24 (8.33%)

2

Respiratory, thoracic and mediastinal disorders

Cough † 1 [11]

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Epistaxis † 1 [12]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

2/6 (33.33%)

2

0/18 (0.00%)

0

2/24 (8.33%)

2

Nasal congestion † 1 [6]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Oropharyngeal pain † 1 [10]

2/6 (33.33%)

2

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

2/18 (11.11%)

2

2/24 (8.33%)

2

Rhinorrhoea † 1 [6]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Skin and subcutaneous tissue disorders

Eczema † 1 [4]

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/6 (16.67%)

1

0/18 (0.00%)

0

1/24 (4.17%)

1

Pruritus † 1 [6]

1/6 (16.67%)

1

0/6 (0.00%)

0

0/6 (0.00%)

0

0/6 (0.00%)

0

1/18 (5.56%)

1

1/24 (4.17%)

1

Rash † 1 [13]

1/6 (16.67%)

1

1/6 (16.67%)

1

0/6 (0.00%)

0

1/6 (16.67%)

1

2/18 (11.11%)

2

3/24 (12.50%)

3

1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment; [1] 2 subjects on active treatment experienced 3 AEs; 2 AEs (one in each subject) were possibly related to study drug; [2] 1 subject on active treatment experienced 1 AE; it was possibly related to the study drug; [3] 3 subjects on active treatment experienced 4 AEs and 1 subject on placebo experienced 1 AE; 1 AE in the treatment group was possibly related to the study drug; [4] 1 subject on placebo experienced 1 AE; [5] 1 subject on placebo experienced 2 AEs; [6] 1 subject on active treatment experienced 1 AE; it was not related to the study drug; [7] 2 subjects on active treatment experienced 2 AEs and 1 subject on placebo experienced 1 AE; for 1 subject on active treatment and 1 subject on placebo it was possibly related to the study drug; [8] 4 subjects on active treatment experienced 6 AEs and one subject on placebo experienced 1 AE; none were related to the study drug; [9] 1 subject on active treatment experienced 1 AE and 2 subjects on placebo experienced 2 AEs; none were related to the study drug; [10] 2 subjects on active treatment experienced 2 AEs; they were not related to the study drug; [11] 1 subject on active treatment experienced 1 AE; it was unlikely related to the study drug; [12] 2 subjects on placebo experienced 2 AEs; [13] 2 subjects on active treatment experienced 2 AEs and 1 subject on placebo experienced 1 AE; none were related to the study drug

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The PI does not have the right to publish or otherwise present any results or data related to the study without an expressed written agreement from the Sponsor.

Results Point of Contact

• Name/Title: Joel Richard - Chief Development Officer
• Organization: MedinCell S.A.
• Phone: 00336984590 ext 99
• EMail: joel.richard@medincell.com

• Responsible Party: MedinCell S.A
• ClinicalTrials.gov Identifier: NCT04632706
• Other Study ID Numbers: mdc-TTG-CT-001
• First Submitted: October 26, 2020
• First Posted: November 17, 2020
• Results First Submitted: December 14, 2021
• Results First Posted: December 27, 2021
• Last Update Posted: December 27, 2021