NOVESA: A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Systemic Sclerosis

• Sponsor: Galapagos NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03798366
• Collaborator: (none)
• Enrollment: 33
• Locations: 18
• Arms: 2
• Actual Duration (Months): 17.2
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of the study is to see if GLPG1690 helps (together with the standard of care treatment) in the treatment of the skin and other areas affected by systemic sclerosis.

Another aim is to find out how safe/well tolerated GLPG1690 will be and whether there are any side effects. The study will also look at other things, including whether the study drug affects disease progression and also if it changes any aspect of the quality of life.

Condition or Disease	Intervention/Treatment	Phase
Systemic Sclerosis	Drug: GLPG1690; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered GLPG1690 for 24 Weeks in Subjects With Systemic Sclerosis
• Actual Study Start Date: Jan 14, 2019
• Actual Primary Completion Date: May 21, 2020
• Actual Study Completion Date: Jun 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GLPG1690 600 mg Participants received GLPG1690 600 milligrams (mg), orally once daily for 24 weeks.	Drug: GLPG1690; Film-coated tablets of GLPG1690 for oral use.
Placebo Comparator: Placebo Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.	Drug: Placebo; Film-coated tablets of GLPG1690 matching placebo for oral use.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in mRSS at Week 4 [Baseline, Week 4]

   The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.

2. Change From Baseline in mRSS at Week 8 [Baseline, Week 8]

   The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.

3. Change From Baseline in mRSS at Week 16 [Baseline, Week 16]

   The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.

4. Change From Baseline in mRSS at Week 24 [Baseline, Week 24]

   The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.

Secondary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [Baseline up to end of the study (36 weeks)]

   An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. A treatment-emergent adverse event (TEAE) is any AE with an onset date on or after the start of stud drug intake and no later than 30 days after last dose of study drug, or any worsening of any AE on or after the start of stud drug intake. A serious AE was defined as an AE that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically significant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to any screening evaluations.

• Male and female participants ≥18 years at the time of consent who meet the American College of Rheumatology (ACR)/EULAR 2013 diagnostic criteria for systemic sclerosis with diffuse cutaneous involvement (according to LeRoy's criteria) and ≤5 years since the onset of the first systemic sclerosis manifestation other than Raynaud's phenomenon.

• Modified Rodnan Skin Score (mRSS) >10 at screening.

• Active disease at screening, as defined by: Worsening of skin thickening (≥2 mRSS points) as assessed by mRSS measured at screening versus a previous mRSS assessment made within 6 months prior to screening, or new areas of skin involvement within 6 months prior to screening as documented by physician note, or new-onset systemic sclerosis with symptoms or signs other than Raynaud's phenomenon within 2 years prior to screening, or ≥1 tendon friction rub (palpated in the finger flexors or extensors, wrist flexors or extensors, olecranon bursa, shoulders, knees, anterior or posterior ankles with active motion).

• Participant must be able and willing to comply with restrictions on prior and concomitant medication as described in the protocol

• Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at the baseline visit.

• Female participants of childbearing potential or male participants with female partners of childbearing potential must be willing to comply with the contraceptive methods described in the protocol prior to the first dose of the investigational medicinal product (IMP), during the clinical study, and for at least 90 days after the last dose of the IMP for male participants and 30 days after the last dose of the IMP for female participants.

• A body mass index (BMI) between 18-35 kg/m^2, inclusive, at screening.

• Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and fasting clinical laboratory safety tests. Clinical laboratory safety test results must be within the reference ranges or test results that are outside the reference ranges need to be considered non-clinically significant in the opinion of the investigator.

Exclusion Criteria:

• Known hypersensitivity to IMP ingredients or history of a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.

• Breastfeeding female or participant intending to become pregnant or breastfeed.

• History of or a current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection, congenital, acquired).

• Positive blood testing for hepatitis B surface antigen or hepatitis C virus (antibody, confirmed by hepatitis C virus ribonucleic acid [RNA] positivity). Note: Participants with a resolved hepatitis A at least 3 months prior to screening can be screened.

• History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer medically managed through active surveillance or watchful waiting, and squamous cell carcinoma of the skin if fully resected and ductal carcinoma in situ).

• Clinically significant abnormalities, in the opinion of the investigator, detected on ECG at screening of either rhythm or conduction, QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms, or a known long QT syndrome.

• Unstable cardiovascular, pulmonary, or other disease (other than systemic sclerosis-related), in the opinion of the investigator, within 6 months prior to the baseline visit (e.g. coronary heart disease, heart failure, stroke).

• Severe pulmonary disease with forced vital capacity (FVC) ≤45% of predicted within 6 months prior to the baseline visit.

• Chronic or ongoing active infectious disease, including tuberculosis (requiring hospitalization or systemic treatment within 4 weeks prior to the baseline visit).

• Abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or bilirubin, and/or alkaline phosphatase >2x upper limit of normal (ULN). Retesting is allowed once.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Arthritis Care Center	Los Angeles	California	United States	90045
2	UCLA Rheumatology	Los Angeles	California	United States	90095
3	RASF Clinical Research Center	Boca Raton	Florida	United States	33486
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	Metroplex Clinical Research Center	Dallas	Texas	United States	75231
7	UT Physicians Center for Autoimmunity	Houston	Texas	United States	77030
8	UZ Gent	Gent		Belgium	9000
9	UZ Leuven	Leuven		Belgium	3000
10	Charité - Universitätsmedizin Berlin	Berlin		Germany	10117
11	Universitätsklinikum Frankfurt	Frankfurt		Germany	60590
12	Azienda Ospedaliero	Firenze		Italy	50439
13	Ospedale San Raffaele S.r.l. - PPDS	Milano		Italy	20132
14	Hospital Universitario Vall d'Hebron - PPDS	Barcelona		Spain
15	Hospital Universitario 12 de Octubre	Madrid		Spain
16	Hospital Nuestra Señora de Valme	Sevilla		Spain
17	University Hospital Aintree	Liverpool		United Kingdom	L9 7AL
18	Royal Free Hospital	London		United Kingdom	NW32QG

Sponsors and Collaborators

• Galapagos NV

Investigators

• Study Director: Galapagos Study Director, Galapagos NV

Study Documents (Full-Text)

• Study Protocol - Apr 28, 2020
• Statistical Analysis Plan - Aug 5, 2020

More Information

Publications

None provided.

• Responsible Party: Galapagos NV
• ClinicalTrials.gov Identifier: NCT03798366
• Other Study ID Numbers: GLPG1690-CL-204; 2018-001817-33
• First Posted: Jan 9, 2019
• Last Update Posted: May 4, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Belgium, the United States, United Kingdom, Spain, and Italy. The first participant was screened on 14 Jan 2019. The last study visit occurred on 22 Jun 2020.
Pre-assignment Detail	A total of 40 participants were screened, of whom 33 participants were randomized and treated.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 milligrams (mg), orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Period Title: Overall Study
STARTED	21	12
COMPLETED	21	11
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	GLPG1690 600 mg	Placebo	Total
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.	Total of all reporting groups
Overall Participants	21	12	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (13.58)	47.3 (17.99)	49.3 (15.13)
Sex: Female, Male (Count of Participants)
Female	15 71.4%	8 66.7%	23 69.7%
Male	6 28.6%	4 33.3%	10 30.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.8%	1 8.3%	2 6.1%
Not Hispanic or Latino	20 95.2%	10 83.3%	30 90.9%
Unknown or Not Reported	0 0%	1 8.3%	1 3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 8.3%	1 3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	21 100%	11 91.7%	32 97%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Modified Rodnan Skin Score (mRSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.0 (8.84)	22.5 (6.24)	25.3 (8.18)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in mRSS at Week 4
Description	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Participants in the FAS were analyzed.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Measure Participants	21	12
Least Squares Mean (Standard Error) [units on a scale]	-2.2 (0.85)	-1.6 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1690 600 mg, Placebo
	Comments	Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6757
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -3.1 to 2.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.29
	Estimation Comments	A negative difference indicates a greater improvement in the GLPG1690 treatment group.

2. Primary Outcome

Title	Change From Baseline in mRSS at Week 8
Description	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

Participants in the FAS were analyzed.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Measure Participants	21	12
Least Squares Mean (Standard Error) [units on a scale]	-3.2 (0.85)	-2.5 (1.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1690 600 mg, Placebo
	Comments	Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6079
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.3 to 1.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.31
	Estimation Comments	A negative difference indicates a greater improvement in the GLPG1690 treatment group.

3. Primary Outcome

Title	Change From Baseline in mRSS at Week 16
Description	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

Participants in the FAS were analyzed.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Measure Participants	21	12
Least Squares Mean (Standard Error) [units on a scale]	-6.8 (0.85)	-4.8 (1.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1690 600 mg, Placebo
	Comments	Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1298
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -4.8 to 0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.35
	Estimation Comments	A negative difference indicates a greater improvement in the GLPG1690 treatment group.

4. Primary Outcome

Title	Change From Baseline in mRSS at Week 24
Description	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants in the FAS were analyzed.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Measure Participants	21	12
Least Squares Mean (Standard Error) [units on a scale]	-8.9 (0.87)	-6.0 (1.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1690 600 mg, Placebo
	Comments	Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0411
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -5.6 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.36
	Estimation Comments	A negative difference indicates a greater improvement in the GLPG1690 treatment group.

5. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. A treatment-emergent adverse event (TEAE) is any AE with an onset date on or after the start of stud drug intake and no later than 30 days after last dose of study drug, or any worsening of any AE on or after the start of stud drug intake. A serious AE was defined as an AE that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically significant.
Time Frame	Baseline up to end of the study (36 weeks)

Outcome Measure Data

Analysis Population Description

Safety analysis set consisted of all randomized participants who received at least 1 dose of investigational product.

Arm/Group Title	GLPG1690 600 mg	Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.	Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
Measure Participants	21	12
TEAEs	20 95.2%	11 91.7%
Serious TEAEs	2 9.5%	1 8.3%

Adverse Events

Time Frame	Baseline up to end of the study (36 weeks)
Adverse Event Reporting Description	Participants in the safety analysis set were analyzed.
Arm/Group Title	GLPG1690 600 mg		Placebo
Arm/Group Description	Participants received GLPG1690 600 mg, orally once daily for 24 weeks.		Participants received GLPG1690 matching placebo, orally once daily for 24 weeks.
All Cause Mortality
	GLPG1690 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/12 (0%)
Serious Adverse Events
	GLPG1690 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/21 (9.5%)		1/12 (8.3%)
Infections and infestations
Sepsis	2/21 (9.5%)		0/12 (0%)
Device related infection	1/21 (4.8%)		0/12 (0%)
Pharyngitis	1/21 (4.8%)		0/12 (0%)
Injury, poisoning and procedural complications
Foreign body in gastrointestinal tract	0/21 (0%)		1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	GLPG1690 600 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)		11/12 (91.7%)
Blood and lymphatic system disorders
Anaemia	1/21 (4.8%)		0/12 (0%)
Cardiac disorders
Palpitations	2/21 (9.5%)		1/12 (8.3%)
Bundle branch block left	0/21 (0%)		1/12 (8.3%)
Ear and labyrinth disorders
Vertigo	1/21 (4.8%)		0/12 (0%)
Eye disorders
Vision blurred	1/21 (4.8%)		0/12 (0%)
Gastrointestinal disorders
Diarrhoea	7/21 (33.3%)		2/12 (16.7%)
Abdominal distension	2/21 (9.5%)		0/12 (0%)
Dyspepsia	2/21 (9.5%)		0/12 (0%)
Gastrooesophageal reflux disease	1/21 (4.8%)		1/12 (8.3%)
Oesophagitis	1/21 (4.8%)		1/12 (8.3%)
Abdominal pain	1/21 (4.8%)		0/12 (0%)
Aphthous ulcer	1/21 (4.8%)		0/12 (0%)
Constipation	1/21 (4.8%)		0/12 (0%)
Eructation	0/21 (0%)		1/12 (8.3%)
Gastric antral vascular ectasia	0/21 (0%)		1/12 (8.3%)
Gastrointestinal inflammation	1/21 (4.8%)		0/12 (0%)
Gingival recession	1/21 (4.8%)		0/12 (0%)
Nausea	1/21 (4.8%)		0/12 (0%)
General disorders
Peripheral swelling	3/21 (14.3%)		0/12 (0%)
Discomfort	0/21 (0%)		1/12 (8.3%)
Malaise	1/21 (4.8%)		0/12 (0%)
Pyrexia	0/21 (0%)		1/12 (8.3%)
Infections and infestations
Upper respiratory tract infection	2/21 (9.5%)		2/12 (16.7%)
Rhinitis	2/21 (9.5%)		1/12 (8.3%)
Urinary tract infection	3/21 (14.3%)		0/12 (0%)
Cellulitis	2/21 (9.5%)		0/12 (0%)
Influenza	2/21 (9.5%)		0/12 (0%)
Pharyngitis	2/21 (9.5%)		0/12 (0%)
Bronchitis	0/21 (0%)		1/12 (8.3%)
Conjunctivitis	1/21 (4.8%)		0/12 (0%)
Gastroenteritis	1/21 (4.8%)		0/12 (0%)
Gastroenteritis viral	1/21 (4.8%)		0/12 (0%)
Herpes zoster	1/21 (4.8%)		0/12 (0%)
Hordeolum	1/21 (4.8%)		0/12 (0%)
Nasopharyngitis	0/21 (0%)		1/12 (8.3%)
Oral herpes	0/21 (0%)		1/12 (8.3%)
Otitis media	1/21 (4.8%)		0/12 (0%)
Sinusitis	1/21 (4.8%)		0/12 (0%)
Suspected COVID-19	0/21 (0%)		1/12 (8.3%)
Injury, poisoning and procedural complications
Ligament sprain	1/21 (4.8%)		0/12 (0%)
Limb injury	1/21 (4.8%)		0/12 (0%)
Procedural pain	1/21 (4.8%)		0/12 (0%)
Skin abrasion	1/21 (4.8%)		0/12 (0%)
Tendon injury	1/21 (4.8%)		0/12 (0%)
Vascular injury	1/21 (4.8%)		0/12 (0%)
Investigations
Alanine aminotransferase increased	2/21 (9.5%)		0/12 (0%)
Weight increased	2/21 (9.5%)		0/12 (0%)
Aspartate aminotransferase increased	1/21 (4.8%)		0/12 (0%)
Blood lactate dehydrogenase increased	1/21 (4.8%)		0/12 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/21 (0%)		1/12 (8.3%)
Dyslipidaemia	1/21 (4.8%)		0/12 (0%)
Iron deficiency	1/21 (4.8%)		0/12 (0%)
Lactose intolerance	0/21 (0%)		1/12 (8.3%)
Vitamin D deficiency	0/21 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/21 (9.5%)		0/12 (0%)
Back pain	2/21 (9.5%)		0/12 (0%)
Bone disorder	1/21 (4.8%)		0/12 (0%)
Fibromyalgia	0/21 (0%)		1/12 (8.3%)
Muscular weakness	0/21 (0%)		1/12 (8.3%)
Musculoskeletal pain	1/21 (4.8%)		0/12 (0%)
Myalgia	0/21 (0%)		1/12 (8.3%)
Osteolysis	1/21 (4.8%)		0/12 (0%)
Pain in extremity	0/21 (0%)		1/12 (8.3%)
Scleroderma	1/21 (4.8%)		0/12 (0%)
Synovitis	1/21 (4.8%)		0/12 (0%)
Tendonitis	1/21 (4.8%)		0/12 (0%)
Tenosynovitis stenosans	1/21 (4.8%)		0/12 (0%)
Nervous system disorders
Headache	5/21 (23.8%)		2/12 (16.7%)
Dizziness	3/21 (14.3%)		1/12 (8.3%)
Dyskinesia	1/21 (4.8%)		0/12 (0%)
Memory impairment	1/21 (4.8%)		0/12 (0%)
Migraine	1/21 (4.8%)		0/12 (0%)
Psychiatric disorders
Insomnia	0/21 (0%)		2/12 (16.7%)
Anger	1/21 (4.8%)		0/12 (0%)
Renal and urinary disorders
Pollakiuria	1/21 (4.8%)		0/12 (0%)
Urinary incontinence	1/21 (4.8%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/21 (14.3%)		1/12 (8.3%)
Rhinorrhoea	1/21 (4.8%)		1/12 (8.3%)
Dyspnoea	1/21 (4.8%)		0/12 (0%)
Interstitial lung disease	1/21 (4.8%)		0/12 (0%)
Nasal congestion	1/21 (4.8%)		0/12 (0%)
Oropharyngeal pain	1/21 (4.8%)		0/12 (0%)
Sinus congestion	1/21 (4.8%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Skin lesion	4/21 (19%)		0/12 (0%)
Digital pitting scar	1/21 (4.8%)		1/12 (8.3%)
Hyperhidrosis	1/21 (4.8%)		1/12 (8.3%)
Skin ulcer	1/21 (4.8%)		1/12 (8.3%)
Acne	1/21 (4.8%)		0/12 (0%)
Hair growth abnormal	0/21 (0%)		1/12 (8.3%)
Hypertrichosis	1/21 (4.8%)		0/12 (0%)
Night sweats	0/21 (0%)		1/12 (8.3%)
Rash	0/21 (0%)		1/12 (8.3%)
Rash erythematous	1/21 (4.8%)		0/12 (0%)
Rash macular	0/21 (0%)		1/12 (8.3%)
Vascular disorders
Hot flush	0/21 (0%)		1/12 (8.3%)
Raynaud's phenomenon	1/21 (4.8%)		0/12 (0%)

Limitations/Caveats

This was a proof-of-concept study not sized or powered to confirm any treatment effect.

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Certain Agreements

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

The sponsor must review and approve any results of the study or abstracts for professional meetings prepared by the investigator(s). Published data must not compromise the objectives of the study. Data from individual study centers in multicenter studies must not be published separately.