Trial Outcomes & Findings for A Study to Investigate Safety of GS-248 and Efficacy on Raynauds' Phenomenon in Systemic Sclerosis (NCT NCT04744207)

NCT ID: NCT04744207

Last Updated: 2024-08-09

Results Overview

Patient reported number of Raynaud's attacks per day as registered in electronic diary.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 94 participants
• Primary outcome timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively
• Results posted on: 2024-08-09

Participant Flow

In addition to fulfilling all eligibility criteria, subjects must fulfil the following criteria to be randomised: •≥7 RP attacks during the last week of the run-in period as captured in the eDiary, with no more than 2 days without RP attacks. •Compliance with the eDiary during the 7 most recent days prior to baseline (Visit 2), excluding the visit day itself, defined as having submitted ≥5 days of eDiary records (out of a possible 7 days) for RCS and RP during that period.

The run-in period was 14-21 days prior to Day 1, Baseline visit (the first dose of IMP). Of the 94 subjects enrolled into the study 69 subjects met the eligiblity criteria for randomization after the run-in period and were assigned to a treatment group.

Participant milestones

Measure	GS-248 Participants received GS-248, (supplied as 40 mg capsules) Each single dose consisted of 3 capsules constituting a total of 120 mg, once daily for 4 weeks GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo Participants received placebo, (supplied as 3 capsules), once daily for 4 weeks Placebo: capsule, once daily for 4 weeks
Treatment STARTED	33	36
Treatment COMPLETED	30	34
Treatment NOT COMPLETED	3	2
Follow-up STARTED	30	34
Follow-up COMPLETED	30	34
Follow-up NOT COMPLETED	0	0

Reasons for withdrawal

Measure	GS-248 Participants received GS-248, (supplied as 40 mg capsules) Each single dose consisted of 3 capsules constituting a total of 120 mg, once daily for 4 weeks GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo Participants received placebo, (supplied as 3 capsules), once daily for 4 weeks Placebo: capsule, once daily for 4 weeks
Treatment Withdrawal by Subject	2	0
Treatment Adverse Event	1	2

Baseline Characteristics

A Study to Investigate Safety of GS-248 and Efficacy on Raynauds' Phenomenon in Systemic Sclerosis

Baseline characteristics by cohort

Measure	GS-248 n=33 Participants Participants received GS-248, (supplied as 40 mg capsules) Each single dose consisted of 3 capsules constituting a total of 120 mg, once daily for 4 weeks GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Participants received placebo, (supplied as 3 capsules), once daily for 4 weeks Placebo: capsule, once daily for 4 weeks	Total n=69 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=93 Participants	32 Participants n=4 Participants	62 Participants n=27 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants
Age, Continuous	49.0 years STANDARD_DEVIATION 10.6 • n=93 Participants	50.6 years STANDARD_DEVIATION 10.6 • n=4 Participants	49.8 years STANDARD_DEVIATION 10.5 • n=27 Participants
Sex: Female, Male Female	27 Participants n=93 Participants	33 Participants n=4 Participants	60 Participants n=27 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	3 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	30 Participants n=93 Participants	34 Participants n=4 Participants	64 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment Netherlands	2 participants n=93 Participants	3 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Belgium	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Region of Enrollment Poland	17 participants n=93 Participants	20 participants n=4 Participants	37 participants n=27 Participants
Region of Enrollment United Kingdom	12 participants n=93 Participants	12 participants n=4 Participants	24 participants n=27 Participants
Stratification factors FAS Ca-blockers	18 Participants n=93 Participants	19 Participants n=4 Participants	37 Participants n=27 Participants
Stratification factors FAS PDE-5 inhibitors	9 Participants n=93 Participants	10 Participants n=4 Participants	19 Participants n=27 Participants
Stratification factors FAS No treatment	6 Participants n=93 Participants	7 Participants n=4 Participants	13 Participants n=27 Participants

PRIMARY outcome

Timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

Patient reported number of Raynaud's attacks per day as registered in electronic diary.

Outcome measures

Measure	GS-248 n=33 Participants GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Placebo: capsule, once daily for 4 weeks
Mean Change From Baseline to Week 4 in the Number of Raynaud Attacks Per Week.	-3.41 number of attacks Interval -5.83 to -0.99	-4.22 number of attacks Interval -6.48 to -1.96

SECONDARY outcome

Timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

Patients reported Raynaud's Condition Score (RCS) once a day in an electronic diary.

RCS is a validated numeric rating scale (from 0 to 10) answering the question "What difficulty did you have today with your Raynaud's condition?" where a score of '0' = 'No difficulty', and a score of '10' = 'Extreme difficulty'.

Outcome measures

Measure	GS-248 n=33 Participants GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Placebo: capsule, once daily for 4 weeks
Mean Change From Baseline to Week 4 in the Raynaud's Condition Score.	-0.99 score Interval -1.54 to -0.45	-0.95 score Interval -1.45 to -0.46

SECONDARY outcome

Timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

The patient reported the experienced pain of each Raynaud attack using a Numeric Rating Scale (NRS) from 0 to 10 in an electronic diary where '0'='No pain' and '10'='Worst imaginable pain'.

Outcome measures

Measure	GS-248 n=33 Participants GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Placebo: capsule, once daily for 4 weeks
Mean Change From Baseline to Week 4 in Pain Experienced During Raynaud Attacks.	-0.65 numeric rating scale Interval -1.16 to -0.14	-0.60 numeric rating scale Interval -1.07 to -0.13

SECONDARY outcome

Timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

Outcome measures

Measure	GS-248 n=33 Participants GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Placebo: capsule, once daily for 4 weeks
Mean Change From Baseline to Week 4 in the Mean Duration of Raynaud's Attacks	1.06 LN (minutes); back-transformed Interval 0.87 to 1.29	0.89 LN (minutes); back-transformed Interval 0.74 to 1.08

SECONDARY outcome

Timeframe: From baseline to week 4, i.e. the 7 most recent days prior to Visit 2 and Visit 4 respectively

The patient reported the start time (hh:mm) and stop time (hh:mm) of each Raynaud's attack in the electronic diary.

Outcome measures

Measure	GS-248 n=33 Participants GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 Participants Placebo: capsule, once daily for 4 weeks
Mean Change From Baseline to Week 4 in the Cumulative Duration of Raynaud Attacks.	0.70 LN (minutes); back-transformed Interval 0.51 to 0.98	0.61 LN (minutes); back-transformed Interval 0.45 to 0.82

Adverse Events

GS-248

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Measure	GS-248 n=33 participants at risk Participants received GS-248, (supplied as 40 mg capsules) Each single dose consisted of 3 capsules constituting a total of 120 mg, once daily for 4 weeks GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 participants at risk Participants received placebo, (supplied as 3 capsules), once daily for 4 weeks Placebo: capsule, once daily for 4 weeks
Injury, poisoning and procedural complications Thermal burn	0.00% 0/33 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	2.8% 1/36 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).
Infections and infestations Sepsis	0.00% 0/33 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	2.8% 1/36 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).

Other adverse events

Measure	GS-248 n=33 participants at risk Participants received GS-248, (supplied as 40 mg capsules) Each single dose consisted of 3 capsules constituting a total of 120 mg, once daily for 4 weeks GS-248: 120 mg, capsule, once daily for 4 weeks	Placebo n=36 participants at risk Participants received placebo, (supplied as 3 capsules), once daily for 4 weeks Placebo: capsule, once daily for 4 weeks
Investigations White blood cell count decreased	0.00% 0/33 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	5.6% 2/36 • Number of events 2 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).
Nervous system disorders Headache	18.2% 6/33 • Number of events 18 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	11.1% 4/36 • Number of events 5 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).
Gastrointestinal disorders Abdominal pain upper	6.1% 2/33 • Number of events 2 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	0.00% 0/36 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).
Gastrointestinal disorders Nausea	6.1% 2/33 • Number of events 2 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	2.8% 1/36 • Number of events 1 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/33 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).	8.3% 3/36 • Number of events 4 • All AEs and SAEs were collected during the full study period from the signing of the ICF until the last study visit (2-3 weeks run-in period, 4 weeks treatment period and 2-3 weeks follow-up period; i.e. 8-10 weeks).

Additional Information

Study Director

Gesynta Pharma AB

Phone: +46 73 386 4246

Email: ctg@gesynta.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place