A Phase 2a of RSLV-132 in Subjects With Systemic Lupus Erythematosus (SLE)

• Sponsor: Resolve Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02660944
• Collaborator: (none)
• Enrollment: 64
• Locations: 16
• Arms: 2
• Actual Duration (Months): 55.2
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study evaluates the impact of 13 bi-weekly intravenous infusions of RSLV-132 on the cutaneous manifestations in subjects with systemic lupus erythematosus.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: RSLV-132; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Double-blind, Placebo-Controlled Study of RSLV-132 in Subjects With Systemic Lupus Erythematosus (SLE)
• Actual Study Start Date: Jan 3, 2016
• Actual Primary Completion Date: May 28, 2020
• Actual Study Completion Date: Aug 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RSLV-132 10 mg/kg RSLV-132	Drug: RSLV-132; RNase-Fc fusion protein
Placebo Comparator: Placebo Saline placebo	Drug: Placebo; Saline placebo

Outcome Measures

Primary Outcome Measures

1. Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo. [Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169]

   Mean change from baseline (from baseline to Day 85; or baseline to Day 169) in CLASI activity scores (Last Observation Carried Forward [LOCF] post censoring values). The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.

Secondary Outcome Measures

1. Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score [Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169]

   Percentage of participants achieving a 50% improvement in CLASI activity score at Day 85 and Day 169 (LOCF post censoring due to use of exclusionary medications)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• CLASI score greater than or equal to 10 at Baseline

• Positive for one or more RNA autoantibodies

Exclusion Criteria:

1. severe, active central nervous system (CNS) involvement at Screening;

2. severe renal involvement at Screening (urine protein/creatinine ratio of >200 mg/mmol, or an estimated creatinine clearance of <30 mL/min);

3. use of cyclophosphamide within 3 months of the Baseline visit;

4. use of rituximab within 6 months of the Baseline visit;

5. use of belimumab within 3 months of the Baseline visit;

6. use of background medications within 1 month of Baseline in excess of: i. mycophenolate mofetil > 3 g/day; ii. azathioprine > 200 mg/day; iii. methotrexate > 25 mg/day; iv. hydroxychloroquine > 400 mg/day; v. prednisone (or equivalent) > 15 mg/day;

7. use of an intravenous steroid "pulse" within 2 months of Baseline;

8. use of an intramuscular steroid injection within 1 month of Baseline;

9. change in SLE medications within 1 month of Baseline;

10. the presence of a clinically significant infection in the judgement of the Investigator within seven days prior to the receipt of the first dose of study drug;

11. positive viral load test for hepatitis B, C, or HIV at Screening;

12. participation in another clinical trial with receipt of an investigational product within 3 months or 5 half- lives, of last administration (whichever is longer) from Baseline;

13. positive pregnancy test at Screening or at Baseline;

14. female subjects currently breast feeding at Baseline;

15. inability or unwillingness to comply with protocol-specified procedures which, in the opinion of the Investigator, would make the subject unsuitable for study participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TriWest Research Associates	El Cajon	California	United States	92020
2	University of California San Diego	La Jolla	California	United States	92093
3	Valerius Research Center	Los Alamitos	California	United States	90720
4	Wallace Rheumatic Study Center	Los Angeles	California	United States	90048
5	University of Colorado	Aurora	Colorado	United States	80045
6	Clinical Research of West Florida	Clearwater	Florida	United States	33765
7	Center for Rheumatology, Immunology and Arthritis	Fort Lauderdale	Florida	United States	33309
8	Alper Research	Naples	Florida	United States	34102
9	Northwell Health/ Division of Rheumatology	Great Neck	New York	United States	11042
10	Feinstein Institute for Medical Research	Manhasset	New York	United States	11030
11	DJL Clinical Research	Charlotte	North Carolina	United States	28210
12	Cleveland Clinic	Cleveland	Ohio	United States	44195
13	Temple University	Philadelphia	Pennsylvania	United States	19140
14	Vanderbilt University	Nashville	Tennessee	United States	37232
15	Metroplex Clinical Research Center	Dallas	Texas	United States	75231
16	Accurate Clinical Research	Sugar Land	Texas	United States	77479

Sponsors and Collaborators

• Resolve Therapeutics

Investigators

• Study Chair: James Posada, Ph.D., Resolve Therapeutics

Study Documents (Full-Text)

• Study Protocol - Apr 27, 2017
• Statistical Analysis Plan - Mar 10, 2020

More Information

Publications

None provided.

• Responsible Party: Resolve Therapeutics
• ClinicalTrials.gov Identifier: NCT02660944
• Other Study ID Numbers: 132-03
• First Posted: Jan 21, 2016
• Last Update Posted: Mar 10, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic

Study Results

Participant Flow

Arm/Group Title	RSLV-132	Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo
Period Title: Overall Study
STARTED	42	22
COMPLETED	25	12
NOT COMPLETED	17	10

Baseline Characteristics

Arm/Group Title	RSLV-132	Placebo	Total
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo	Total of all reporting groups
Overall Participants	42	22	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.3 (12.8)	45.2 (11.6)	45.3 (12.3)
Sex: Female, Male (Count of Participants)
Female	39 92.9%	22 100%	61 95.3%
Male	3 7.1%	0 0%	3 4.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 31%	4 18.2%	17 26.6%
Not Hispanic or Latino	29 69%	18 81.8%	47 73.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.4%	0 0%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 38.1%	11 50%	27 42.2%
White	22 52.4%	11 50%	33 51.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 7.1%	0 0%	3 4.7%
Region of Enrollment (participants) [Number]
United States	32 76.2%	22 100%	54 84.4%
CLASI Activity Total Score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	24.1 (9.9)	22.4 (7.9)	23.5 (9.2)
Oral corticosteroid dose (Count of Participants)
0	20 47.6%	7 31.8%	27 42.2%
>0 and less than or equal to 7.5 mg/kg	6 14.3%	5 22.7%	11 17.2%
>7.5	16 38.1%	10 45.5%	26 40.6%

Outcome Measures

1. Primary Outcome

Title	Mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Improvement Compared to Placebo.
Description	Mean change from baseline (from baseline to Day 85; or baseline to Day 169) in CLASI activity scores (Last Observation Carried Forward [LOCF] post censoring values). The CLASI is a single-page tool that separately quantifies disease activity and damage. For the activity score, points are given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. The total score represents the sum of the individual scores and ranges from 0 to 70. Higher scores are awarded for more severe manifestations.
Time Frame	Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RSLV-132	Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo
Measure Participants	42	22
Day 85	-6.2 (6.7)	-6.5 (6.2)
Day 169	-6.2 (8.5)	-5.7 (7.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RSLV-132, Placebo
	Comments	Change from baseline at Day 85 RSLV-132 versus placebo
	Type of Statistical Test	Superiority
	Comments	Two-sample t-test with Satterthwaite approximation
Statistical Test of Hypothesis	p-Value	0.845
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -3.42 to 4.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RSLV-132, Placebo
	Comments	Change from baseline at Day 169 RSLV-132 versus placebo
	Type of Statistical Test	Superiority
	Comments	Two-sample t-test with Satterthwaite approximation
Statistical Test of Hypothesis	p-Value	0.818
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -4.66 to 3.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Achieving a 50% Improvement in CLASI Activity Score
Description	Percentage of participants achieving a 50% improvement in CLASI activity score at Day 85 and Day 169 (LOCF post censoring due to use of exclusionary medications)
Time Frame	Baseline and Days 29, 57, 85, 99, 113, 127, 141, 155, 169

Outcome Measure Data

Analysis Population Description

On Day 169, a post hoc exploratory subgroup analysis was performed on participants with severe CLASI and severe SLE Disease Activity Index (SLEDAI-2K) scores at baseline. The SLEDAI-2K is a clinical index for the assessment of lupus disease activity in the previous 30 days. It consists of 24 weighted clinical and laboratory variables of nine organ systems. Scores of the descriptors range from 1 to 8, the total possible score is 105. A higher score indicates more severe disease.

Arm/Group Title	RSLV-132	Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo
Measure Participants	42	22
Day 85	11 26.2%	2 9.1%
Day 169 All Participants	14 33.3%	5 22.7%
Day 169 Participants with Severe CLASI >/=21	7 16.7%	3 13.6%
Day 169 Participants with Severe SLEDAI >/=9	4 9.5%	1 4.5%

3. Post-Hoc Outcome

Title	Percentage of Participants With SRI-4 Response
Description	Percentage of participants with an Systemic Lupus Erythematous Responder Index (SRI) 4 response on Day 169. This is a composite responder index incorporating the British Isles Lupus Assessment Group (BILAG) 2004, SLEDAI-2K and Physician Global Assessment (PGA) responses. The BILAG-2004 index, an organ-based transitional activity instrument, provides disease activity scorings across nine organ systems (constitutional, mucocutaneous, neuropsychiatry, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological) on an ordinal scale (A to E) based on the physician's intention-to-treat premise. Grade A represents the most active and Grade E the least active disease. The Physician's Global Assessment is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

A subgroup analysis was also performed on participants with severe CLASI and severe SLEDAI scores

Arm/Group Title	RSLV-132	Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo
Measure Participants	42	22
Day 169 All participants	11 26.2%	7 31.8%
Day 169 Participants with Severe CLASI >/=21	7 16.7%	1 4.5%
Day 169 Participants with Severe SLEDAI >/=9	8 19%	4 18.2%

4. Post-Hoc Outcome

Title	Percentage of Participants With a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response
Description	Percentage of participants with a BICLA response on Day 169. This is a composite responder index incorporating the BILAG-2004, SLEDAI-2K and PGA responses. The BILAG-2004 index, an organ-based transitional activity instrument, provides disease activity scorings across nine organ systems (constitutional, mucocutaneous, neuropsychiatry, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological) on an ordinal scale (A to E) based on the physician's intention-to-treat premise. Grade A represents the most active and Grade E the least active disease. The PGA is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity.
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

A subgroup analysis was also performed on participants with severe CLASI and severe SLEDAI scores

Arm/Group Title	RSLV-132	Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein	Saline placebo Placebo: Saline placebo
Measure Participants	42	22
Day 169 All Participants	10 23.8%	4 18.2%
Day 169 Participants with Severe CLASI >/=21	5 11.9%	1 4.5%
Day 169 Participants with Severe SLEDAI >/=9	4 9.5%	1 4.5%

Adverse Events

Time Frame	215 days
Adverse Event Reporting Description	Treatment emergent adverse events are summarized
Arm/Group Title	RSLV-132		Placebo
Arm/Group Description	10 mg/kg RSLV-132 RSLV-132: RNase-Fc fusion protein		Saline placebo Placebo: Saline placebo
All Cause Mortality
	RSLV-132		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/22 (0%)
Serious Adverse Events
	RSLV-132		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/42 (7.1%)		5/22 (22.7%)
Gastrointestinal disorders
Colitis	0/42 (0%)	0	1/22 (4.5%)	1
Diarrhoea	0/42 (0%)	0	1/22 (4.5%)	1
Infections and infestations
Appendicitis	1/42 (2.4%)	1	1/22 (4.5%)	1
Escherichia Sepsis	0/42 (0%)	0	1/22 (4.5%)	1
Pneumonia	0/42 (0%)	0	1/22 (4.5%)	1
Urinary Tract Infection	0/42 (0%)	0	1/22 (4.5%)	1
Flank Pain	0/42 (0%)	0	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus	0/42 (0%)	0	1/22 (4.5%)	2
Nervous system disorders
Hypoaesthesia	1/42 (2.4%)	1	0/22 (0%)	0
Syncope	0/42 (0%)	0	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Cutaneous Lupus Erythematosus	1/42 (2.4%)	1	0/22 (0%)	0
Vascular disorders
Hypertension	0/42 (0%)	0	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	RSLV-132		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/42 (85.7%)		20/22 (90.9%)
Gastrointestinal disorders
Nausea	5/42 (11.9%)	5	2/22 (9.1%)	3
Infections and infestations
Urinary Tract Infection	4/42 (9.5%)	5	4/22 (18.2%)	4
Sinusitis	4/42 (9.5%)	4	0/22 (0%)	0
Upper Respiratory Tract Infection	3/42 (7.1%)	4	4/22 (18.2%)	5
Bronchitis	2/42 (4.8%)	2	2/22 (9.1%)	2
Musculoskeletal and connective tissue disorders
Systemic Lupus Erythematosus	1/42 (2.4%)	1	4/22 (18.2%)	4
Back Pain	1/42 (2.4%)	1	2/22 (9.1%)	2
Nervous system disorders
Headache	6/42 (14.3%)	7	3/22 (13.6%)	4
Renal and urinary disorders
Proteinuria	3/42 (7.1%)	4	0/22 (0%)	0
Dysuria	1/42 (2.4%)	1	2/22 (9.1%)	2
Skin and subcutaneous tissue disorders
Cutaneous Lupus Erythematosus	4/42 (9.5%)	5	0/22 (0%)	0
Rash	2/42 (4.8%)	2	2/22 (9.1%)	2
Vascular disorders
Hypertension	6/42 (14.3%)	6	4/22 (18.2%)	4

Limitations/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.