Phase 2 Study of RSLV-132 in Subjects With Long COVID

• ClinicalTrials.gov Identifier: NCT04944121
• Recruitment Status: Recruiting
• First Posted: June 29, 2021
• Last Update Posted: May 10, 2022
• Sponsor: Resolve Therapeutics
• Information provided by (Responsible Party): Resolve Therapeutics

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy (decrease in profound fatigue), safety and pharmacokinetics of RSLV-132 in subjects with long Corona Virus (COVID) syndome

Condition or disease	Intervention/treatment	Phase
Post-acute Corona Virus 19 (COVID-19) (Long COVID)	Drug: RSLV-132; Drug: Sodium Chloride 0.9%	Phase 2

Detailed Description:

This is a double-blind placebo-controlled study in approximately 70 subjects with long COVID syndrome. After being informed about the study and potential risks, all subjects giving written informed consent will be screened to determine eligibility in the 21 days before the start of study treatment. Prior to the first study treatment administration, subjects will be randomized in a 2:1 ratio to receive six administrations of 10 mg/kg RSLV-132 or placebo on Days 1, 8, 15, 29, 43 and 57. Subjects will then attend an end of study visit approximately 10 weeks after the start of treatment (Day 71).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Post-acute COVID-19 (Long COVID)
• Actual Study Start Date: June 25, 2021
• Estimated Primary Completion Date: March 31, 2023
• Estimated Study Completion Date: March 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: RSLV-132; RSLV-132 is an enzymatically active ribonuclease designed to digest the ribonucleic acid contained in autoantibodies and immune complexes and thereby render them biologically inert. A dose of 10 mg/kg will be administered by intravenous infusion on Days: 1, 8, 15, 29, 43, and 57	Drug: RSLV-132; 10 mg/kg RSLV-132 administered by intravenous infusion
Placebo Comparator: Placebo; Sodium chloride 0.9% will be administered by intravenous infusion on Days: 1, 8, 15, 29, 43, and 57	Drug: Sodium Chloride 0.9%; 0.9% sodium chloride administered by intravenous infusion

Outcome Measures

Primary Outcome Measures :

1. PROMIS Fatigue SF 7a T-score [ Time Frame: From Baseline to Day 71 ]
   Mean change in Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue 7a) T-score at the end of treatment compared to baseline. The PROMIS Fatigue 7a consists of seven questions measuring symptoms severity at five-point intervals, with higher scores representing a worse outcome.

Secondary Outcome Measures :

1. FACIT Fatigue questionnaire [ Time Frame: From Baseline to Day 71 ]
   Comparison of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire at the end of treatment compared to baseline. The FACIT-F is a 13 item measure of fatigue with a 7 day recall memory. Items are scored on a five point scale (0-not at all to 4-very much). The total score therefore ranges from 0 to 52, with higher scores reflecting greater fatigue.
2. Long COVID-19-related Symptom Assessment patient questionnaire [ Time Frame: From Baseline to Day 71 ]
   Comparison of the Long COVID-19-related Symptom Assessment patient questionnaire at the end of treatment compared to baseline. Subjects will be asked to describe the severity of eight COVID-19 related symptoms (muscle pain, joint pain, chest pain, brain fog, chills, sweats, abdominal pain and chest tightness) over the last 7 days on a four point scale (0-none to 3-severe) with a higher score representing a worse outcome.
3. Patient-reported Global Impression of Severity questionnaire [ Time Frame: From Baseline to Day 71 ]
   Comparison of the Patient-reported Global Impression of Severity (PGIS) questionnaire at the end of treatment compared to baseline. Subjects will be asked to describe the severity of fatigue on the assessment day compared to the past 7 days on a four point scale (1-no improvement to 4-significant improvement) with a higher score representing a better outcome.
4. Digit Symbol Substitution Test [ Time Frame: From Baseline to Day 71 ]
   Comparison of the Digit Symbol Substitution Test (DSST) at the end of treatment compared to baseline. The DSST is a highly validated measure of the patient's ability to focus and concentrate of a simple task. Subjects with profound fatigue take more time to complete the test.
5. Physician Global Assessment [ Time Frame: From Baseline to Day 71 ]
   Comparison of the Physician Global Assessment at the end of treatment compared to baseline. The 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by qualitative Polymerase Chain Reaction (PCR) at least 24 weeks prior to Baseline
• PROMIS Fatigue SF 7a raw score of 21 or greater at Screening (confirm onset of fatigue was post-infection)
• Able to communicate and able to provide valid, written informed consent
• Ages 18 to 75 inclusive
• Minimum weight of 45 kg
• Female participants shall be either of non-child-bearing potential (permanently sterilized by bilateral tubal occlusion, hysterectomy, or bilateral salpingectomy), or menopausal (more than one year since last menstrual cycle and confirmed by blood FSH levels > 22 mIU/mL) OR practicing highly effective contraception (e.g., oral (but not including progestogen-only oral contraceptives), injectable, implantable or transdermal contraceptives, a non-hormonal intrauterine device [IUD] or an intrauterine hormone releasing system [IUS]) for at least 2 months prior to dosing and until 125 days after the last dose. In terms of sexual relations, female participants not practicing highly effective contraception as described above should abstain or only engage with male partners who are sterile or vasectomized. Female participants of child-bearing potential will also be required to have a negative serum pregnancy test [beta human chorionic gonadotropin [ß-hCG]) at Screening and negative pregnancy urine test at Baseline. Female participants must agree not to donate eggs from the first dose until 125 days after the last dose
• Male participants, who are not sterile or vasectomized, must agree to abstain or only engage with female partners who use highly effective contraception from the first dose until 125 days after the last dose. Male participants must also agree not to donate sperm from the first dose until 125 days after the last dose

Exclusion Criteria:

• Previous admission to the intensive care unit for COVID-19-related symptoms
• Presence of orthostatic hypotension or tachycardia at Screening
• Completion of COVID-19 vaccination less than 4 weeks of Baseline (i.e., 4 weeks after the second dose of a two-dose vaccine or 4 weeks after a single dose vaccine)
• Use of therapies to treat COVID-19 symptoms such as remdesivir, dexamethasone (or any other corticosteroid), or convalescent plasma within 14 days of Baseline
• Use of concomitant medications that are sedating
• Screening lab abnormalities that may cause fatigue such as severe anemia or hypocalcaemia
• History of anaphylaxis to a medication, diet, or environmental exposure such as bee sting
• Previous diagnosis of chronic fatigue syndrome, fibromyalgia, lupus, Sjogren's syndrome, or postural orthostatic tachycardia syndrome (POTS)
• Previous diagnosis of sleep apnea
• Participation in another clinical study with receipt of an investigational product within 3 months or 5 half- lives, of last administration (whichever is longer) from Baseline
• The presence of a clinically significant infection in the judgement of the Investigator, within seven days of Baseline
• Positive test for hepatitis B, C, or HIV at Screening
• Positive pregnancy test at Screening or Baseline
• Female subjects currently pregnant or breast feeding at Baseline
• 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

Contacts

Contact: James Posada, PhD; (208) 727 7010; jp@resolvebio.com

Locations

United States, Alabama

Resolve Clinical Center; Terminated

Mobile, Alabama, United States, 36608

United States, Florida

Resolve Clinical Center; Terminated

Coral Gables, Florida, United States, 33134

Resolve Clinical Center; Recruiting

Pompano Beach, Florida, United States, 33060

Contact: Jordan Herman jordan@floridacrc.com

United States, Tennessee

Resolve Clinical Center; Recruiting

Knoxville, Tennessee, United States, 37920

Contact: Talya Thomas talya.thomas@amrllc.com

United States, Washington

Resolve Clinical Center; Recruiting

Seattle, Washington, United States, 98103

Contact covidresearchcenter@fredhutch.org

Sponsors and Collaborators

Resolve Therapeutics

Investigators

• Study Director: James Posada; Resolve Therapeutics LLC

More Information

• Responsible Party: Resolve Therapeutics
• ClinicalTrials.gov Identifier: NCT04944121
• Other Study ID Numbers: 132-05
• First Posted: June 29, 2021
• Last Update Posted: May 10, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases