Safety and Efficacy of FSD201 for the Treatment of Chronic Pain Associated With Idiopathic MCAS (MCAD)

Mast Cell Activation Syndrome Clinical Trial

Official title:

A Randomized, Double-Blind Placebo Controlled Parallel Group Study of Safety and Efficacy of FSD201 in Patients With Chronic Widespread Musculoskeletal Nociplastic Pain Associated With Idiopathic Mast Cell Activation Syndrome (Disorder)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05652907
• Other study ID #: FSD201-010
• Status: Terminated
• Phase: Phase 2
• Start date: January 19, 2023
• Est. completion date: May 24, 2023

Study information

• Verified date: February 2023
• Source: FSD Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will determine if FSD201 reduces the average daily 24-hour recall pain intensity after 28 and 56 days of treatment in adults with chronic widespread musculoskeletal nociplastic pain.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 24, 2023
• Est. primary completion date: May 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Clinical diagnosis of idiopathic MCAS as per the global consensus diagnostic criteria

• Adults with widespread chronic pain (in three or more body regions);

• Chronic pains of intensity greater than or equal to 4.0 but less than or equal to 9.0 on a Numeric Pain Rating Scale, symptom duration of more than 6 months;

• Subject agrees to use only acetaminophen (up to 1000 mg per dose and not to exceed 3000 mg/day) or diphenhydramine (up to 300 mg/day) as rescue medication for chronic widespread musculoskeletal nociplastic pains throughout the trial;

• The subject is willing to maintain current activity and exercise levels throughout the study;

• During the study, the subject agrees not to initiate or change any non-pharmacologic interventions (including chiropractic care, physical therapy, psychotherapy, and massage therapy). Any ongoing non-pharmacologic intervention must be stable for at least 4 weeks before screening and should be continued for the duration of the study;

Key Exclusion Criteria:

• The subject has pain that cannot be clearly differentiated from or that could interfere with the assessment of chronic musculoskeletal nociplastic pain secondary likely to idiopathic MCAS (post-herpetic neuralgia, traumatic injury, prior surgery, complex regional pain syndrome);

• Adults with chronic cancer pain;

• Adults with inflammatory connective tissue disorder or rheumatological disorder-related pain, for example rheumatoid arthritis;

• Adults with focal musculoskeletal pain;

• Adults with skin diseases (chronic urticaria, pemphigus, lupus, rosacea etc.);

• Adults with endocrinological disorders (acute hypothyroidism, acute adrenal insufficiency etc.);

• Adults with systemic gastrointestinal conditions (Inflammatory bowel disorders);

• Significant psychological comorbidities: PHQ-9 score greater than 20; and GAD-7 score greater than 15 (indication of severe anxiety that could interfere with accurate logging of pain ratings);

• Current or recent (within 12 months of screening) history of a substance use disorder including cannabinoid or alcohol use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5);

• Subject has neurologic disorder unrelated to chronic widespread musculoskeletal nociplastic pains (phantom limb from amputation, vitamin B12 deficiency, chronic inflammatory demyelinating polyneuropathy), circulatory disorder (peripheral artery disease), a skin condition in the area of neuropathy that could alter sensation (plantar ulcer), or other painful conditions (arthritis) that could interfere with reporting of pain due to chronic widespread musculoskeletal nociplastic pains;

• Current severe or uncontrolled major depressive disorder or anxiety disorders. Mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study. Stable doses of SSRIs are allowed for the treatment of depression if the dose is stable for 60 days before Screening Visit;

• Subject has a history of suicide attempt or suicidal behaviour within the last 12 months or has suicidal ideation within the previous 12 months or who is at significant risk to commit suicide, as judged by the Investigator at Screening and/or Randomization Visit;

• Patients with active malignancy or history of malignancy, except for basal cell or squamous cell carcinoma and actinic keratosis. Basal cell carcinoma and small squamous cell carcinoma of the skin which have been excised according to guidelines within the last 5 years or in situ cervical carcinoma that has been fully treated and shows no evidence of recurrence are allowed;

• Individuals with generalized joint hypermobility secondary to hereditary connective tissue disorders like Ehlers Danlos Syndrome;

• Individuals with high baseline serum tryptase levels suggestive of Primary or Secondary MCAS (defined as above the normal range of 2.2 to 13.2 µg/L).

Related Conditions & MeSH terms

• Mast Cell Activation Syndrome
• Syndrome

Intervention

Drug:
• FSD201
Tablets for oral administration.
• Placebo
Placebo tablets matched to FSD201 for oral administration.

Locations

Country	Name	City	State
Canada	Toronto Rehabilitation Institute	Toronto	Ontario
United States	Norman Marcus Pain Institute	New York	New York
United States	Saint Charles Clinical Research	Weldon Spring	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
FSD Pharma, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Targeted treatment effect of 30% decrease from baseline to Day 28 in the average daily pain intensity	Targeted treatment effect of 30% decrease from baseline to Day 28 in the average daily pain intensity score measured by an 11-point numerical pain rating scale (NPRS). NPRS is an 11-point scale from 0 to10 where the higher number indicates worse pain.; Averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1 Day 28: calculated weekly average from Day 22 to Day 28	Day 28
Secondary	Percentage of subjects achieving =30% reduction in Numerical Pain Rating Scale (NPRS) score at the end of treatment with FSD201 at the end of treatment with FSD201	Change from baseline in the weekly average of the average daily pain intensity measured by Numerical Pain Rating Scale (NPRS). NPRS is an 11-point scale from 0 to 10 where the higher number indicates worse pain.; NPRS averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1 Day 28: calculated weekly average from Day 22 to Day 28 Day 56: calculated weekly average from Day 49 to Day 55 for the NPRS.	Day 28, Day 56
Secondary	Change in Patient Global Impression of Change (PGIC)	Change in Patient Global Impression of Change (PGIC) after 56 days treatment from 1 to 7 where the higher number indicates a larger improvement.	Day 56
Secondary	Change or reduction in patient average daily NPRS	Change or reduction in patient average daily Numerical Pain Rating Scale (NPRS) after 56 days treatment. NPRS is an 11-point scale from 0 to 10 where the higher number indicates worse pain.; NPRS averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1 Day 56: calculated weekly average from Day 49 to Day 55 for the NPRS	Day 56
Secondary	Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance- Short Form (SF) 8a	Change from baseline (Day 0) in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance - Short Form (SF) 8a after 56 days treatment. PROMIS sleep disturbance is a series of 8 questions, each on a 5-point scale (1-5) where the higher number indicates a worse outcome. A total score out of 40 will be calculated.	Day 56
Secondary	Change in the PROMIS Pain Interference- SF 8a score	Change from baseline (Day 0) in the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference - SF 8a score after 56 days treatment. PROMIS pain interference is a series of 8 questions, each on a 5-point scale (1-5) where the higher number indicates a worse outcome. A total score out of 40 will be calculated.	Day 56
Secondary	Change in the PROMIS General Life Satisfaction- SF 5a	Change from baseline (Day 0) in the Patient-Reported Outcomes Measurement Information System (PROMIS) General Life Satisfaction - SF 5a after 56 days treatment. PROMIS General Life Satisfaction is series of 5 questions, each on a 7-point scale (1-7) where the higher number indicates a better outcome. A total score out of 35 will be calculated.	Day 56
Secondary	Change in the PROMIS Fatigue- SF 8a	Change from Baseline (Day 0) in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue - SF 8a after 56 days treatment. PROMIS Fatigue is a series of 8 questions, each on a 5-point scale (1-5) where the higher number indicates a worse outcome. A total score out of 40 will be calculated.	Day 56
Secondary	Reduction of plasma serum mast cell tryptase, IL-6, and IL-1beta during FSD201 treatment	Determine whether FSD201 treatment reduces serum mast cell tryptase, IL6, and IL-1beta during treatment compared to Day 0	Day 14, Day 28 and Day 56
Secondary	Percentage of subjects achieving =30% reduction in NPRS score	Percentage of subjects achieving =30% reduction in Numerical Pain Rating Scale (NPRS) score. NPRS is an 11-point scale from 0 to10 where the higher number indicates worse pain.; NPRS averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1 Day 28: calculated weekly average from Day 22 to Day 28 Day 56: calculated weekly average from Day 49 to Day 55 for the NPRS	Day 28, Day 56
Secondary	Change in Daily Sleep Interference Scale (DSIS)	Daily Sleep Interference Scale (DSIS) is an 11-point scale (0-10 where the higher number indicates worse ability to sleep.; Averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1 Day 28: calculated weekly average from Day 22 to Day 28 Day 56: calculated weekly average from Day 50 to Day 56 for the DSIS	Day 28, Day 56
Secondary	Change in Patient Global Impression of Change (PGIC)	Change in Patient Global Impression of Change (PGIC) from 1 to 7 where the higher number indicates a larger improvement.	Day 28, Day 56
Secondary	Change in pain intensity on the NPRS from baseline to each week of treatment	Change in pain intensity on the Numerical Pain Rating Scale (NPRS) score from baseline to each week of treatment. NPRS is an 11-point scale from 0 to 10 where the higher number indicates worse pain.; Averages will be calculated as follows: Baseline: calculated weekly average from Day -7 to Day -1; Week 1: calculated weekly average from Day 0 to Day 6; Week 2: calculated weekly average from Day 7 to Day 13; Week 3: calculated weekly average from Day 14 to Day 20; Week 4: weekly average from Day 21 to Day 27; Week 5: calculated weekly average from Day 28 to Day 34; Week 6: calculated weekly average from Day 35 to Day 41; Week 7: calculated weekly average from Day 42 to Day 48; Week 8: calculated weekly average from Day 49 to Day 55	Day 0 to Day 56
Secondary	Percentage of subjects achieving =50% reduction in NPRS	Change from baseline in the weekly average of the average daily pain intensity measured by Numerical Pain Rating Scale (NPRS) score from baseline to each week of treatment. NPRS is an 11-point scale from 0 to 10 where the higher number indicates worse pain.; Baseline: calculated weekly average from Day -7 to Day -1 Day 56: calculated weekly average from Day 49 to Day 55	Week 1 to Week 8
Secondary	Total amount of rescue medication used	Total amount of rescue medication used	Day 0 to Day 56
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the dosing period	Day 0 to Day 56
Secondary	Incidence and severity of treatment-emergent changes in laboratory values	Incidence and severity of treatment-emergent changes in laboratory values at Day 56	Day 56
Secondary	Change from baseline in sitting blood pressure at each in-patient visit	Change from baseline (Day 0) in sitting blood pressure at each in-patient visit	Day 14, Day 28, Day 56
Secondary	Change from baseline in heart rate at each in-patient visit	Change from baseline (Day 0) in heart rate at each in-patient visit	Day 14, Day 28, Day 56
Secondary	Change from baseline in body temperature at each in-patient visit	Change from baseline (Day 0) in body temperature at each in-patient visit	Day 14, Day 28, Day 56
Secondary	Change from baseline in oxygen saturation at each in-patient visit	Change from baseline (Day 0) in oxygen saturation using Pulse oximetry at each in-patient visit	Day 14, Day 28, Day 56
Secondary	Change from baseline in breathing rate at each in-patient visit	Change from baseline (Day 0) in breathing rate at each in-patient visit	Day 14, Day 28, Day 56