Protocol A Proof-of-concept Study to Evaluate the Efficacy and Safety of Rozanolixizumab to Treat [Adults] With Severe Fibromyalgia Syndrome, 2022-4, UK

https://classic.clinicaltrials.gov/...df&type=Intr&cond=Fibromyalgia&draw=3&rank=11

Recruitment Status : Recruiting
Actual Study Start Date : December 21, 2022
Estimated Primary Completion Date : September 11, 2024
Estimated Study Completion Date : September 11, 2024

Experimental: Treatment sequence 1
Study participants on Treatment sequence 1 will receive rozanolixizumab and Placebo during the dosing period at pre-specified timepoints.
Experimental: Treatment sequence 2
Study participants on Treatment sequence 2 will receive rozanolixizumab and Placebo during the dosing period at pre-specified timepoints.
Placebo Comparator: Treatment sequence 3
Study participants on Treatment sequence 3 will receive Placebo during the dosing period at pre-specified timepoints.

Primary Outcome Measures :
  1. Brief Pain Inventory short form (BPI-SF) average interference score after 12 weeks of treatment [ Time Frame: After 12 weeks of treatment ]
    The short form of the BPI is a self-administered questionnaire used to evaluate the severity of a study participant's pain and the impact of this pain on the study participant's daily functioning. The BPI-SF assesses for the location of pain, pain intensity and functional interference from pain. The 7 BPI-SF interference items include: general activity, mood, walking ability, normal work (including housework), relations with other people, sleep, and enjoyment of life. Each item is rated on a 0 (does not interfere) to 10 (completely interferes) scale with a recall period of 24 hours. The arithmetic mean of the 7 interference items can be used as a measure of pain interference.

Locations
United Kingdom: Recruiting in Blackpool, Liverpool, Manchester, Stockton-on-tees, Tankersley,
Sponsors and Collaborators
UCB Biopharma SRL
Investigators
Study Director: UCB Cares
 
60 participant; quadruple blinding

Secondary outcomes
  • Percentage of participants with treatment-emergent adverse events (TEAEs) during the study [ Time Frame: From Baseline till end of Safety Follow-up (up to 32 Weeks) ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.
  • Percentage of participants with TEAEs leading to withdrawal of investigational medicinal product (IMP) [ Time Frame: From Baseline till end of Safety Follow-up (up to 32 Weeks) ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.
  • Brief Pain Inventory short form (BPI-SF) average interference score after 24 weeks of treatment [ Time Frame: After 24 weeks of treatment ]
    The short form of the BPI is a self-administered questionnaire used to evaluate the severity of a study participant's pain and the impact of this pain on the study participant's daily functioning. The BPI-SF assesses for the location of pain, pain intensity and functional interference from pain. The 7 BPI-SF interference items include: general activity, mood, walking ability, normal work (including housework), relations with other people, sleep, and enjoyment of life. Each item is rated on a 0 (does not interfere) to 10 (completely interferes) scale with a recall period of 24 hours. The arithmetic mean of the 7 interference items can be used as a measure of pain interference.
  • Revised Fibromyalgia Impact Questionnaire (FIQR) score after 10 weeks of treatment [ Time Frame: After 10 weeks of treatment ]
    The Revised Fibromyalgia Impact Questionnaire (FIQR) is a 21-item questionnaire with a recall period of 7 days. The FIQR includes 3 domains: function, overall impact, and symptoms. Each item is based on an 11-point numeric rating scale. The total score ranges from 0 to 100, with 0 denoting the best possible condition and 100 denoting the worst possible condition.
  • Mean 7-day average daily pain score assessed with Pain Numeric Rating Scale after 10 weeks of treatment [ Time Frame: After 10 weeks of treatment ]
    The Pain Numeric Rating Scale (NRS) is a numeric version of the Visual Analogue Scale (VAS) in which a respondent selects a whole number that best describes "How much pain have you experienced on average over the past 24 hours?" The 11-point Pain NRS ranges from 0 (no pain) to 10 (pain as bad as you can imagine).
  • Mean 7-day fatigue score assessed with Fatigue Numeric Rating Scale after 10 weeks of treatment [ Time Frame: After 10 weeks of treatment ]
    The Fatigue Numeric Rating Scale (NRS) is a numeric version of the Visual Analogue Scale (VAS) in which a respondent selects a whole number that best describes "How much fatigue have you experienced on average over the past 24 hours?" The 11-point Fatigue NRS ranges from 0 (no fatigue) to 10 (fatigue as bad as you can imagine).
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I don't fully understand the rationale of the primary outcome. It's just seven questions on how much pain interferes with function, taken out of a larger questionnaire (the Brief Pain Inventory) that includes questions specifically on pain, at 12 weeks. If this was a BPS study, I would understand the rationale, as the idea would be that it doesn't matter if the person still thinks they have pain, what's important is to what extent they can ignore it in order to function. But here, it seems an odd measure to focus on. There is a secondary measure that looks at pain, but it is taken at 10 weeks. There is a Fibromyalgia Impact Questionnaire with 21 questions covering function, overall impact and symptoms which sounds good, but that is only a secondary outcome, measured at 10 weeks.

In terms of longer term effect, again it's just the pain interference measure at 24 weeks.

There aren't any objective measures, which seems surprising and provides no protection against the possibility that the nature of the treatment will make it easy for the blinding to be broken. I would have thought there would be regular blood tests, maybe to track levels of the antibodies, maybe to check for liver damage or something. I suppose not having any blood testing keeps costs down.
 
Hutan said:
60 participant; quadruple blinding

Secondary outcomes


I don't fully understand the rationale of the primary outcome. It's just seven questions on how much pain interferes with function, taken out of a larger questionnaire (the Brief Pain Inventory) that includes questions specifically on pain, at 12 weeks. If this was a BPS study, I would understand the rationale, as the idea would be that it doesn't matter if the person still thinks they have pain, what's important is to what extent they can ignore it in order to function. But here, it seems an odd measure to focus on. There is a secondary measure that looks at pain, but it is taken at 10 weeks. There is a Fibromyalgia Impact Questionnaire with 21 questions covering function, overall impact and symptoms which sounds good, but that is only a secondary outcome, measured at 10 weeks.

In terms of longer term effect, again it's just the pain interference measure at 24 weeks.

There aren't any objective measures, which seems surprising and provides no protection against the possibility that the nature of the treatment will make it easy for the blinding to be broken. I would have thought there would be regular blood tests, maybe to track levels of the antibodies, maybe to check for liver damage or something. I suppose not having any blood testing keeps costs down.
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I didn't quite think it that far, did Goebel paper provide a way to check levels of antibodies?

Also see the MG study, same thing no objective measure but a measure of daily activity
https://classic.clinicaltrials.gov/ct2/show/NCT03971422
 
The drug rozanolixizumab has been FDA approved for myasthenia gravis for improvement in symptoms. The trade name is Rystiggo.

During the trial for MG, the dose was delivered sub-cutaneously. I don't know what the dose range will be for the FM trial.
However, there were adverse events in the MG trial. These include aseptic meningitis, serious infections at 4% of participants (including some pneumonia deaths, some due to covid).

Prescribing info from UCB: https://www.ucb-usa.com/RYSTIGGO-prescribing-information.pdf

As for assessing a decrease or no change in FM pain and fatigue, I would have to invent a software program and run it daily on a participant and graph the results (which vary highly day to day, week to week).
 
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Haven't read above ---!

I assume myasthenia gravis is an autoimmune disease (acetylcholine receptor auto-antibody)? If this drug worked on myasthenia gravis then the assumption is that some/all fibromyalgia is an autoimmune disease? Auto-antibody target in fibromyalgia?

Interesting if it works, but do they have objective outcome measurements [like measuring a biomarker ---] --- guess it's blinded, so that would go some way to assist i.e. if the outcome measurements are not objective.

EDIT - I assume the drugs main advantage is that it's "safe and well-tolerated" i.e. compared to other autoimmune drugs/treatments?
https://link.springer.com/article/1...r (FcRn,degradation, leading to IgG depletion.
 
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The primary outcome was the Brief Pain Inventory Short Form (BPI-SF). The results show 41 participants analyzed in both groups with the following means:

Placebo: 6.30 (5.59 to 7.01)
RLZ: 5.76 (5.11 to 6.41)
 
Using the CI of the means, I've tried to calculate the mean difference and its confidence interval and p-value.

I got: 0.54 (-0.42, 1.50), p-value = 0.26.

So it seems like the difference was not statistically significant and might be due to random variation.
 
Participant flow:
A. 22 participants in the 24 week treatment - 17 completed, 2 lost due to adverse events
B. 20 participants in the 12 week placebo, 12 week treatment group - 18 completed, 0 lost due to adverse events
C. 21 participants in the 24 week placebo - 20 completed, 1 lost due to adverse event

Outcome measures
Brief Pain Inventory Short Form - 12 weeks
The BPI-SF was a self-administered questionnaire used to evaluate the severity of a study participant's pain and the impact of this pain on the study participant's daily functioning. The BPI-SF assesses for the location of pain, pain intensity and functional interference from pain. The 7 BPI-SF interference items included: general activity, mood, walking ability, normal work (including housework), relations with other people, sleep, and enjoyment of life. Each item was rated on a 0 (did not interfere) to 10 (completely interfere) scale with a recall period of 24 hours. The BPI-SF interference score ranges 0-70. Higher scores indicated greater interference.
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Placebo: 6.30 (5.59 to 7.01)
RLZ: 5.76 (5.11 to 6.41)

It's not clear what those numbers mean (I think they are the mean score, averaged over the 7 items, as opposed to a mean difference from baseline out of 70). It's also not clear how they treated the different lengths of time on the treatment. I mean, when did they take the outcome?
"Participants who received 12 weeks of RLZ 560 mg SC treatment during any sequence."
"Participants received a [placebo] exposure up to 12 weeks and/or extended exposure from 12 to 24 weeks."

The p value of the test for a difference between treatment and placebo seems to be 0.129. (given in Statistical Analysis 1)

So, regardless of the uncertainties about scoring and the time point, there was no significant difference between treatments.
 
Another questionnaire, The Revised Fibromyalgia Impact Questionnaire (FIQR, range 0-100), did show a significant difference between groups.

The RLZ has a score of 62.3 (57.32 to 67.28) compared to 70.70 (64.90 to 76.50) in the control group, with lower scores being better. The p-value of the mixed-effects model was 0.003.
 
ME/CFS Skeptic said:
Another questionnaire, The Revised Fibromyalgia Impact Questionnaire (FIQR, range 0-100), did show a significant difference between groups.

The RLZ has a score of 62.3 (57.32 to 67.28) compared to 70.70 (64.90 to 76.50) in the control group, with lower scores being better. The p-value of the mixed-effects model was 0.003.
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Yes, this is the above significance metric the UCB press release talked about.

Paper should be out later this year.
 
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