CC-99677 for Ankylosing Spondylitis

(AS SpA axSpA Trial)

No longer recruiting at 156 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celgene

Must not be taking: Cell depleting biologics, Corticosteroids

Disqualifiers: Total spine ankylosis, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of the new treatment, CC-99677, for individuals with active Ankylosing Spondylitis (AS), a type of arthritis primarily affecting the spine. Researchers seek to determine if this treatment can improve symptoms, reduce disease activity, and enhance overall quality of life compared to a placebo (a substance with no active drug). The study includes various groups, such as those who have not previously tried biologic treatments and those who have. Suitable candidates have AS with ongoing symptoms, have tried at least two non-steroidal treatments without success, and either have not used biologic treatments or have tried more than one. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in AS treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on certain treatments like cell depleting biologic agents within 6 months before starting the trial, or high doses of oral corticosteroids for more than 2 weeks before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that CC-99677 is safe and well-tolerated in healthy volunteers. Research indicates that the treatment behaves predictably in the body. No major safety issues were reported, and the treatment demonstrated positive safety results.

Since this study is in an early phase, some evidence of safety exists, but more data will be collected over time to confirm how well participants tolerate the treatment. This stage aims to further explore safety in people with Ankylosing Spondylitis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AS?

Researchers are excited about CC-99677 for ankylosing spondylitis because it offers a novel approach compared to current treatments like NSAIDs, TNF inhibitors, and IL-17 inhibitors. Unlike those treatments, CC-99677 is a small molecule inhibitor that targets the protein TYK2, which plays a crucial role in the inflammatory process. This new mechanism of action could potentially provide relief with fewer side effects and greater convenience, as it is taken orally. Additionally, CC-99677 offers different dosing options, allowing for flexible treatment strategies tailored to individual needs.

What evidence suggests that CC-99677 might be an effective treatment for Ankylosing Spondylitis?

Studies have shown that CC-99677 is a promising new treatment for ankylosing spondylitis (AS). It targets a specific part of the inflammation process involved in AS. In animal studies, CC-99677 effectively reduced symptoms, suggesting it might help manage AS in humans. Early research from other inflammatory disease studies indicates it is safe and well-tolerated at different doses. Although more research in humans is needed, these findings suggest CC-99677 could potentially improve AS symptoms by reducing inflammation. Participants in this trial will receive either CC-99677 at varying doses or a placebo, allowing researchers to evaluate its effectiveness and safety in treating AS. ^{3 5 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb, MD

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Inclusion Criteria

Ankylosing spondylitis is a rheumatic disease that principally affects the spine

Spondylitis Disease Activity Score (BASDAI) of ≥4 If someone has an active axial disease at both the time of their screening and baseline visits, then their Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) must be 4 or higher in order for them to be considered to have active axial disease.

A person has spondylitis if their BASDAI score is ≥ 4 and their total back pain is ≥ 4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CC-99677 or placebo to evaluate efficacy and safety in treating Ankylosing Spondylitis over a 12-week double-blind period

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CC-99677
• Placebo

How Is the Trial Designed?

Group I: Administration of CC-99677 60mg QD PO. Experimental Treatment 1 Intervention

20 participants will be randomized to CC-99677 60 mg in biologic-failure substudy

Group II: Administration of CC-99677 60mg QD PO Experimental Treatment 1 Intervention

49 participants will be randomized to CC-99677 60 mg in biologic naive main study

Group III: Administration of CC-99677 150 mg QD PO. Experimental Treatment 1 Intervention

20 participants will be randomized to CC-99677 150 mg in biologic-failure substudy

Group IV: Administration of CC-99677 150 mg QD PO Experimental Treatment 1 Intervention

49 participants will be randomized to CC-99677 150 mg in biologic naive main study

Group V: Placebo additional dose cohort Placebo Group 1 Intervention

10 participants will be randomized to placebo in biologic-failure substudy

Group VI: Administration of Placebo QD PO Placebo Group 1 Intervention

49 participants will be randomized to placebo in biologic naive main study

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

A review of 192 randomized clinical trials revealed that safety information is often underreported, with only 46% specifying reasons for withdrawals due to toxicity and only 39% adequately reporting clinical adverse effects.

To enhance safety reporting, the study emphasizes the need for standardized scales for adverse effects, systematic data collection, and detailed reporting of severe reactions, suggesting that improved practices could lead to better safety insights in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. Ioannidis, JP., Lau, J.[2018]

In a review of 231 randomized placebo-controlled clinical trials, it was found that a staggering 96.8% of adverse events (AEs) reported in patients taking active drugs were nonspecific, meaning they were not directly related to the medication.

The study revealed strong correlations between AE rates in placebo and active-drug groups, indicating that many reported AEs may not be caused by the drug itself, which raises concerns about the reliability of clinical trial data in assessing drug tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials. Mahr, A., Golmard, C., Pham, E., et al.[2022]

The study analyzed adverse event (AE) data from six randomized controlled trials involving schizophrenia treatments, highlighting that the absolute prevalence and expected duration of AEs provide a more comprehensive understanding of a drug's safety compared to just incidence rates.

Using a new metric to assess the drug-placebo difference in AE prevalence, the research found that some AEs not listed in the standard drug label significantly impacted drug tolerability, suggesting that including these metrics in drug labels could enhance safety signal detection and inform better treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Method for Deriving Adverse Event Prevalence in Randomized Controlled Trials: Potential for Improved Understanding of Benefit-Risk Ratio and Application to Drug Labels. Piacentino, D., Ogirala, A., Lew, R., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9386913/

CC-99677, a novel, oral, selective covalent MK2 inhibitor ... CC-99677 is a novel, irreversible, covalent MK2 inhibitor under development for the treatment of ankylosing spondylitis (AS) and other inflammatory diseases.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1931524422001384

Discovery of CC-99677, a selective targeted covalent ... CC-99677 is a selective, potent, covalent MK2 inhibitor, a downstream target of p38, that showed efficacy in a rat model of ankylosing spondylitis.

3. the-rheumatologist.org the-rheumatologist.org/article/early-data-on-novel-mk2-inhibitor-to-treat-inflammatory-diseases-promising/

Early Data on Novel MK2 Inhibitor to Treat Inflammatory ... The primary study outcome was the safety and tolerability of multiple daily doses of CC-99677. The study's secondary and exploratory outcomes ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04947579

A Study of CC-99677 in Participants With Active Ankylosing ... This study is designed to learn about response to CC-99677 treatment by measuring signs and symptoms of Ankylosing Spondylitis (AS), objective measures of ...

5. acrabstracts.org acrabstracts.org/abstract/cc-99677-a-novel-selective-oral-mk2-inhibitor-sustainably-reduces-pro-inflammatory-cytokine-production-and-ameliorates-inflammation-in-the-mannan-induced-murine-model-of-psoriasis-and-psoriatic-ar/

CC-99677, a Novel, Selective, Oral MK2 Inhibitor ... CC-99677 reduced the PsASI score in a dose-dependent manner. Results: In the in vitro model of tachyphylaxis, CC-99677 and p38 inhibitors similarly decreased ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03554993

NCT03554993 | A Study to Evaluate the Safety, Tolerability ... This first-in-human (FIH) study aims to identify a safe and tolerable dose of CC 99677 in support of phase 2 and/or phase 3 studies to be conducted in subjects ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35982464/

CC-99677, a novel, oral, selective covalent MK2 inhibitor ... Administration of CC-99677 to healthy volunteers was safe and well-tolerated, with linear pharmacokinetics and sustained reduction of ex ...

8. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/safety-tolerability-pk-and-pd-of-cc-99677-in-healthy-subjects/

Safety, Tolerability, PK and PD of CC-99677 in Healthy ... Part 2 will begin only once a review of safety and PK data from the first 3 dose levels in Part 1 has determined it safe to do so. In both Parts, administration ...