SPI-62 for Cushing's Syndrome

(RESCUE Trial)

No longer recruiting at 27 trial locations

Overseen By Frank Czerwiec, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sparrow Pharmaceuticals

Disqualifiers: Recent surgery, Radiation therapy, Adrenalectomy, Pregnancy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of an experimental treatment called SPI-62 for individuals with Cushing's syndrome caused by a non-adrenal tumor. Cushing's syndrome occurs when the body produces too much cortisol, a stress hormone. Participants will take either the active drug or a placebo (a look-alike pill with no active ingredients) for 12 weeks. Those diagnosed with ACTH-dependent Cushing's syndrome and elevated cortisol levels might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that SPI-62 is likely to be safe for humans?

Research shows that SPI-62, a new drug under testing, has promising safety results. Earlier studies found that this drug effectively blocks an enzyme called HSD-1, which helps produce cortisol, a stress hormone, in the liver. In these studies, SPI-62 lowered cortisol levels by 90%.

Although detailed safety information is not yet complete, SPI-62's progression to Phase 2 clinical testing indicates it passed initial safety tests. This suggests it was likely well-tolerated by patients in earlier studies. So far, no specific reports of serious side effects have emerged. However, as with any treatment, monitoring for negative effects is important. Participants should feel free to discuss any concerns with the trial organizers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for Cushing's Syndrome, which often involve surgery or medications that inhibit cortisol production, SPI-62 works by targeting the enzyme 11β-HSD1. This enzyme plays a crucial role in cortisol metabolism, and by inhibiting it, SPI-62 may reduce excess cortisol levels more effectively. Researchers are excited about SPI-62 because it offers a novel mechanism of action that could potentially lead to better control of symptoms with fewer side effects compared to existing therapies.

What evidence suggests that SPI-62 might be an effective treatment for Cushing's syndrome?

Research has shown that SPI-62, which participants in this trial may receive, could be a promising treatment for Cushing's syndrome, particularly when caused by a tumor outside the adrenal glands. SPI-62 blocks an enzyme called HSD-1, reducing cortisol levels inside cells. In earlier studies, SPI-62 lowered cortisol in the liver by 90%. Lowering cortisol can help relieve Cushing's syndrome symptoms. This treatment might provide a new option for managing the condition if other treatments have not been successful. ^{2 3 4 5 6}

Who Is on the Research Team?

Frank Czerwiec, MD

Principal Investigator

Sparrow Pharmaceuticals ([e-mail])

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ACTH-dependent Cushing's syndrome not caused by an adrenal tumor. Participants must have consistent cortisol excess and a confirmed diagnosis. They can't join if they've had recent Cushing's surgery, are at risk of tumor growth complications, have conditions that could affect the study, are pregnant or not using contraception, or have had certain past treatments for Cushing's.

Inclusion Criteria

You have ongoing high levels of cortisol in your body.

I have been diagnosed with ACTH-dependent Cushing's syndrome.

I am a man or a woman who does not have periods.

Exclusion Criteria

I don't have any health issues that would affect this study's process or results.

I have had or will have surgery for Cushing's disease within 6 months.

I have a history of specific adrenal gland surgery or rare forms of Cushing's syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Baseline

Participants undergo baseline assessments before starting treatment

1 week

Treatment

Participants receive either SPI-62 or placebo for 24 weeks

24 weeks

Visits every 3 months, with remote options

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SPI-62

Trial Overview The study tests SPI-62 against a placebo in patients with ACTH-dependent Cushing's syndrome. Each participant will receive both SPI-62 and a placebo for 24 weeks each, with an option to continue longer. The assignment to either SPI-62 or placebo is random.

How Is the Trial Designed?

Group I: SPI-62 Experimental Treatment 2 Interventions

Active drug by mouth each morning for up to 12 weeks

Group II: Placebo Placebo Group 2 Interventions

Placebo by mouth each morning for up to 12 weeks

Who Is Running the Clinical Trial?

Sparrow Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

160+

Published Research Related to This Trial

In a proof-of-concept study involving 12 adult patients with moderate-to-severe Cushing's disease, LCI699 effectively normalized urinary free cortisol (UFC) levels or achieved a significant reduction (≥50%) from baseline after 10 weeks of treatment.

LCI699 was generally well tolerated, with most adverse events being mild or moderate, and no serious drug-related adverse events reported, indicating a favorable safety profile for this potential treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study. Bertagna, X., Pivonello, R., Fleseriu, M., et al.[2022]

Citations

1. sparrowpharma.com sparrowpharma.com/news/sparrow-presents-data-at-european-congress-of-endocrinology

Sparrow Pharmaceuticals Presents Data on SPI-62 at the ... SPI-62, a potent and selective HSD-1 inhibitor, has demonstrated the ability to reduce intracellular cortisol in the liver by 90%.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05307328?cond=Ectopic%20ACTH%20syndrome&rank=9

SPI-62 as a Treatment for Adrenocorticotropic Hormone ... This is a randomized, placebo-controlled, study of SPI-62 in subjects with ACTH-dependent Cushing's syndrome caused by a non-adrenal tumor.

3. biorxiv.org biorxiv.org/content/10.1101/2024.05.27.596076v1.full-text

The 11β-hydroxysteroid dehydrogenase type 1 inhibitor ... The results of this study support potential that SPI-62, or HSD-1 inhibitors in general, might alleviate certain symptoms of Cushing's disease ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20537220

SPI-62 as a Treatment for Adrenocorticotropic Hormone ... SPI-62 has the potential to reduce symptoms associated with Cushing's syndrome by possibly reducing the amount of cortisol inside cells in different parts of ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-spi-62-for-treating-acth-dependent-cushings-syndrome-in-patients-with-cushings-disease-or-ectopic-acth-crh-secretion/

Study of SPI-62 for Treating ACTH-Dependent Cushing's ... This study investigates the efficacy of SPI-62, an enzyme inhibiting drug, for the treatment of ACTH-Dependent Cushing's Syndrome, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05307328

Study Details | NCT05307328 | SPI-62 as a Treatment for ... This is a multicenter, randomized, placebo-controlled, Phase 2 study to evaluate the pharmacologic effect, efficacy, and safety of SPI-62 in subjects with ACTH ...