Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway

Rhythm Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: POMC Deficiency; Bardet-Biedl Syndrome

Treatments: Drug: Setmelanotide 20 mg; Drug: Setmelanotide 25 mg; Drug: Setmelanotide 30 mg; Drug: Setmelanotide 2.5 mg; Drug: Setmelanotide 2 mg; Drug: Setmelanotide 3 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05194124

RM-493-037

Details and patient eligibility

About

A trial to compare the weekly and daily formulations of setmelanotide in participants with genetic defects in the melanocortin-4 receptor pathway.

Full description

This study is designed to compare the safety, pharmacokinetics, and efficacy of weekly and daily formulations of setmelanotide in participants with obesity associated with biallelic or heterozygous POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin Type 1), LEPR (leptin receptor) genetic variants, and participants with Bardet-Biedl Syndrome (BBS).

Enrollment: 19 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Biallelic or heterozygous POMC/PCSK1 or LEPR (PPL) genetic variants or Bardet-Biedl syndrome (BBS), for which they are being treated with QD setmelanotide.
• 6 years or older at screening.
• Taking the setmelanotide QD formulation for at least 6 months in the RM-493-022 (NCT03013543) study with acceptable safety and tolerability, and dose level.
• Participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent.
• Use of a highly effective form of contraception throughout the study and for 90 days following the study.

Key Exclusion Criteria:

• Glycosylated hemoglobin (HbA1C) >9.0% at screening.
• Anti-obesity medications within 3 months prior to starting the Run-in Period.
• History of significant liver disease or liver injury.
• Glomerular filtration rate <30 milliliter per minute (mL/min).
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
• Major psychiatric disorders.
• Any suicidal ideation or behavior, or any lifetime history of a suicide attempt.
• Significant hypersensitivity to any excipient in the study drug.
• Inability to comply with the QW and QD injection regimens.
• Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing, with the exception of a setmelanotide clinical trial.

Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

19 participants in 10 patient groups

Run-in Period: Setmelanotide 2 mg QD

Experimental group

Description:

Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period.

Treatment:

Drug: Setmelanotide 2 mg

Run-in Period: Setmelanotide 2.5 mg QD

Experimental group

Description:

Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.

Treatment:

Drug: Setmelanotide 2.5 mg

Run-in Period: Setmelanotide 3 mg QD

Experimental group

Description:

Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.

Treatment:

Drug: Setmelanotide 3 mg

DB Period: Setmelanotide 20 mg QW

Experimental group

Description:

Participants who received 2 mg setmelanotide QD in the run-in period, received SC injection of 20 mg setmelanotide once weekly (QW) and placebo matched to setmelanotide QD for 13 weeks in the DB period.

Treatment:

Drug: Setmelanotide 20 mg

DB Period: Setmelanotide 25 mg QW

Experimental group

Description:

Participants who received 2.5 mg setmelanotide QD in the run-in period, received SC injection of 25 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.

Treatment:

Drug: Setmelanotide 25 mg

DB Period: Setmelanotide 3 mg QD

Experimental group

Description:

Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 3 mg setmelanotide QD and placebo matched to setmelanotide QW for 13 weeks in the DB period.

Treatment:

Drug: Setmelanotide 3 mg

DB Period: Setmelanotide 30 mg QW

Experimental group

Description:

Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 30 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.

Treatment:

Drug: Setmelanotide 30 mg

OL Period: Setmelanotide 20 mg QW

Experimental group

Description:

Participants who received 2 mg setmelanotide QD in the run-in period and 20 mg setmelanotide QW in the DB period, received SC injection of 20 mg setmelanotide QW for 13 weeks in the OL period.

Treatment:

Drug: Setmelanotide 20 mg

OL Period: Setmelanotide 25 mg QW

Experimental group

Description:

Participants who received 2.5 mg setmelanotide QD in the run-in period and 25 mg setmelanotide QW in the DB period, received SC injection of 25 mg setmelanotide QW for 13 weeks in the OL period.

Treatment:

Drug: Setmelanotide 25 mg

OL Period: Setmelanotide 30 mg QW

Experimental group

Description:

Participants who received 3 setmelanotide QD in the run-in period and 3 mg setmelanotide QD or 30 mg setmelanotide QW in the DB period, received SC injection of 30 mg setmelanotide QW for 13 weeks in the OL period.

Treatment:

Drug: Setmelanotide 30 mg