ARA-290 / Cibinetide

01 / Dosing schedule

Cited dosing

ARA-290 has two distinct published human regimens from placebo-controlled phase 2 trials: 2 mg intravenously three times weekly for 4 weeks, and 4 mg subcutaneously once daily for 28 days. It is not FDA approved.

ARA-290 (cibinetide) phase 2 regimens

Phase	Dose & frequency
Sarcoidosis trial, IV	2 mg intravenously, three times weekly (Mon/Wed/Fri), for 4 consecutive weeks; infused over 2 min in 6 mL normal saline
Sarcoidosis trial, weight-normalised	24.6 +/- 1.1 microg/kg; 997.1 +/- 26.9 microg/m2
Type 2 diabetes trial, subQ	4 mg subcutaneously once daily for 28 days, then 28 days of observation without treatment
Type 2 diabetes trial, weight-normalised	45.0 +/- 1.9 microg/kg; 1.9 +/- 0.05 mg/m2; 0.5 cc injection volume
Dose-ranging PK in volunteers	2 mg IV and 2, 4 and 6 mg subQ in a 10-volunteer crossover study
Prior open-label human dosing	2 mg IV, three doses every 2 days over 1 week

Source · Dahan A, Dunne A, Swartjes M, et al. ARA 290 Improves Symptoms in Patients with Sarcoidosis-Associated Small Nerve Fiber Loss and Increases Corneal Nerve Fiber Density. Mol Med / and Brines M et al. ARA 290, a Nonerythropoietic Peptide Engineered from Erythropoietin, Improves Metabolic Control and Neuropathic Symptoms in Patients with Type 2 Diabetes. ↗

Source indication · Small-fibre neuropathy: sarcoidosis-associated small nerve fibre loss with neuropathic pain, and painful small-fibre neuropathy in type 2 diabetes (Araim phase 2 trials)

Injection frequency: Either 2 mg IV three times weekly for 4 weeks, or 4 mg subQ once daily for 28 days, depending on the trial.
Injection sites: Reported in the trials: subcutaneous injections into the anterior thigh with rotating injection sites (type 2 diabetes trial); 'the site of the injection into the upper leg or lower abdomen' (sarcoidosis follow-on trial). IV dosing in the sarcoidosis trial was given in an outpatient anaesthesiology clinic.

02 / Reconstitution

Reconstitution reference

The sarcoidosis trial infused ARA 290 in 6 mL normal saline over 2 minutes. The subcutaneous trials used a 0.5 cc injection volume; the matching placebo vehicle was 20 mmol/L sodium phosphate buffer pH 6.5 with 1% sucrose and 4% D-mannitol.

Vialn.a. — trial-supplied product; vial size not published

BAC water6 mL normal saline for the 2 mg IV dose (trial procedure)

Concentrationn.a.

Example dose4 mg subcutaneously once daily (type 2 diabetes trial)

On a U‑100 syringe0.5 cc total injection volume per trial protocol

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03 / Overview

Protocol overview

ARA-290 (cibinetide) is an 11-amino-acid peptide derived from the helix-B surface of erythropoietin. It engages the innate repair receptor without stimulating erythropoiesis, and its terminal half-life after a 4 mg subcutaneous dose in normal volunteers is approximately 20 minutes — far shorter than its pharmacodynamic effect.

In the randomized sarcoidosis trial, patients with sarcoidosis-associated small nerve fibre loss received 2 mg ARA 290 intravenously on Mondays, Wednesdays and Fridays for four consecutive weeks (n=12 in the dosed arm of the reported cohort), each dose infused over 2 minutes in 6 mL saline, with 60 minutes of post-infusion monitoring.

A larger 38-patient placebo-controlled sarcoidosis study then moved to 4 mg subcutaneously daily for 28 days, chosen after a 10-volunteer crossover PK comparison of 2 mg IV against 2, 4 and 6 mg subcutaneous. Follow-up ran 12 weeks after dosing, with questionnaires to 16 weeks and again about 9 months after the end of dosing.

The type 2 diabetes trial used the same 4 mg daily subcutaneous dose for 28 days followed by a treatment-free month, with self-injection into the anterior thigh at rotating sites. One participant stopped on day 15 for worsening borderline renal insufficiency. All of this is phase 2 evidence; there is no approved cibinetide product.

04 / References